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NCTID
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NCT00005780
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Alternatives
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Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not **Take Part In This Study?**
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It should be emphasized that we do not know at this point whether the EPOCH-R and vaccination we propose to give you is superior, inferior, or equivalent to standard combination chemotherapy for your disease. Alternative procedures that could be used to treat your disease include:
- Other combination drug regimens and other schedules of the same drugs used in this study. For example, a chemotherapy called CHOP given in the conventional manner
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 00-C-0133 CONTINUATION: page 11 of 15 pages would be suitable standard therapy for your condition. You could also receive EPOCH-R as standard treatment.
- Treatment with single drugs. This is known to produce brief responses of a few months' duration in many patients but to have little beneficial effect in long-term control of the disease.
- Radiation (X-ray) treatments. This can stop tumor growth in particular locations, such as bone, abdomen, and other sites but is not successful in controlling the disease overall unless the disease is very localized at the start of therapy.
- Surgery. As with radiation, surgery can be successful in removing tumor from particular locations but cannot be used successfully to remove all lymphoma cells from the body, since the disease is almost always present in multiple locations. Also, surgery cannot be used against tumor in some of the organs most commonly involved by lymphoma, such as the liver or the lungs.
- Waiting, without active therapy. Although a period of watchful waiting is appropriate treatment for some kinds of tumors, in lymphomas similar to yours the disease will often grow and spread rapidly if no treatment is administered.
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NCT00005780
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Confidentiality
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Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality
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We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 00-C-0133 CONTINUATION: page 12 of 15 pages
- The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.
- National Cancer Institute Institutional Review Board
- Some of the specimens and/or data obtained may be sent to researchers outside of the National Cancer Institute to perform additional research studies designed to help us better understand lymphoma.
- Biovest International, Inc. will have limited access to the clinical data and results in NIH's possession and control as needed to support the registration of the Id-KLH Vaccine by the FDA in this disease.
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most the Web site will include a summary of the results. You can search this Web site at any time.
To help us protect your privacy, we have obtained a Certificate of Confidentiality. The researchers can use this Certificate to legally refuse to disclose information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist any demands for information that would identify you, except as explained below. You should also know that there are several circumstances in which the Certificate does not provide coverage. These include when information:
- will be used for auditing or program evaluation internally by the NIH; or - must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA).
- is necessary for your medical treatment and you have consented to this disclosure;
- is for other research.
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible as evidence or used for any purpose in any action, suit, or proceeding without your consent. You should understand that a Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this research. If an insurer, employer, or other person obtains your written consent to receive research information, then the researchers will not use the Certificate to withhold that information.
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 00-C-0133 CONTINUATION: page 13 of 15 pages The Certificate of Confidentiality will not protect against the required reporting by hospital staff of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others.
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NCT00005780
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Duration of Study Involvement
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What Happens After Treatment Is Completed
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This depends on how you have responded to the therapy. If all evidence of disease has disappeared, we will schedule periodic visits to the Clinical Center for follow-up examination
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 00-C-0133 CONTINUATION: page 6 of 15 pages and tests. If the disease does not disappear entirely or if it should recur after having disappeared for a period of time, then you may need further therapy. At that time you will be given the opportunity of participating in additional research protocols that may be appropriate for you. If no such protocols are available, you will be returned to the care of your local physician. It is important to stress that participation in this protocol does not constitute a promise of long-term medical care here at the Clinical Center. It is conceivable that participation in this study may make you ineligible to participate in certain other research protocols because the requirements for entry onto these protocols may not allow patients who have already been treated with certain drugs or who have had certain side effects from previous treatment. You may decide now not to receive treatment on this protocol, or you may choose at any point in time to stop the treatment and withdraw from the protocol; in either case you will be returned to the care of your referring physician.
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NCT00005780
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Participant's Rights
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Research Subject'S Rights What Are The Costs Of Taking Part In This Study?
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If you choose to take part in the study, the following will apply, in keeping with the NIH policy:
- You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH
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NCT00005780
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Possible Risks, Discomforts, and Inconveniences
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Risks Or Discomforts Of Participation|Psychological Or Social Risks Associated With Loss Of Privacy|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?
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In order to determine whether this study is suitable for you, a number of tests will have to be done. This period of evaluation may take up to two weeks and is usually done on an outpatient basis. Some or all of these tests will be repeated during and after the chemotherapy and vaccine at different times. Depending on the tests you had before coming here, these may include blood and urine tests, studies of lung function, CAT or MRI scans, colonoscopy with biopsies, radioisotope scans, and biopsies of tumor tissue, bone marrow, liver, or other sites. Biopsies will, when possible, be done under local anesthesia. The risks associated with bone marrow biopsies include pain, bleeding, and local infection. Risks of biopsies include pain, bleeding, infection, and the risks to the particular area undergoing surgery. General anesthesia itself is generally very safe but has a very small risk of major complications such as heart attack or stroke. The surgical and anesthetic risks will be explained to you in more detail at the time of surgery, if this is needed. Risks of colonoscopy with biopsies include discomfort and bleeding from the rectum; rarely the colon may be punctured and if this occurs, it is serious and may require surgery. A separate consent describing all of the complications and side effects of colonoscopy with biopsies will be obtained from you. In order to receive this therapy, you will need to have an intravenous catheter placed. This catheter is usually placed in the arm, chest or neck area into a major vein inside your chest. We usually remove the catheter after each cycle but on occasion it can be left in for several cycles. The catheter is necessary for infusion of chemotherapy and for the drawing of blood. It is usually inserted under local anesthesia. The risks associated with the procedure include pain, bleeding, infection, and puncture of the underlying lung. Lung puncture can result in lung collapse, which might require that a chest tube be placed into the chest cavity (usually for a day or two) to help the lung reinflate. The long-term risks of the catheter include infection and clotting of the vein in which the catheter sits. If these occur, it may be necessary to remove the catheter. These risks will be explained to you in more detail at the time of the insertion. The apheresis requires the insertion of an intravenous line in to the arm or chest and peripheral blood STUDY NUMBER: 00-C-0133 CONTINUATION: page 7 of 15 pages will be removed and passed through an apheresis machine; this machine allows us to collect immune cells for research, and to return your own red blood cells and platelets back in your intravenous line. In some patients, we may also collect tumor cells by apheresis to produce the vaccine. Serious reactions associated with apheresis are rare and generally mild. They include pain and bruising at the insertion site of the intravenous line, and a temporary decrease in the platelet count and/or hemoglobin levels. Fainting episodes related to needle insertion can occur, and skin tingling caused by low calcium levels can rarely occur. During the leukopheresis, at least two apheresis nurses will be present, and a blood bank physician will be available in the clinic area where the procedure is performed. For this study, the procedure will typically take about 60 to 90 minutes. Side effects that have been observed with the drugs in this program when they are used individually include the following:
- Doxorubicin may cause sore mouth, loss of hair, a fall in blood counts with increased risk of serious infection or internal bleeding, tissue damage if the drug contacts the skin, heart damage and, rarely, death due to heart failure. However, the infusion method used in this study has been shown to reduce the risk of heart damage.
- Cyclophosphamide may cause a fall in blood counts with increased risk of serious infection or bleeding, loss of hair, damage to the lining of the urinary bladder with painful and bloody urination, loss of function of the ovaries or testes, and nausea and vomiting. Bladder irritation can be minimized by drinking at least two quarts of fluid each day.
- Vincristine often causes numbness of the hands and feet after several cycles. Rarely, patients may develop pain and/or weakness of the foot muscles. Patients also may have constipation and medications will be given to reduce this. In most instances, these symptoms resolve when the drug is stopped, but resolution of the numbness in the hands and feet may sometimes take months or even years. The drug can also cause tissue damage if it contacts the skin.
- Etoposide may cause nausea and vomiting, diarrhea, loss of hair, lowering of blood pressure during administration, mouth ulcers, and lowering of blood counts.
- Rituximab commonly causes fever, chills, nausea, headache, swelling, itchiness and rash.
Low white blood counts may occur but are less common. Occasionally patients have developed low blood pressure, wheezing and rashes during administration of rituximab. Less common toxicities are abdominal pain, vomiting, low platelets and red cells, muscle and joint pains, dizziness and runny nose. Rarely, patients may die from the effects of rituximab due to an allergic reaction or lung problems.
- Prednisone may cause ulceration in the stomach or bowel, increased blood pressure, high blood sugar (diabetes), increased risk of infection, a round appearance of your face, weight gain, change in mood, thinning of your bones with increase in the risk of fracture. It can also cause or worsen acne.
STUDY NUMBER: 00-C-0133 CONTINUATION: page 8 of 15 pages
- G-CSF can occasionally cause bone pain by stimulating normal bone marrow. This stops when drug administration stops. It has also been reported sometimes to cause skin rash, skin reddening around the injection site, muscle cramps, decreased platelets (not clinically significant), pain or numbness and tingling around the chin, worsening of certain pre-existing inflammatory conditions (such as psoriasis, eczema, or vasculitis), fever, body aches, and alterations in certain laboratory tests. With prolonged administration G-CSF has been associated with hair thinning and enlargement of the spleen.
- Vaccine treatment may produce some discomfort, such as redness, swelling and tenderness at the injection site. Fever, chills, rash and flu-like symptoms may also occur. All of these are usually temporary. Although very unlikely, it is possible that you could have a severe allergic reaction with shortness of breath and low blood pressure.
- GM-CSF may cause fever, chills, sweating, muscle aches, tiredness, headache, dizziness, shortness of breath, fluid collection in the lining of the lung, lack of appetite, indigestion, nausea, vomiting, diarrhea, tenderness at the site of injection, hives, rash itching, allergic reactions, bone pain, clotting of blood vessels, low blood pressure, leg swelling, elevated white blood count, elevated platelet count, low platelet count, and abnormal blood tests of the liver.
- Trimethoprim/sulfamethoxazole can cause a skin rash that goes away when the drug is stopped. Inhaled pentamidine can cause coughing, wheezing, and burning pain in the throat. All of these symptoms usually go away shortly after the inhalation treatment is finished.
It is important to emphasize that when you have a decreased white blood cell count from the EPOCH-R treatment, you are at risk of infection. Such infections can be very serious and can even cause death if not quickly and properly treated. Therefore, if you have a temperature greater than 38.3o C (101o F), you must call your doctor immediately. Chemotherapy may also cause your platelets to fall; since platelets are the blood elements that permit blood to clot, this may place you at increased risk of serious bleeding. It may be necessary to give you transfusions of platelets if your platelet counts reach very low levels. There is a small chance that damage to the normal bone marrow may eventually result in bone marrow failure, leading to a serious shortage of one or more kinds of cells in the blood, or to leukemia. Because this is a relatively new combination of drugs, it is always possible that unanticipated side effects may occur, including death. Many of the drugs used in this treatment program are toxic to the cells in the ovary and testicle and may produce sterility. Recovery of normal fertility is not well studied although we know that some patients treated with this combination have remained fertile after the therapy has been completed. For this reason, men who are about to receive this treatment should, if they wish to have children in the future, consider sperm banking before start of the treatment. These drugs may also be very toxic to an unborn child. Therefore, adequate birth control measures (such as
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 00-C-0133 CONTINUATION: page 9 of 15 pages the contraceptive pill, condoms, diaphragm with contraceptive foam or ointment, contraceptive sponge, etc.) should be used by participants or their sexual partners while receiving treatment on this study. Women of childbearing age will have a pregnancy test, which must be negative at the time of study entry. This test requires that blood be drawn from a vein one or two days prior to the study. The results of the pregnancy test will be made available to you prior to the initiation of the study. Your physicians will watch you closely for side effects and will stop treatment if any side effects become a serious threat to your life or well-being. Your physicians will also stop the treatments if it becomes clear that the treatment is not successfully controlling your disease. Rarely, patients may develop a dangerous side effect from blood transfusions called graft versus host disease (GVH). This disease is caused by white cells from the blood transfusion that can attack your normal tissues and cause death. GVH is preventable by radiating the blood before you receive it. It is important to emphasize that you will not receive any radiation from the blood and the radiation procedure done on the donated blood will not harm you. If you require a blood transfusion at the NIH during this study, you will receive blood that has been radiated. However, if your local physician gives you a blood transfusion, it is important that you make sure the blood has been radiated.
The following general points are indirectly related to your participation in the research study:
1. Unanticipated medical information: During the course of this investigation, it is possible
(although not likely) that we will obtain unanticipated information about your health or genetic background.
2. Release of genetic information:
- Your privacy is very important to us and we will use many safety measures to protect your privacy. However, in spite of all of the safety measures that we will use, we cannot guarantee that your identity will never become known. Although your genetic information is unique to you, you do share some genetic information with your children, parents, brothers, sisters, and other blood relatives. Consequently, it may be possible that genetic information from them could be used to help identify you. Similarly, it may be possible that genetic information from you could be used to help identify them.
- While the controlled-access databases developed for this project will not contain information that is traditionally used to identify you, such as your name, address, telephone number, or social security number, people may develop ways in the future that would allow someone to link your genetic or medical information in our databases back to you. For example, someone could compare information in our databases with information from you (or a blood relative) in another database and be able to identify you (or your blood relative). It also is possible that there could be violations to the security of
STUDY NUMBER: 00-C-0133 CONTINUATION: page 10 of 15 pages the computer systems used to store the codes linking your genetic and medical information to you.
- Since some genetic variations can help to predict the future health problems of you and your relatives, this information might be of interest to health providers, life insurance companies, and others. Patterns of genetic variation also can be used by law enforcement agencies to identify a person or his/her blood relatives. Therefore, your genetic information potentially could be used in ways that could cause you or your family distress, such as by revealing that you (or a blood relative) carry a genetic disease.
- There also may be other privacy risks that we have not foreseen.
Since some genetic variations can help to predict future health problems for you and your relatives, this information might be of interest to health care providers, life insurance companies, and others. However, Federal and State laws provide some protections against discrimination based on genetic information. For example, the Genetic Information Nondiscrimination Act (GINA) makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on your genetic information. However, GINA does not prevent companies that sell life insurance, disability insurance, or long-term care insurance from using genetic information as a reason to deny coverage or set premiums. GINA also does not apply to members of the United States military, individuals covered by the Indian Health Service, or veterans obtaining health care through the Veteran's Administration. Lastly, GINA does not forbid insurance medical underwriting based on your current health status though the Affordable Care Act limits consideration of pre-existing conditions by insurers.
Most patients will have tumor shrinkage with chemotherapy. However, we do not know if the vaccine will be of benefit to you and do not know if you will be cured of your lymphoma. It is also possible that you may not respond to any of this treatment.
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NCT00005780
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Procedures
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Description Of Research Study What Will Happen If You Take Part In This Research Study? Study Design|Epoch-R Treatment|Vaccine Treatment|Research Tests|What Tests Will Be Done On My Samples?
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The study is divided into 3 parts. In the first part, you will undergo a series of tests to determine if you are eligible for the study and to determine the extent (called stage) of your lymphoma. If you are found not to be eligible for the study, you will be referred back to your home physician. If you are eligible, we will ask you to undergo a procedure to obtain lymphoma cells for the vaccine and research tests. A piece of lymphoma tissue to make the vaccine will be removed from places that are safe to biopsy. Alternatively, it may be possible to obtain lymphoma cells from your blood by a procedure called apheresis or bone marrow. These studies and procedures may take up to 4 weeks. In the second part, you will receive a series of treatments with EPOCHR. It usually takes 18 weeks to complete this part of the study. In the third part, you will receive 4 injections of vaccine administered 4 weeks apart, and a 5th injection 8 weeks after the 4th injection. The vaccine treatments will begin around 3 months after you complete EPOCH-R, but in some cases it may be longer, depending on when the vaccine is ready. After the vaccine treatments are completed, you will be followed in our clinic, every few months at first, and then less frequently if the lymphoma does not return. In some circumstances, it is possible you may not receive all or part of the vaccine treatments. In approximately 10% of patients, it is not possible to make a vaccine, or rarely, a patient may have a severe reaction to a vaccine which would make it dangerous to continue. In addition, if a patient's lymphoma begins to grow before the vaccine treatments are completed and they need chemotherapy or radiation that are not part
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 00-C-0133 CONTINUATION: page 3 of 15 pages of this study, the vaccine will not be given. We estimate that around one third of patients will not be able to complete the vaccine treatments for these reasons.
Each chemotherapy treatment period is called a cycle. The cycle is repeated every three weeks and the chemotherapy drugs are administered only during the first five days of every cycle. EPOCH-R consists of prednisone by mouth on days 1 to 5, and etoposide, doxorubicin, and vincristine as an infusion over days 1 to 5 (total of 96 hours), and cyclophosphamide on day 5 by vein. You will receive the infused drugs as an outpatient through a lightweight, portable infusion pump, about the size of a portable tape recorder. The pumps deliver the therapy through an intravenous catheter which is placed in your vein beforehand. You will be taught about the use and care of the pump and what to do if it stops working. The rituximab will be given by vein over several hours on day 1, immediately before the chemotherapy infusion begins, and the cyclophosphamide will be given by intravenous injection over about 15 minutes on day 5, immediately after the chemotherapy infusion is completed. Each cycle lasts 3 weeks: 5 days of chemotherapy followed by 16 days of no chemotherapy. You will receive 6 cycles of EPOCHR. If your lymphoma grows, however, EPOCH-R will be discontinued. Between cycles of treatment, we give another drug, G-CSF, to help your normal bone marrow cells recover from the chemotherapy and produce normal white cells. You will be taught how to inject the G-CSF under your skin (like an insulin shot) each day beginning on day 6 of each cycle and continuing until recovery of the white blood cell count or until day 19 of each cycle. If your white blood cell count is still very low on the day treatment is due to begin again, the chemotherapy may be delayed and the G-CSF restarted until recovery of the white count. Because several of the chemotherapy drugs can lower your resistance to infection, you will receive an antibiotic called Bactrim for three days each week while you are on chemotherapy. If you are allergic to this antibiotic, you will receive the drug, pentamidine, by inhalation once monthly.
At least 3 months is necessary to produce the experimental customized vaccine from your lymphoma cells. It is not always possible to successfully make a vaccine for every patient, so we cannot promise that you will receive a vaccine or that you will have any benefit from the vaccine if you do receive it. The vaccine treatment is given in the clinic and you will be carefully observed. To help the immune system respond to the vaccine, you will also receive daily injections of GM-CSF under the skin, beginning on the day of vaccination and for the three following days. This drug is a naturally occurring protein in our own bodies which has been made into a drug. The vaccine treatments (maximum of 5) will only be given if there are no serious side effects during previous vaccine treatments. It is important that you not take steroid medications or drugs such as aspirin or ibuprofen during the period you are receiving the vaccine without consulting your NIH physicians, unless it is an emergency.
STUDY NUMBER: 00-C-0133 CONTINUATION: page 4 of 15 pages
Research studies will be performed on your blood, bone marrow, tumor tissue or other fluids to look at different genes and proteins that may be involved in the development of your lymphoma or the reaction of the immune system. We will not examine mutations of normal genes from your tissue without obtaining additional permission from you. It may be important to obtain repeat biopsies of tumor tissue after you have enrolled on the study. Repeat biopsies requiring major surgery (e.g., in the chest or the abdomen) will not be performed for research purposes alone but only if absolutely necessary for your medical care. You may decide not to have a biopsy for research purposes and this will not affect your eligibility for this study. Blood samples of approximately 1 teaspoon in size may be drawn up to 5 times on each cycle of EPOCH-R to measure concentrations of chemotherapy drugs. Up to 5 tablespoons of blood may also be drawn during each vaccination to measure the effects of the vaccine. Additionally, a procedure called apheresis will be performed immediately before beginning EPOCH-R chemotherapy and again just before beginning the vaccine treatment to obtain cells for the study of your immune function and possibly for collection of tumor cells for the vaccine. This procedure takes approximately 60 to 90 minutes and is performed in the NIH Department of Transfusion Medicine. In this procedure, your blood will be filtered through a machine to remove the white cells, and your normal blood cells and platelets will be returned to you. The progress of your response will be followed by CT scans of your body and blood tests.
Your blood and tissue that is collected will be used to look for specific changes in the DNA in tumors that could be used to develop new ways of diagnosing and treating cancer. DNA (also called deoxyribonucleic acid) are the molecules inside cells that carry genetic information and pass it from one generation of cells to the next - like an instruction manual. Normal tissue contains the DNA (instructions) that you were born with, DNA in tumor cells has changed - or mutated - and we think that change in the DNA is what causes tumors to form and to grow, forming the cancer genome or DNA. In order to determine which parts of the DNA have mutated, we will compare the DNA in your tumor cells to DNA from your normal cells. When we are examining these pieces of your DNA, it is possible that we could identify possible changes in other parts of your DNA that are not related to this research. These are known as "incidental medical findings". These include:
- Changes in genes that are related to diseases other than cancer - Changes in genes that are not known to cause any disease. These are known as normal variations.
- Changes in genes that are new and of uncertain clinical importance. This means that we do not know if they could cause or contribute to a disease or if they are normal variations.
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 00-C-0133 CONTINUATION: page 5 of 15 pages However, the analyses that we perform in our laboratory are for research purposes only; they are not nearly as sensitive as the tests that are performed in a laboratory that is certified to perform genetic testing. Changes that we observe unrelated to our research may or may not be valid. Therefore, we do not plan to inform you of the results of testing on your tissue and blood that is performed in our research lab. However, in the unlikely event that we discover a finding believed to be clinically important based on medical standards at the time we first analyze your results, we will contact you. This could be many years in the future. We will ask you to have an additional tube of blood drawn to verify the findings we have seen in our lab. If the results are verified, you will be re-contacted and offered (at our expense) to have genetic education and counseling to explain the results. If you do not want to come to NIH, we will help you find a local genetic healthcare provider who can explain it to you (at your expense). You should not assume that if you are not contacted, that you do not have any gene variants that might be related to a disease. Who else besides the investigators on this study will know the results of my sample testing? Once we obtain any of the samples listed above, the investigators take all your personal information off those samples and label them with a study code number. Only the investigators on this study know who the sample came from. The key linking your personal information with the code number is kept in a secure computer data base, with access only to key research staff who will be discussing this study with you. Once the sample has been labeled with a code, it is sent to a variety of NIH laboratories for storage and testing. No one testing your samples will be able to link the results to you personally. Specimens obtained during your participation in this study may be sent for testing to investigators outside of NCI or the NIH. All samples will be coded to protect your privacy and no personal information will be included. Other investigators on this study will have access to limited clinical and biologic data such as age, gender and disease status. Your individual genomic data and health information will be put in a controlled-access database. This means that only researchers who apply for and get permission to use the information for a specific research project will be able to access the information. Your genomic data and health information will not be labeled with your name or other information that could be used to identify you. Researchers approved to access information in the database have agreed not to attempt to identify you. How long will your samples be stored? The samples collected during this study will be stored for as long as the study is open. When this study is closed, we will keep the samples for future research.
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NCT00005780
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Purpose of Research
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Why Is This Study Being Done?|Why Are You Being Asked To Take Part In This Study?
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Mantle cell is a form of cancer of the white blood cells called lymphocytes. In mantle cell, the abnormal lymphocytes multiply and accumulate in lymph nodes and elsewhere. Standard treatment with chemotherapy can often control the mantle cell for a period but in most patients, INSTITUTE: National Cancer Institute STUDY NUMBER: 00-C-0133 CONTINUATION: page 2 of 15 pages the disease does not go entirely away or comes back. In this study, we are testing a vaccine to determine if it can stimulate your own immune system to fight the cancer. Experiments in the laboratory have shown that vaccines of this type work better if there is very little lymphoma present when the vaccine is given. For this reason, we will first treat all patients with EPOCH chemotherapy and rituximab (called EPOCH-R). EPOCH (each letter stands for one of the drugs used in the combination) uses standard chemotherapy drugs and has been shown to have a high degree of effectiveness in lymphomas. Recent evidence indicates that the effects of chemotherapy may be improved by the use of a new drug called Rituximab. Although rituximab is not an experimental drug, its use in this study is considered to be experimental because it is unproven if it will increase the effectiveness of EPOCH therapy. Rituximab is a special kind of drug called an antibody, which binds to a specific molecule (called CD20) present on mantle cell lymphomas. It is important to note that although the drugs in EPOCH-R are standard, we do not know how effective this combination will be in patients with mantle cell lymphoma.
You have been invited to participate in this study because you have mantle cell lymphoma. This is a clinical research study to test a new investigational approach using EPOCH-R chemotherapy and a vaccine directed against your lymphoma cells.
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NCT00006436
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Alternatives
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Alternative Approaches Or Treatments
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Alternative treatments for AIDS-lymphoma include:
Standard combination chemotherapy regimens. These are sometimes given in lower than standard doses along with antiretroviral therapy.
Treatment with single chemotherapy drugs. Therapy with single drugs is better tolerated than combination therapy, and often produce shrinkage of tumor. However, they rarely cure lymphomas.
Radiation (X-ray) treatments. Tumor growth can be stopped in the areas that receive radiation, but it cannot control disease that has spread to multiple areas because the whole body cannot be irradiated without extreme toxicity.
Surgery can successfully remove tumors. However, removal of a tumor by surgery rarely if ever cures lymphoma because the tumors have spread to multiple areas.
Occasionally, patients do not want therapy unless the tumor is causing problems.
However, AIDS-related lymphomas are almost always aggressive and will quickly cause symptoms unless treated. Some patients may feel that chemotherapy is not the best approach for them and may wish to have comfort care only. These are issues that should be discussed with your physicians.
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NCT00006436
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Confidentiality
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Protections Against Misuse Of Genetic Information|Confidentiality Protections Provided In This Study Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality|Privacy Act
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This study involves genetic testing on samples. Some genetic information can help predict future health problems of you and your family and this information might be of interest to your employers or insurers. The Genetic Information Nondiscrimination Act (GINA) is a federal law that prohibits plans and health insurers from requesting genetic information or using genetic information. It also prohibits employment discrimination based on your health information. However, GINA does not address discrimination by companies that sell life insurance, disability insurance, or long-term care insurance. GINA also does not protect you against discrimination based on an already-diagnosed condition or disease that has a genetic component.
We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
The NIH and other government agencies, like the Food and Drug Administration (FDA),
which are involved in keeping research safe for people.
National Institutes of Health Intramural Institutional Review Board
Some of the specimens and/or data obtained may be sent to researchers outside of the National Cancer Institute to perform additional research studies designed to help us better understand lymphoma.
The researchers conducting this study and the NIH follow applicable laws and policies to keep your identifying information private to the extent possible. However, there is always a chance that, despite our best efforts, your identity and/or information about your participation in this research may be inadvertently released or improperly accessed by unauthorized persons. In most cases, the NIH will not release any identifiable information collected about you without your written permission. However, your information may be shared as described in the section of this document on sharing of specimens and data, and as further outlined in the following sections. Further, the information collected for this study is protected by NIH under a Certificate of Confidentiality and the Privacy Act.
To help us protect your privacy, the NIH Intramural Program has received a Certificate of Confidentiality (Certificate). With this certificate, researchers may not release or use data or information about you except in certain circumstances. NIH researchers must not share information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a court. The Certificate does not protect your information when it:
1. is disclosed to people connected with the research, for example, information may be used for auditing or program evaluation internally by the NIH; or 2. is required to be disclosed by Federal, State, or local laws, for example, when information must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA);
3. is for other research;
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4. is disclosed with your consent.
The Certificate does not prevent you from voluntarily releasing information about yourself or your involvement in this research. The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or others including, for example, child abuse and neglect, and by signing below you consent to those disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice and Acknowledgement of Information Practices consent.
The Federal Privacy Act generally protects the confidentiality of your NIH medical records we collect under the authority of the Public Health Service Act. In some cases, the Privacy Act protections differ from the Certificate of Confidentiality. For example, sometimes the Privacy Act allows release of information from your medical record without your permission, for example, if it is requested by Congress. Information may also be released for certain research purposes with due consideration and protection, to those engaged by the agency for research purposes, to certain federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is involved in a lawsuit. However, NIH will only release information from your medical record if it is permitted by both the Certificate of Confidentiality and the Privacy Act.
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NCT00006436
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Duration of Study Involvement
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Before You Begin The Study|During The Study|How Long Will Your Samples Be Stored?|When You Are Finished Taking The Drugs (Treatment)
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Prior to getting any treatment, there are a number of tests that must be completed. As reviewed in the paragraph above, you will undergo a lumbar puncture to remove a small amount of spinal fluid (about 1-2 teaspoons) that will be tested for the presence of lymphoma cells. A lumbar puncture is done by inserting a small sterile needle through the skin and muscle, going between the bones of the spine in the lower back until the needle punctures the spinal canal covering. The spinal fluid will then drain out through the needle on its own. Other tests that you will have done include either a computed tomogram (CAT Scan) of the head, or an MRI of the head. These tests help to see if there are any tumors growing in the brain tissue. CAT scans will also be done of your chest, abdomen, and pelvis. This will help to see if there are any tumors in these parts of your body. Another test to help determine whether lymphoma is present is a positron emission tomography scan (PET scan). This scan is accomplished by injecting a kind of glucose into your blood, and the scanning machine can measure how different cells in the body use it. This can help determine where the lymphoma is, because the lymphoma cells use the glucose differently from other types of cells. Another procedure required is called a bone marrow biopsy. This procedure is done by inserting a small hollow needle through the bone, usually in the back of the pelvis bone, to get some of the bone marrow. The bone marrow is then inspected for evidence of lymphoma. You will also have an Electrocardiogram (ECG) which is a test that is performed while you lie still for about 5 minutes. It involves placing electrodes (small stickers that are attached to wires that go to the machine) on your chest and arms/legs and recording the electrical activity of your heart.
EPOCH-R Chemotherapy The chemotherapy you will receive on this experimental protocol is called EPOCH-R. Each letter in this name stands for the name of a drug that is part of the chemotherapy regimen. The individual drugs will be discussed below. EPOCH-R is different from standard chemotherapy because some drugs are administered over a 4-day period (96-hours) instead of over several hours. Experimental studies in patients with AIDS-lymphoma and in lymphoma without HIV infection suggest that administering some drugs over a 4-day (96 hours) period may increase their effectiveness and reduce toxicity. Although EPOCH-R is a combination of 6 non-experimental drugs, the way the drugs are used is experimental in AIDS-related lymphoma. Rituximab is a monoclonal antibody (a protein that specifically binds to proteins that occur on the surface of lymphoma cells). When rituximab attaches to these cell surface proteins, it may cause the lymphoma cells to die, or make them more sensitive to EPOCH. The Food and Drug Administration has approved rituximab for use in a type of lymphoma that is not HIV-associated. Rituximab is not an experimental drug. The use of rituximab with EPOCH in AIDS is experimental. There is a theoretical possibility that File in Section 4: Protocol Consent (1) Version Date: 03/17/2021 Page 3 of 25 CC pre rCR ICF template v. 12.01.20 EPOCH with rituximab can worsen your immune function, because rituximab decreases the number of B-lymphocytes in your body. B-lymphocytes are important in that they produce antibodies that are important in certain kinds of infections. Therefore, rituximab could make you more prone to bacterial and other infections. The rationale for using the rituximab with EPOCH is to see if there is evidence that combining these therapies is tolerated or not, and to see if it appears to improve the effect of the EPOCH against the lymphoma so that fewer than the standard number of cycles of standard therapy can be administered. The rituximab will be administered twice during each treatment cycle: first immediately before the other drugs are given, and second, at the end of the 96 hours right before the cyclophosphamide is given. It may take several hours to give the rituximab because if it is infused too quickly it can make you feel ill (headache, shortness of breath, rash). You will receive three of the drugs, etoposide, doxorubicin and vincristine, over 4 days (days 1 to 5) through a catheter placed in a large vein. A portable pump that you will carry around with you will infuse the drugs. You do not need to be hospitalized for this therapy but you will have to come to the clinic every day to have the chemotherapy replaced in the pumps. You will also take prednisone by mouth on days 1 through 5, and on day 5, you will receive cyclophosphamide by intravenous injection (the drug will be injected directly into the vein with a needle or catheter) over approximately 30 minutes. The doses of chemotherapy will be adjusted, based on how well you tolerate the therapy. Because chemotherapy damages your bone marrow, you will receive a non-experimental drug called filgrastim (also called granulocyte-colony stimulating factor or GCSF), which helps stimulate bone marrow function. You will receive this for approximately two weeks, beginning on the sixth day of therapy. The nurses will teach you to administer the filgrastim as a daily injection just under the skin (like an insulin shot). You will receive as few as three cycles and a maximum of six cycles of EPOCH-R chemotherapy. Each cycle is repeated every 3 weeks, although a cycle may be delayed for medical reasons. The size of your tumors will be evaluated with computerized tomography (CT) scans, and PET scans before you start treatment. These scans will be repeated after you have completed the 2nd through 6th cycles of EPOCH-R. You will receive one additional cycle of treatment past when it appears that your tumor has completely responded to treatment: therefore, you may receive as few as 3 cycles of chemotherapy.
Treatment will be stopped if the tumor is growing or if you are unable to safely tolerate the therapy.
Supportive Therapy Because chemotherapy can lower your resistance to infection, you will receive preventative therapy for a kind of pneumonia called Pneumocystis carinii with a drug called trimethoprim/sulfamethoxazole (Bactrim®). This is administered three times a week during the time you receive EPOCH and rituximab. If you are allergic to Bactrim or cannot tolerate it, you may receive an alternative therapy. If you need prophylaxis or treatment for other AIDS-related infections such as fungal infections (like thrush), mycobacterium avium complex (MAC), tuberculosis (TB), toxoplasmosis, cryptosporidium, or cytomegalovirus, those medications may have to be stopped during the EPOCH infusions to avoid potentially harmful drug interactions. While you are being treated with EPOCH, the intent is that your anti-HIV drugs will be continued. These drugs may inhibit your bone marrow function or interact with the chemotherapy to cause
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other or increased side effects. However, it has been shown that continuing anti-retroviral drugs may be important for your overall treatment. Samples for Research Blood samples will be collected for research studies to look at the response of HIV and the cancer to the treatment. These will be collected prior to and after each cycle of treatment (up to 4 tablespoons each time), and after treatment at about 2 months, every 3 months for 1 year, and every 6 months for an additional year (up to 4 tablespoons each time). In addition, portions of tissue collected as part of other, routine procedures that you may have had in the past or in the future for your disease will also be collected for research studies. Optional Blood Collection for Research You may be asked to donate a small amount of blood for research. If you agree to this, you will have up to 7 tablespoons of blood collected up to 4 times after you complete treatment. The blood collected is exclusively for research purposes and will not benefit you. It might help other people in the future. The decision to participate in this part of the research is optional, and no matter what you decide to do, it will not affect your care. If you agree to the optional blood samples, your agreement will be documented in the records.
The samples collected during this study will be stored for as long as the study is open. When this study is closed, we will keep the samples for future research.
If your disease does not enter remission or it recurs, you may need further therapy. If no protocols are available for the treatment of your disease, you will be returned to the care of your local physician. It is important to stress that participation in this protocol does not constitute a promise of long-term medical care at the Clinical Center.
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NCT00006436
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Participant Responsibilities
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Reimbursement Will You Receive Reimbursement Or Direct Payment By Nih As Part Of Your Participation?
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On this study, the NCI will reimburse the cost for some of your expenses such as those for hotel, travel, meals. Some of these costs may be paid directly by the NIH and some may be reimbursed after you have paid. The amount and form of these payments are determined by the NCI Travel and Lodging Reimbursement Policy. You will be given a summary of the policy which provides more information. If your travel to the NIH Clinical Center (e.g. flight, hotel) is arranged and paid for by the NIH, the agency making the reservations and their representatives will have access to your identifiable information.
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NCT00006436
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Possible Risks, Discomforts, and Inconveniences
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Birth Control|Risks Or Discomforts Of Participation What Side Effects Or Risks Can I Expect From Being In This Study?|Occasional, Some May Be Serious In 100 People Receiving Doxorubicin, From 4 To 20 May Have:|Cyclophosphamide: Common, Some May Be Serious|Prednisone: Common, Some May Be Serious|Dexamethasone: Common, Some May Be Serious|Vincristine: Common, Some May Be Serious|Etoposide: Common, Some May Be Serious|Rituximab (Rituxan): Common, Some May Be Serious|File In Section 4: Protocol Consent (1) Version Date: 03/17/2021 Page 14 Of 25 Cc Pre Rcr Icf Template V. 12.01.20 Rare, And Serious|Filgrastim: Common, Some May Be Serious|Other Risks|Risks Associated With The Study Procedures:|What Are The Risks Of Radiation From Being In This Study?|Other Risks:|Psychological Or Social Risks Associated With Loss Of Privacy|2. Release Of Genetic Information:|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?
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Because it is possible that drugs in EPOCH-R can affect a developing fetus, and because you can transmit HIV to your sexual partner, you will be asked to practice an effective method of barrier birth control and safe sex while you are participating in this study. Effective forms of birth control include:
- abstinence intrauterine device (IUD)
- hormonal [birth control pills, injections, or implants] - tubal ligation - vasectomy Because of the danger of HIV infection with the exchange of body fluids, all participants in this study must agree to safe sex practices and to use condoms while engaging in sexual intercourse.
Your physicians will watch you closely for these side effects and will stop treatment if any side effects become a serious threat to your life or wellbeing. Your physicians will also stop the treatments if it becomes clear that the treatment is not successfully controlling your disease. There are unforeseeable risks whenever investigational treatment programs are undertaken, including death. Chemotherapy has the potential of causing a rapid acceleration of HIV disease and increasing the chances of developing opportunistic infections with viruses, parasites or fungi. Your doctors will monitor you carefully for these complications. If they should become a threat to your health and it is considered dangerous to proceed with the investigational treatment protocol, you will be removed from the study. If you have complications of therapy, you will be evaluated and appropriately treated for any acute effects of treatment. In the event of emergency medical needs, referral to the closest facility is mandatory, and NIH cannot reimburse for those costs. Risks and side effects related to the treatment and the procedures on this study are identified below:
Heart failure or heart attack which may cause shortness of breath, swelling of ankles, cough or tiredness which may occur years after the dose Abnormal heartbeat Cancer of the bone marrow (leukemia) caused by chemotherapy Damage to the lungs which may cause shortness of breath when combined with radiation Infection, especially when white blood cell count is low Bruising, bleeding Anemia which may cause tiredness, or may require transfusion Hepatitis or damage to the liver which may cause yellowing of eyes and skin, swelling Kidney damage which may require dialysis Sores in the mouth or throat Belly pain Nausea, diarrhea Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat Damage to the skin which may cause pain Swelling and redness at the site of the medication injection or area of previous radiation Loss of nails Darkening of the nail beds or skin or hands and feet
In 100 people receiving Doxorubicin, 3 or fewer may have:
Severe blood infection
In 100 people receiving Cyclophosphamide, more than 20 and up to 100 may have:
Hair loss, skin changes, rash, change in nails Nausea, vomiting, diarrhea, loss of appetite, pain in belly Sores in mouth Infection, especially when white blood cell count is low Absence of menstrual period which may decrease the ability to have children Blood in urine
In 100 people receiving Cyclophosphamide, from 4 to 20 may have:
Damage to the bone marrow (irreversible) which may cause infection, bleeding, may require transfusions Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat Loss or absence of sperm which may lead to an inability to father children Stuffy nose Scarring of the lungs which may cause shortness of breath Fluid around the heart
In 100 people receiving Cyclophosphamide, 3 or fewer may have:
Severe skin rash with blisters and peeling which can involve mouth and other parts of the body Damage to the heart or heart failure which may cause shortness of breath, swelling of ankles, cough or tiredness A new cancer including cancer of bone marrow (leukemia) caused by chemotherapy Swelling of the body including the brain which may cause dizziness, confusion
In 100 people receiving Prednisone, more than 20 and up to 100 may have:
High blood pressure which may cause headaches, dizziness, blurred vision Pain in belly Loss of bone tissue Mood swings In children and adolescents: decreased height Swelling of the body, tiredness, bruising Increased appetite and weight gain in the belly, face, back and shoulders Difficulty sleeping Skin changes, acne
In 100 people receiving Prednisone, from 4 to 20 may have:
Blood clot which may cause swelling, pain, shortness of breath Infection Kidney stones Diabetes Glaucoma Cloudiness of the eye, visual disturbances, blurred vision A tear or a hole in the bowels which may cause belly pain or that may require surgery Heartburn Damage to the bone which may cause joint pain and loss of motion Numbness and tingling of the arms, legs and upper body Muscle weakness Non-healing wound
In 100 people receiving Prednisone, 3 or fewer may have:
Bleeding from sores in the stomach Broken bones
In 100 people receiving Dexamethasone, more than 20 and up to 100 may have:
High blood pressure which may cause headaches, dizziness Pain in belly Infection Diabetes Loss of bone tissue Damage to the bone which may cause joint pain or loss of motion Mood swings In children and adolescents: decreased height Swelling of the body, tiredness, bruising Increased appetite and weight gain in belly, face, back and shoulders Difficulty sleeping Skin changes, rash, acne
In 100 people receiving Vincristine, more than 20 and up to 100 may have:
Constipation, nausea, vomiting Hair loss Pain or redness at the site of injection Numbness and tingling of fingers or toes Headache, jaw pain and/or muscle pain Weakness and difficulty walking Swelling of lower legs
In 100 people receiving Vincristine, from 4 to 20 may have:
Swelling that may be accompanied by confusion, and dizziness Paralysis, weakness, headache, confusion Hoarseness Drooping eyelids Visual loss Difficulty with balance and hearing File in Section 4: Protocol Consent (1) Version Date: 03/17/2021 Page 12 of 25 CC pre rCR ICF template v. 12.01.20 RARE, AND SERIOUS
In 100 people receiving Vincristine, 3 or fewer may have:
Seizure
In 100 people receiving Etoposide, more than 20 and up to 100 may have:
Infection, especially when white blood cell count is low Anemia which may require transfusion Bruising, bleeding Sores in mouth which may cause difficulty swallowing Diarrhea, loss of appetite, nausea, vomiting Tiredness Fever Chills Hair loss
In 100 people receiving Etoposide, from 4 to 20 may have:
Heart failure or heart attack which may cause chest pain, shortness of breath, swelling of ankles, and tiredness Liver damage which may cause yellowing of eyes and skin, swelling Severe skin rash with blisters and peeling which can involve inside of mouth and other parts of the body
In 100 people receiving Etoposide, 3 or fewer may have:
Cancer of bone marrow caused by chemotherapy Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat
In 100 people receiving Rituximab, more than 20 and up to 100 may have:
Nausea Chills, fever Reaction during or following infusion of the drug Infection, especially when white blood cell count is low Anemia which may require blood transfusions Numbness and tingling of the arms and legs Tiredness
In 100 people receiving Rituximab, from 4 to 20 may have:
Bruising, bleeding Abnormal heartbeat Heart attack or heart failure which may cause shortness of breath, swelling of ankles, and tiredness Sores in eye A tear or a hole in the bowels that may require surgery Diarrhea, vomiting Pain Swelling of the body Hepatitis, or liver damage which may cause yellow eyes and skin Dizziness, headache Kidney damage which may require dialysis Cough Scarring of the lungs Stuffy nose Blockage of internal organs which may cause shortness of breath, wheezing, vomiting Increased sweating Itching, rash, blisters on the skin Severe skin rash with blisters and peeling which can involve mouth and other parts of the body Low blood pressure which may cause feeling faint
In 100 people receiving Rituximab, 3 or fewer may have:
Damage to the brain caused by a virus which may result in tiredness, weakness, changes in thinking, and disability. This is called progressive multifocal leukoencephalopathy (PML).
Heart stops beating
In 100 people receiving Filgrastim, more than 20 and up to 100 may have:
Nose bleed Anemia which may require transfusion Pain Diarrhea Fever Tiredness Hair loss
In 100 people receiving Filgrastim, from 4 to 20 may have:
Fluid in the organs which may cause low blood pressure, shortness of breath, swelling of ankles Damage to the lungs which may cause shortness of breath Internal bleeding which may cause coughing up blood Cough Swelling or tenderness of vessels Headache
In 100 people receiving Filgrastim, 3 or fewer may have:
Rupture of the spleen causing sudden or severe pain in the left side of abdomen spreading up to your shoulder
There is also the possible side effect of significant nerve damage, that may result in weakness in the extremities, including in one or both legs (also called "peripheral motor neuropathy"). This is a rare, but possible risk of intrathecal therapy, including with cytarabine and methotrexate, and has been seen on this study.
It is important to emphasize that when you have a decreased white blood cell count following chemotherapy, you are at high risk of developing an infection. Such infections may be very serious and cause death if not quickly and properly treated. Therefore, if you have a temperature greater than 38.3°C (101°F), you must call your doctor immediately.
Chemotherapy may also cause your platelets to fall; since platelets are the blood elements that permit blood to clot, this may place you at increased risk of serious bleeding. It may be necessary to give you transfusions of platelets if your platelet counts reach very low levels.
There is a small chance that damage to the normal bone marrow may eventually result in bone marrow failure, leading to a serious shortage of one or more kinds of cells in the blood, leukemia and death.
Many of the drugs used in this treatment program are toxic to the egg cells in the ovary and sperm cells in the testicle and may produce sterility. Recovery of normal fertility, although theoretically possible, is very uncertain.
To determine if this research study is suitable for you, a number of tests need to be done. This period of evaluation may take up to two weeks and if possible will be done on an outpatient basis. These may include blood and urine tests, Computerized tomography (CT) or magnetic resonance imaging (MRI) scans, radioisotope scans, glucose uptake scans, ECG and biopsies of tumor tissue and bone marrow, and a spinal tap (removal of a small amount spinal fluid from the spinal canal by inserting a needle into the lower back). Over the course of this study, approximately one pint of blood will be taken.
The risks associated with bone marrow biopsies include local pain, bleeding, and infection.
The risks associated with a spinal tap also include pain, bleeding, and local infection.
Under very rare circumstances, brain damage can occur, causing death. This only occurs if there is a large brain mass or tumor causing pressure, and for this reason, we will obtain a brain scan if there is any suspicion that you have a brain tumor.
The risks of radiation related to FDG and CT scans are described below. In addition to those radiation risks, CT scans that employ contrast may cause allergic reactions, injection site reactions abdominal discomfort and fainting. MRIs carry no radiation risks but are contraindicated in participants with metal in their bodies. In patients that receive gadolinium contrast with MRIs, allergic reactions, injection site reactions and kidney damage may occur.
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The risk related to blood sampling include pain and bruising, lightheadedness, and rarely, fainting.
It is important to obtain fresh biopsies of tumor tissue, even if you already had a biopsy before coming to the NIH. This is done to both confirm the diagnosis and for research purposes. If you have a biopsy done, we will collect portions of it for the research study as it will help us understand why AIDS-related lymphomas are difficult to treat. Biopsies requiring major surgery (e.g. in the chest or the abdomen) will not be performed for research purposes alone but only if necessary for your medical care. Risks of biopsies include pain, bleeding, infection, and the risks to the particular area undergoing surgery. General anesthesia itself is generally safe but has a very small risk of major complications such as heart attack or stroke. The risks of general anesthesia will be explained to you in more detail at the time of surgery if it is needed. Blood samples, other body fluids and tissues that are obtained during testing, operative procedures, or other standard medical practices will also be used for research purposes. In order to receive EPOCH-R, you will need to have a catheter placed in a large vein. This catheter can be placed in the arm, neck, chest or groin areas. In general, the chest, neck or arm is preferred. For most people, the safest catheters are placed temporarily and removed after each chemotherapy treatment. For some patients, semi-permanent catheters are preferable. These catheters stay in place until all cycles of therapy are completed. While they may seem more convenient, they are associated with a more frequent occurrence of complications. The risks associated with insertion of catheters include pain, bleeding, infection, and puncture of the lung. A lung puncture can result in lung collapse, which might require insertion of a tube into the chest cavity (usually for a day or two) to help the lung reinflate. The long-term risks of catheters include infection and clotting of the vein, and this is more common with semi-permanent catheters. If side effects occur, it may be necessary to remove the catheter, and to treat the infection and/or clot with medication. These risks will be explained to you in more detail at the time of the catheter insertion. You will be advised witch catheter type is likely to be best for you. The catheter type that is best for you may change over the course of therapy.
During your participation in this research study, you may be exposed to radiation from CTs of the Chest, Abdomen and Pelvis and PET scans each year. The amount of radiation exposure from these procedures is equal to approximately 17.1 rem. A rem is a unit of absorbed radiation. Every day, people are exposed to low levels of radiation that come from the sun and the environment around them. The average person in the United States receives a radiation exposure of 0.3 rem per year from these sources. This type of radiation is called "background radiation." This study will expose you to more radiation than you get from everyday background radiation. No one knows for sure whether exposure to these low amounts of radiation is harmful to your body. The CT and PET scans that you get in this study will expose you to roughly the same amount of radiation as 57 years' worth of background radiation. Being exposed to too much radiation can cause harmful side effects such as an increase in the risk of cancer. The risk depends on how much radiation you are exposed to. Please be aware that about 40 out of 100 people (40%) will get cancer during their lifetime, and 20 out of 100 (20%) will die from cancer. The risk of getting cancer from
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the radiation exposure in this study is 1.7 out of 100 (1.7%) and of getting a fatal cancer is 0.9 out of 100 (0.9%) You may not participate in this study if you are pregnant. If you are able to become pregnant, we will perform a pregnancy test before exposing you to radiation. You must tell us if you may have become pregnant within the previous 14 days because the pregnancy test is unreliable during that time.
As a patient-volunteer, you may experience considerable psychological stress. This study requires a substantial time commitment over a 2-year period with requirements for blood tests, x-ray's, drug administration, and physician appointments. There is also uncertainty regarding the ultimate outcome of your treatment. Some patients will feel worse, for at least some period during the investigational treatment period, than they did before treatment. Patient-volunteers are encouraged to discuss their feelings with staff members. Your treating physicians, in concert with other members of the treatment team, wish to identify any problems that are affecting your emotional wellbeing, and to help you deal with them. Should you experience sad or disturbing feelings, we have counselors available, and you should notify a member of the treatment team so that arrangements can be made for counseling if you wish it.
The following general points are indirectly related to your participation in the research study:
1. Unanticipated medical information: During the course of this investigation, it is possible
(although not likely) that we will obtain unanticipated information about your health or genetic background.
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Your privacy is very important to us and we will use many safety measures to protect your privacy. However, in spite of all of the safety measures that we will use, we cannot guarantee that your identity will never become known. Although your genetic information is unique to you, you do share some genetic information with your children, parents, brothers, sisters, and other blood relatives. Consequently, it may be possible that genetic information from them could be used to help identify you. Similarly, it may be possible that genetic information from you could be used to help identify them.
While the controlled-access databases developed for this project will not contain information that is traditionally used to identify you, such as your name, address, telephone number, or social security number, people may develop ways in the future that would allow someone to link your genetic or medical information in our databases back to you. For example, someone could compare information in our databases with information from you (or a blood relative) in another database and be able to identify you (or your blood relative). It also is possible that there could be violations to the security of the computer systems used to store the codes linking your genetic and medical information to you.
Since some genetic variations can help to predict the future health problems of you and your relatives, this information might be of interest to health providers, life insurance companies, and others. Patterns of genetic variation also can be used by law enforcement agencies to identify a person or his/her blood relatives. Therefore, your genetic information potentially could be used in ways that could cause you or your family distress, such as by revealing that you (or a blood relative) carry a genetic disease.
There also may be other privacy risks that we have not foreseen.
As a result of participating in this investigational treatment program, you will receive evaluation and treatment of your lymphoma and AIDS. All of the medications, tests, hospitalizations and physician services at the NIH will be free of charge to you. As information is gathered from this trial, results will be shared with you (of course information regarding other patients will never
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include the patients name or any other identifying information, to insure patient confidentiality). Although the EPOCH-R chemotherapy is experimental, all of the drugs in EPOCH-R except the rituximab are contained in standard treatment regimens for HIV-related lymphomas. Moreover, we have tested EPOCH alone in AIDS-lymphoma, and it appears to be safe and effective. However, we cannot be certain if you will be cured of your lymphoma and it is possible your tumor may be resistant to chemotherapy, and if this occurs, you may not receive any benefit from this treatment.
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NCT00006436
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Procedures
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What Will Happen If You Take Part In This Research Study?|What Tests Will Be Done On My Samples?|Drugs Used In The Spinal Fluid For Lymphoma:
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None of the drugs in this treatment are experimental. The United States Food and Drug Administration has approved all of the drugs for use in lymphoma. However, as explained below, the way the drugs in this research protocol are given in combination together is experimental. In addition to receiving chemotherapy into your veins, you will also receive chemotherapy directly into your spinal fluid using a procedure called lumbar puncture (explained in the next paragraph). This part of the therapy is not experimental. The spinal fluid bathes the brain and spinal cord and is separated from the rest of your body fluids by tissue that prevents the chemotherapy drugs given by vein from getting into the spinal fluid. It is important to get the chemotherapy into the spinal fluid because in AIDS-lymphoma, the spinal fluid and brain frequently get lymphoma in them. The chemotherapy must therefore be given by lumbar puncture or some other method to get it directly into the spinal fluid. We will test to see whether there is any evidence of lymphoma in your brain or spinal fluid before deciding how to treat the spinal fluid. If there is no evidence that the lymphoma has gotten into your brain or spinal fluid, you will receive the chemotherapy into the spinal fluid twice weekly every third week for 6 doses. If there is evidence of brain or spinal fluid lymphoma, then you will receive up to 3 drugs simultaneously into the spinal fluid. These treatments will be given twice weekly for at least 4 weeks, and will continue for once weekly for at least 4 more weeks, and then once monthly for at least 6 more treatments. Sometimes it is necessary to have the neurosurgeons perform an operation to place a device called an Ommaya into your head that the chemotherapy is given through if the lumbar punctures are not feasible. If you need an Ommaya, you will be consented separately for that. Additionally, you may require radiation therapy to your head and spine. As stated above, this part of the therapy is not experimental, and will be determined on the basis of your individual medical needs. Even though this part of the therapy is not experimental, it is required as part of the research protocol.
Your blood and tissue that is collected will be used to look for specific changes in the DNA in tumors that could be used to develop new ways of diagnosing and treating cancer, and to understand more about HIV. DNA (also called deoxyribonucleic acid) are the molecules inside cells that carry genetic information and pass it from one generation of cells to the next - like an instruction manual. Normal tissue contains the DNA (instructions) that you were born with, DNA in tumor cells has changed - or mutated - and we think that change in the DNA is what causes tumors to form and to grow, forming the cancer genome or DNA. In order to determine which parts of the DNA have mutated, we will compare the DNA in your tumor cells to DNA from your normal cells. When we are examining these pieces of your DNA, it is possible that we could identify possible changes in other parts of your DNA that are not related to this research. These are known as "incidental medical findings". These include:
Changes in genes that are related to diseases other than cancer
Changes in genes that are not known to cause any disease. These are known as normal variations.
Changes in genes that are new and of uncertain clinical importance. This means that we do not know if they could cause or contribute to a disease or if they are normal variations.
However, the analyses that we perform in our laboratory are for research purposes only; they are not nearly as sensitive as the tests that are performed in a laboratory that is certified to perform genetic testing. Changes that we observe unrelated to our research may or may not be valid. Therefore, we do not plan to inform you of the results of testing on your tissue and blood that is performed in our research lab. However, in the unlikely event that we discover a finding believed to be clinically important based on medical standards at the time we first analyze your results, we will contact you. This could be many years in the future. We will ask you to have an additional
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tube of blood drawn to verify the findings we have seen in our lab. If the results are verified, you will be re-contacted and offered the opportunity to come to NIH to have genetic education and counseling to explain this result; at the time of any such event(s), these activities will be paid for by the NCI. If you do not want to come to NIH a referral to a genetic healthcare provider will be provided to discuss the results (at your expense). Who else besides the investigators on this study will know the results of my sample testing? Once we obtain any of the samples listed above, the investigators take all your personal information off those samples and label them with a study code number. Only the investigators on this study know who the sample came from. The key linking your personal information with the code number is kept in a secure computer data base, with access only to key research staff who will be discussing this study with you. Once the sample has been labeled with a code, it is sent to a variety of NIH laboratories for storage and testing. No one testing your samples will be able to link the results to you personally. Specimens obtained during your participation in this study may be sent for testing to investigators outside of NCI or the NIH. All samples will be coded to protect your privacy and no personal information will be included. Other investigators on this study will have access to limited clinical and biologic data such as age, gender and disease status.
Methotrexate, when administered into the spinal fluid, may cause low blood counts and ulcerations in the mouth, stomach, and intestines. It can cause acute headache, back pain, stiff neck, and /or fever; it can also cause weakness or paralysis of certain muscles. It can cause seizures and coma. Other side effects it can cause are usually associated with intravenous administration rather than intrathecal (lumbar puncture administration), but these include liver function abnormalities, inflammation and scarring of the lungs, inflammation of the tissue covering the heart, and severe skin reactions. This drug can rarely cause damage to the lungs.
Leucovorin is related to the vitamin folic acid. For the most part, it is nontoxic in therapeutic doses. However, severe allergic reactions have been reported, but these are rare. It is used to decrease the side effects of the methotrexate.
Cytosine Arabinoside given my lumber puncture can cause nausea, vomiting, fever, and headaches. Rarely, it can cause weakness and seizures. When given into the spinal fluid, it does not usually cause systemic toxicity, but we will monitor you for low blood counts, and liver function abnormalities, which can occur with cytosine arabinoside when given by vein.
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NCT00006436
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Purpose of Research
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Why Is This Study Being Done?|Why Are You Being Asked To Take Part In This Study?|Description Of Research Study
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The major purpose of this research study is to determine if the experimental combination of chemotherapy drugs given to you through your veins can lead to disappearance of lymphoma (by our best ability to test for it) within as few cycles as possible, and to see if the lymphoma will
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continue to stay undetectable for at least one year if the treatment is stopped one cycle after you enter remission.
You have a cancer called non-Hodgkin's lymphoma (NHL) and you are also infected with the human immunodeficiency virus (HIV). In patients like yourself, the lymphoma often grows and spreads rapidly so chemotherapy is usually used for treatment. Chemotherapy will be discussed in more detail later in this document.
The HIV infection has damaged your immune system, and chemotherapy probably causes further damage to your immune system. If it were possible to limit the amount of immune damage due to chemotherapy, this might decrease the number of infections and decrease the risk of developing cancer in the future. This research protocol is designed to help answer whether it may be possible to limit the amount of damage chemotherapy causes to the immune system by reducing the total amount of chemotherapy given. However, if too little chemotherapy is given, then the cancer will not be cured. In this research protocol, we will administer a combination of drugs for lymphoma and perform sensitive tests to see if all evidence of your cancer goes away very early in the course of your treatment. If the cancer goes away quickly, then the treatment will be stopped after 9 weeks of therapy. If your cancer continues to be evident, you will receive up to 18 weeks of treatment. The standard treatment for your type of cancer is usually given for 18 to 24 weeks. We will also monitor your immune system to see how much immune damage occurs with the treatment. After you finish treatment, we will monitor your immune system to see if it improves or not, and we will look for evidence of the cancer coming back.
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NCT00006436
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Voluntary Participation
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It Is Your Choice To Take Part In The Study
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You may choose not to take part in this study for any reason. If you join this study, you may change your mind and stop participating in the study at any time and for any reason. In either case, you will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you must be taking part in a study or are being considered for a study. If you do choose to leave the study, please inform your study team to ensure a safe withdrawal from the research.
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NCT00006436
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Withdrawal from Study
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Stopping Therapy
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Your doctor may decide to take you off this study for the following reasons:
- if he/she believes that it is in your best interest
- if your disease comes back during treatment - if you have side effects from the treatment that are your doctor thinks are too severe
- if new information shows that another treatment would be better for you - if you do not follow the study requirements (for instance, if you are not coming for your study visits when scheduled).
In this case, you will be informed of the reason therapy is being stopped. You can stop taking part in the study at any time. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your regular doctor first. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines,
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information collected on you up until that point may still be provided to designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases **cannot** be recalled and destroyed.
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NCT00026793
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Alternatives
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Alternative Approaches Or Treatments
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The imaging techniques have no therapeutic role. These techniques are being studied to try and determine if they may be useful in assessing Kaposi's sarcoma lesions using non-invasive methods. Patients can elect to not have any imaging performed without jeopardizing their participation in other protocols in the NIH Clinical Center.
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NCT00026793
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Confidentiality
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Will Your Medical Information Be Kept Private?
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We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
- The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.
- National Cancer Institute Institutional Review Board
When we report the results of this research study, we may include photographs and images taken during the course of the study. We will not mention you by name and we will take care so that you will not be recognizable (i.e. no identifiable images of your face will be shown).
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NCT00026793
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Duration of Study Involvement
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During The Study
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During your participation in this protocol, these experimental imaging techniques will be performed when you begin the study as a baseline evaluation, and then once about every 3 months while you are on the study in order to compare the results of the tests over time. Also, if your Kaposi's sarcoma should improve or worsen, or you change therapy for your KS, the imaging techniques may be repeated in an effort to correlate the findings of the imaging with the clinical changes observed in your KS. In general, we will try to schedule the examinations on this protocol to take place on the same days you are being seen in the clinic for other purposes.
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NCT00026793
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Participant's Rights
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Research Subject'S Rights What Are The Costs Of Taking Part In This Study?
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If you choose to take part in the study, the following will apply, in keeping with the NIH policy:
- You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
Participation in this protocol is voluntary you may discontinue your participation in this investigational protocol at any time. You will be given a copy of the consent for your records. There are no penalties imposed on you for withdrawing your participation in the protocol. You may ask questions of the staff, and indeed you are encouraged to do so. Any significant new findings that relate to your treatment will be discussed with you. It is important to stress that participation in this protocol does not constitute a promise of long-term medical care here at the NIH Clinical Center. If there is no research study suitable for you and your state of disease, you will be returned to the care of your private doctor.
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 01-C-0158 CONTINUATION: page 5 of 8 pages
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NCT00026793
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Possible Risks, Discomforts, and Inconveniences
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Risks Or Discomforts Of Participation What Side Effects Or Risks Can I Expect From Being In This Study?|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?
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The risks of participating in this study are minimal. There are no invasive procedures involved other than the drawing of a small amount of blood from your vein through a needle, which will be done by standard procedures. The imaging techniques use a variety of methods as described
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 01-C-0158 CONTINUATION: page 4 of 8 pages above to estimate the vascularity in the lesions and blood flow in the lesions. The techniques will require your time, which may be inconvenient to you. The time will vary according to how many lesions are studied by the techniques. If you find that the amount of time you have to spend having the lesions assessed is too great, we will minimize the number of lesions studies by the techniques, if possible.
There are no direct benefits to you of participation in the study. The study is an attempt to develop new methods for assessing Kaposi's sarcoma skin lesions using non-invasive methods.
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NCT00026793
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Procedures
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What Will Happen If You Take Part In This Research Study?
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On this protocol, you will have conventional photographs made of your lesions, and four additional experimental methods performed. The four methods are called:
1) laser Doppler imaging 2) multi-spectral imaging 3) infrared thermal imaging, and 4) optical coherence tomography.
In addition, comparisons will be made with normal skin surrounding the lesions or on the opposite side of your body. Laser Doppler imaging takes about 3 minutes to perform on each lesion. It uses a low power laser beam that scans across the skin lesion being measured. The instrument does not touch your skin. You may be asked to have a blood pressure cuff put on your arm and have laser Doppler imaging performed before and after the cuff is inflated for a short time (generally less than thirty seconds).We do not believe that this instrument will harm your skin: in standard practice a similar machine is used to measure how deeply severe burns affect the skin. If you stare at a laser light it could harm your eyes, but precautions will be taken so that you will not stare at it. It is also used to assess allergic responses in the skin. However, its use in Kaposi's sarcoma is experimental. The purpose of this experimental use is to attempt to measure the amount of blood flow through the blood vessels in the Kaposi's sarcoma lesions. It will not have a therapeutic effect on the lesions. The multi-spectral imaging exam should take about 2 minutes to perform on each lesion. It uses principles of the way hemoglobin absorbs light. Hemoglobin is a protein in the blood that carries oxygen to your tissues. The light on the multi-spectral imaging instrument is absorbed differently depending on whether the hemoglobin has oxygen attached to it or not. This will allow an estimate to be made regarding the total blood STUDY NUMBER: 01-C-0158 CONTINUATION: page 3 of 8 pages volume, and how much of it is carrying oxygen or not. We do not believe that the instrument will harm you. The technique will not make your Kaposi's sarcoma improve. The thermal imaging takes about a minute to perform on each lesion. It uses a special camera to take digital infrared pictures of your skin. This enables us to form a picture of the temperature of your KS lesions and thus assess the blood flow in the Kaposi's sarcoma lesions. We do not believe that the camera and lights will harm you. The spectral domain optical coherence tomography (OCT) exam should take less than 2 minutes per lesion. This technique allows a three dimensional image to be made of the lesion structure. The principle of OCT is based on interference of two light beams, one illuminating and reflecting from the sample and the second one reflecting from a mirror. The light source used is of low power and non-invasive. The system will be placed approximately 4cm away from your skin, and nothing should contact your skin directly. The structural information obtained by this technique will be correlated to the vascular information obtained with the other techniques and will help to further evaluate treatment outcome. We do not believe that the instrument will harm you. We anticipate that the whole exam (involving the four tests) will generally take an hour or less to perform. You may also be asked to have a small amount of blood (less than a tablespoon) drawn from your vein for a complete blood count the days you have the lesion assessments performed. You may occasionally be asked to have two examinations performed the same day if your schedule permits. We do not expect that any of these tests will make your HIV infection or Kaposi's sarcoma improve or become more severe.
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NCT00026793
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Purpose of Research
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Why Is This Study Being Done?
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This is a research study to develop noninvasive methods of determining the density of blood vessels and the amount of blood flow in skin that is affected by Kaposi's sarcoma. The intent is to develop techniques that may in the future help us better assess the clinical state of Kaposi's sarcoma lesions. Why are you being asked to take part in this study? You are being asked to take part in this study because you have Kaposi's Sarcoma.
STUDY NUMBER: 01-C-0158 CONTINUATION: page 2 of 8 pages
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NCT00026793
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Voluntary Participation
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Optional Studies|Yes No Initials_________
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We would like to keep some of the imaging studies and data that are collected for future research. These imaging studies and data will be identified by a number and not your name. The use of your imaging studies and data will be for research purposes only and will not benefit you. It is also possible that the stored imaging studies and data may never be used. Results of research done on your imaging studies and data will not be available to you or your doctor. It might help people who have cancer and other diseases in the future. If you decide now that your imaging studies and data can be kept for research, you can change your mind at any time. Just contact us and let us know that you do not want us to use your specimens and/or data. Then any specimens that remain will be destroyed and your data will not be used for future research. Please read each sentence below and think about your choice. After reading each sentence, circle and initial the answer that is right for you. No matter what you decide to do, it will not affect your care.
1. My imaging studies and data may be kept for use in research to learn about, prevent, or treat cancer. Yes No Initials_________
2. My imaging studies and data may be kept for use in research to learn about, prevent or treat other health problems (for example: diabetes, Alzheimer's disease, or heart disease).
3. Someone may contact me in the future to ask permission to use my imaging studies and/or data in new research not included in this consent. Yes No Initials_________
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent
STUDY NUMBER: 01-C-0158 CONTINUATION: page 7 of 8 pages
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NCT00026793
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Withdrawal from Study
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Stopping Participation
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Your doctor may decide to stop your participation in this study
- if he/she believes that it is in your best interest
- if you do not follow the study requirements
In this case, you will be informed of the reason that your participation is being stopped. You can stop taking part in the study at any time. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your regular doctor first. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be used by the researchers. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases cannot be recalled and destroyed.
Any decisions regarding therapy of your Kaposi's sarcoma will be made by your treating physician using regular clinical information (including counts and measurements of lesions). The results of the non-invasive imaging will not be used to alter your clinical care, as at present these are research tools only. If you are enrolled on a research treatment study for Kaposi's sarcoma, the decisions about your treatment will be made by your treating physician in accordance with the requirements of that study.
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NCT00038727
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Alternatives
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Alternative Treatments For **Impaired Glucose** Tolerance
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The DPP showed that metformin or the DPP intensive lifestyle program is effective in preventing or delaying the development of diabetes. At the end of DPP all participants were offered the DPP lifestyle training in group sessions. During DPPOS, continued lifestyle lessons were offered to all participants on a quarterly basis. During Phase 3 of DPPOS these sessions will be offered once annually. If you wish to participate in an additional lifestyle modification program outside the study, you are free to do so. Although the DPP proved its effectiveness, metformin is currently not an approved drug for prevention of diabetes. If you are not in the metformin treatment group and you want to take metformin, you should discuss this with your primary healthcare provider.
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NCT00038727
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Confidentiality
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Confidentiality
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To help us further protect your privacy, the investigators have obtained a Confidentiality Certificate from the Department of Health and Human Services (DHHS).
With this Certificate, the investigators cannot be forced (for example by court subpoena) to disclose research information that may identify you in any Federal, State, or local civil, criminal, administrative, legislative, or other proceedings. Disclosure will be necessary, however, upon request of DHHS for audit or program evaluation purposes.
You should understand that a Confidentiality Certificate does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this research. Note however, that if an insurer or employer learns about your participation, and obtains your consent to receive research information, then the investigator may not use the Certificate of Confidentiality to withhold this information. This means that you and your family must also actively protect your own privacy.
Finally, you should understand that the investigator is not prevented from taking steps, including reporting to authorities, to prevent serious harm to yourself or others.
Information that we receive from you will be kept confidential to the extent allowed by law. Information we collect about you will be put into a research record that will be sent to a central data site at The George Washington University for statistical analysis, and samples will be sent to a central laboratory at the University of Washington. Your central research record and samples will not be directly identified with your name. A code number and/or letters will identify your records. The link between the code and your name is stored in a secure location at the (insert your institution name.) Only authorized personnel at (insert institution name) will have access to the key to the code. Anonymous coded information may be released to a DPP investigator (or other investigator authorized by the DPP) only after determination of the scientific usefulness of a proposed study. [Insert appropriate language as determined by your IRB].
A description of this clinical trial is available on http://www.Clinical Trials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.
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NCT00038727
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Duration of Study Involvement
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Mid-Year Visit:|Annual Visit:|Interim Visit (Approximately 30 Minutes To 2.5 Hours):|Retinal Photographs And Ocular Tomography (1-2 Hours):
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- At mid-year visits, no measurements will be taken. Mid-year visits will be completed by phone, or occasionally in clinic. You will be asked to answer questions about your health. For those taking study metformin, pills will be provided in person or mailed if the mid-year visit is completed by phone.
For annual visits (approximately 1-4 hours), you will be asked not to eat or drink anything, except water, for 12 hours before your appointment. 1. An electrocardiogram (ECG) will be performed every other year. This will take about one-half hour.
2. Blood pressure will be measured in your arm. This will take about 10 minutes.
3. Body measurements: Your weight will be measured yearly and waist size will be measured every other year. This will take about 10 minutes. You may have your height measured. This will take about 5 minutes.
4. You will receive a test for neuropathy (problems with nerves in the feet). This will involve an examination of the sensation in your feet. This test will take about 5 minutes.
5. Oral glucose tolerance test every other year: This test will take about 2 and ½
hours. A blood sample will be taken from your arm. You will then be asked to drink a glassful of flavored sugar water over 5 minutes. Another blood sample will be taken from your arm again at 120 minutes. The total amount of blood drawn for this test is approximately 1 tablespoon. All participants will have a fasting blood glucose drawn at each annual visit. A repeat blood draw or an oral glucose tolerance test may be necessary.
6. People with diabetes will not be asked to complete the oral glucose test, but will have a fasting blood glucose drawn (approximately one teaspoon) following the same 12 hour fasting instructions as stated above.
7. Additional blood samples may be taken from your arm at the same time that you are having blood drawn for the oral glucose test or fasting sample, for lipids (blood fats), hemoglobin A1c (HbA1c, a measure of the average blood glucose level control over three months time), serum creatinine (a measure of kidney function), and other blood tests related to diabetes and heart disease (total amount of blood drawn equals approximately 4 to 5 tablespoons). Some of this blood will be stored for future studies described below if you agree. If you were assigned to the metformin group and are taking metformin provided by the study, an additional sample might be drawn for a vitamin B12 test (about 10ml or two teaspoons). A repeat blood sample might be necessary for some persons.
8. You will be asked to provide a urine sample for measurement of urine albumin and creatinine (measures of kidney function). A repeat urine sample may be necessary for some persons.
9. You may be asked to complete several questionnaires. You may be asked questions about your health, medications, physical activity, diet and feelings. Some of the questionnaires will be completed by interview and others you will complete yourself. These will take about 30 minutes to 2 hours to complete.
10. You may be given questionnaires regarding your cognitive status such as memory and verbal learning .
11. Your physical function may be measured by grip strength, balance, chair rises, and walking speed.
12. You may be asked to walk for 6 minutes down a corridor at a normal pace. The distance you walk and how fast you walk will be measured.
13. Your lung function may be measured using a portable spirometer. . A
spirometer is a hand-held device that you blow intoas hard and as fast as you can. You will be asked to do this several times. A new, clean mouthpiece will be used for each participant. Spirometry takes about 20 minutes.
14. If you are a woman assigned to and taking metformin provided by the DPPOS
and there is a chance that you could become pregnant, you will be asked whether you are willing to use medically effective birth control methods for the duration of the study. If you decide to become pregnant during the study, you must notify the clinic staff immediately. If there is a chance that you could be pregnant, a pregnancy test will be done. If you suspect that you are pregnant you should stop your metformin immediately and notify clinic staff.
15. We have previously asked you to give us personal information such as address, phone numbers, and social security number, to help us to reach you if we lose touch. We will ask you to update this information each year and as necessary.
16. Some people enrolled in DPPOS have developed serious illness or disability that prevent them from participating in study data collection on their own. You will be asked to name a health informant (proxy) to DPPOS in the event you cannot participate in study data collection on your own. If you choose not to name a health informant (proxy) you may still participate in DPPOS to the extent that you are able.
17. Some people enrolled in DPPOS have moved far away or have physical limitations that may prevent them from visiting their DPPOS clinic. If you cannot have specimens collected at a DPPOS clinic and DPPOS staff cannot come to you for a home visit, we may arrange to have a health technician visit you at home to collect annual blood and urine sample and measures your weight and blood pressure. The DPPOS will provide the health technician with your name, address and/or location of home, phone number and DPPOS study number. This will allow the health technician to schedule the sample collection with you at your convenience. Your samples will be sent to the DPPOS laboratory identified only by your study number but not your name. Your measurements will be given to your DPPOS clinic staff. Your contact information will be destroyed by the health technician after the data collection. You will receive clear instructions from your clinic about what to expect and how to get the tests completed, if needed. These tests are completed at no cost to you. If you are taking study metformin and cannot have specimens collected at a DPPOS Clinic, DPPOS needs to check your kidney function once a year and vitamin B12 every other year with a blood test to be sure it is safe for you to continue taking study metformin. If you cannot come to a DPPOS clinic for this blood test, DPPOS may arrange for you to have the blood tests done as described above. If you agree, DPPOS may also contact your doctor to check if you had this safety test in the last year. If the kidney blood test cannot be done once a year, we will ask you to stop taking study metformin.
Some participants may be asked at times to attend an interim visit. At this visit the following tests/procedures may occur: 1. You may be asked to attend an interim visit for a repeat urine sample, repeat blood sample or oral glucose tolerance test when necessary as indicated above. If you are taking metformin, an additional blood test (1 teaspoon) for kidney function, or if female a pregnancy test, may be required.
2. You may have your weight measured. 3. You may have your blood pressure measured. 4. You may be asked questions concerning your health, given information about your health and health education, or provided with information about the study.
Diabetes diagnosed during study: We ask that you report any symptoms of diabetes to the clinic for further evaluation. Symptoms of diabetes include:
Extreme thirst Frequent urination Blurry vision Unusual tiredness or drowsiness Unexplained weight loss Frequent or recurring skin, gum or bladder infections If you develop diabetes during the study, you will no longer be asked to have the oral glucose tolerance test; however, you will continue to be asked to provide blood for a fasting glucose and hemoglobin A1c test, as well as the other blood samples and tests listed above. In addition, you will be given a general overview of diabetes care. You will be referred to your primary care provider (PCP) for additional diabetes education and follow-up. If you do not have a PCP, we can help you find one. The DPPOS cannot provide individual diabetes counseling and it will be your responsibility to follow-up with your physician for your diabetes care. If you wish, the DPPOS may assist you in locating diabetes care.
If your hemoglobin A1c test reaches 7% or higher and you are taking metformin provided by DPPOS, we will refer you to your physician for evaluation and further treatment, and will no longer provide metformin.
Retinal photos including ocular tomography will be completed during the middle of DPPOS Phase 3. At this visit the following tests/procedures may occur: 1. You will make one visit to a retinal photograph center [local address if available] which will last about one (1) to two (2) hours.
2. You will answer some questions about your eyes, including any allergies to eye drops used to open (dilate) the pupil .These drops are [XXX - replace with clinic-specific language]. A brief examination of your eye will be done to see if this will be safe for you. [Replace with clinic-specific language if necessary] This will not be a complete eye examination by an eye specialist (Ophthalmologist) but only for safety and research purposes.
3. Drops will be put in both eyes to dilate your pupils, and you will wait about 30 minutes for the drops to work.
4. You will have pictures taken with a camera of the back or your eyes (retina)
using a bright flash. There will be about 20 pictures taken of each eye.
5. Another test to examine the back of your eye is the Ocular Tomography test.
This test provides a detailed image of the retina (back of your eye). It is painless and requires about 10 additional minutes.
6. The photographs will be sent to the Reading Center in Wisconsin identified only with a study number. Your name will not be sent.
7. You may be asked to return for additional photos if the first ones were not of acceptable quality for grading, or for other reasons.
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NCT00038727
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Participant's Rights
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Participant'S Statement:
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The study described above has been explained to me. I understand that I
am consenting to participate in the DPPOS. If I have any questions, I know that I can contact one of the investigators listed on the first page.
In addition, I agree to the following: I give permission for my blood and urine to be stored in a central bank
(currently at the University of Washington) for future use by the DPPOS investigators in studies of diabetes, related complications, and heart disease:
______YES ______NO ______INITIALS When I die, the specimens I have donated may still be used for the research purposes agreed to above.
______YES ______NO (my specimens MUST be destroyed once you have been notified of my death).
______INITIALS We are also asking you to allow samples of your blood and your research data to be sent to the NIDDK Central Repositories, a research resource supported by the National Institutes of Health. The Repository collects, stores, and distributes biological samples and associated data from people with many kinds of disorders, from unaffected family members, and from other healthy people. The purpose of this collection is to make samples available for use in research for the study of diabetes, related complications and heart disease after the current study is completed. Sending samples to the Repository may give scientists valuable research material that can help them to develop new diagnostic tests, new treatments, and new ways to prevent diseases.
The Repository will take measures to protect your privacy, although no guarantee of confidentiality can be absolute. Before the DPPOS researchers send samples to the Repository, each sample will be given a code number. Your name and all personal identifying information, such as address, social security number, date of birth, and clinic location will not be included. Therefore, the Repository will not be able to give out your name, or other information that identifies you to the scientists who receive the samples. However, the Repository and scientists will also have some research data about you, such as age, sex, diagnosis, treatment group, race, and outcomes of the study.
You will not receive any direct benefit or payment for participating, but your sample may benefit the future health of the community at large or some particular group. Because other researchers will not have access to your identity, neither you nor your physician will get the eventual results of studies that might be performed using your sample. It is possible that data resulting from use of your sample may eventually be used in a research publication. In that event, your name or other identifying information will not be included, as this information will not be available to the researchers.
It is important for you to understand that there is a small chance that some research may yield results that may indirectly have a negative impact on insurability, employability, and/or family relationships of some individuals or groups of people.
Sometimes, research results in findings or inventions that have value if they are made or sold. These findings or inventions may be patented or licensed, which could give a company the sole right to make and sell products or offer testing based on the discovery. Some of the profits from this may be paid back to the researchers and the organizations doing this study, but you will not receive any financial benefits.
Your donation is voluntary, and if you choose not to participate there will be no penalty or loss of benefits to which you are entitled.
If you agree to have your sample stored in the Repository, you can change your mind up until the end of the DPPOS. When we receive written instructions from you, we will destroy your sample and all information that identifies you. After the DPPOS ends, you will not be able to withdraw your samples because the Repository will not know which one is yours. The samples will stay in the Repository indefinitely or until they are used up.
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NCT00038727
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Possible Risks, Discomforts, and Inconveniences
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Risks, Stress, And Discomfort
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Oral Glucose Tolerance and Blood Tests: The risks of drawing blood include temporary discomfort from the needle stick, possible bruising or redness of the skin, lightheadedness, and on rare occasion, infection. It is possible that some may get nausea or an upset stomach with the glucose (sugar) drink that is given during the oral glucose test. Rarely some people may experience a mild low blood sugar reaction (symptoms like nervousness or sweating) at the end of the test. You will be given a snack to guard against this.
Electrocardiogram (ECG): The risks associated with the use of the ECG
electrodes include possible skin irritation, redness and/or chaffing at the application site.
Metformin: The risks of taking metformin were described to you previously in the DPP and have not changed. This medicine has been used for many years to treat patients with diabetes. Side effects include: loss of appetite, upset stomach, vomiting, stomach pain, diarrhea, bloating or gas, or a funny taste (like metal). These are usually mild and lessen with continued use of the medicine. Mild side effects might happen in one out of five persons. Only one or two persons out of fifty are expected to have to stop metformin because of side effects. Anemia (insufficient Vitamin B12) might also happen very rarely in some persons. Very few persons (3 in 100,000 and usually persons with poor kidney function or with severe liver disease) have serious problems (a condition known as lactic acidosis) with metformin that might result in death. Lactic acidosis has also occurred in people who are heavy or binge alcohol drinkers. Persons with poor kidney function or severe liver disease, women planning to become pregnant, or persons who are heavy or binge alcohol drinkers should not take metformin. You cannot take the study medication, metformin, if you have poor kidney function or severe liver disease or you plan to become pregnant. For those assigned to and taking metformin provided by the DPPOS, tests will be done to check on kidney function and vitamin B12 levels. It is always possible that you could have an unexpected serious reaction to metformin or any other medicine.
Persons with congestive heart failure (CHF) should not take metformin.
You should report the symptoms of CHF, shortness of breath or swelling in the ankles, to your healthcare provider immediately, and stop taking metformin until you are instructed to use it again.
If you are a woman assigned to the Metformin group and taking metformin provided by the DPPOS and there is a chance that you could become pregnant, you will be asked whether you are willing to use medically effective birth control methods for the duration of the study. If you decide to become pregnant during the study, you must notify the clinic staff immediately. If there is a chance that you are pregnant, you should stop the metformin, inform us, and a pregnancy test will be done.
Metformin has not been approved for use in pregnancy. Metformin has not resulted in any increased risk during pregnancy. Some medicines might, however, cause birth defects to an unborn baby. It is important that you tell us if you suspect at all that you might be pregnant. Study medicines will be stopped if you get pregnant. You will continue in the DPPOS if you are pregnant, and will be asked to re-start your study medicine after pregnancy and breast feeding.
There are some other circumstances for which metformin should be discontinued temporarily. These include overnight hospitalization, some surgical procedures and tests using a contrast dye. It is requested that you notify the clinic if any of these situations occur so that you may be instructed concerning stopping the study metformin.
Physical function: You may experience some imbalance or lightheadedness when the walking tests, chair rises, and the balance tests are performed. You may also experience some muscle strain or muscle soreness while the grip strength or other measurements are being performed. There is a rare risk of injury, muscle fatigue, and joint discomfort with some of the tests. This risk is lowered by not doing the test if you have had any new symptoms of heart disease, recent injury, soreness, or any joint procedure in the past 3 months. After the demonstration by the staff, if you feel that any of the motor movements, such as walking, hand gripping a measuring device, rising up from a chair several times, or any of these movements maybe unsafe, do not attempt them. There is a risk that you may find the walking test tiring or too hard to finish. Trained personnel will be there to monitor you to see how you are doing during these tests. You may stop the test if you need to rest. You may also stop to rest if you become tired because of the number of tests.
Lung function **(spirometry):** You may become short of breath, start coughing or experience chest tightness or dizziness while doing the spirometry. You will be asked some questions prior to the spirometry to assure that it is safe for you to do the test.
Eye drops: Some people feel slight burning or tearing when the eye drops are put in. Your vision may be blurred while the eyes are dilated, and you should not drive for 2-3 hours after the test. There is a less than 1% chance that the drops could cause closed-angle glaucoma, a rapid increase in the pressure inside the eye. Symptoms could include pain in your eye, decreased vision, headache and/or nausea. If any of these symptoms occur after your visit, you should call the eye center immediately [phone number] and follow their instructions.
Photographs: There is no risk to your eyes from the photos. Some people feel discomfort from the flash; however, this lasts only a few seconds.
This eye photography study is for research purposes only and should not replace regular eye examinations and follow-up. [As with any investigational study, there may be adverse events or side effects that are currently unknown and it is possible that certain of these unknown risks could be permanent, serious or life threatening. insert only if required by local IRB]
Other: Some people may feel uncomfortable about some of the questions we ask. You may decide not to answer any question.
There is also the risk that a breach of confidentiality could occur, however, every effort is made to prevent this from happening.
As with any investigational study, there may be adverse events or side effects that are currently unknown and it is possible that certain of these unknown risks could be permanent, serious or life threatening.
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NCT00038727
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Procedures
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Procedures
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If you choose to take part in Phase 3 of the DPPOS you will continue in your original randomly assigned intervention group. Although many of the features of DPPOS Phase 3 are the same as for DPPOS, there are some differences: - Participants in all treatment groups will be invited to take part in an annual Healthy Lifestyle Program (HELP) class. HELP sessions will focus on diabetes- related topics. The original exercise and diet goals of the intensive lifestyle intervention, walking (or similar activity) 2 ½ hours (150 minutes) per week and using healthy eating habits to lose and maintain a 7% weight loss, may be discussed. You may be weighed. A trained professional will lead the group sessions. Each class will last about 1 hour. If you choose not to attend the HELP classes, you may still take part in the DPPOS.
- For participants in the original metformin intervention group: you may be asked to continue taking metformin depending on your laboratory tests or medical conditions. If you are unable or choose not to take metformin, you may still take part in the DPPOS.
- For participants in the original intensive lifestyle intervention group: healthy lifestyle messages will be reinforced at the annual visit as part of your "lifestyle check-up".
Clinic Visits: As a participant in the DPPOS, you will be asked to attend a clinic visit once or twice a year. In some cases, you may be asked to attend an additional interim visit. If you are not able to come to the clinic, the clinical center staff may offer to visit you for data collection. If neither a clinic nor home visit is possible, you may be asked to provide information by telephone. These visits and procedures to be completed are described below:
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NCT00038727
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Purpose of Research
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Investigator'S Statement: Purpose And Background
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This research study is called the Diabetes Prevention Program Outcomes Study and is an extension of the Diabetes Prevention Program (DPP), of which you were a participant. The purpose of Phase 3 of the DPPOS is to look at the effects of the study interventions on the development of type 2 diabetes as well as diabetes related health problems and cancer diagnosis over a longer period of time (up to five additional years). In this type of research, health information is combined from many volunteers.
Diabetes is a disease in which there is too much glucose (sugar) in the blood. Diabetes causes damage to blood vessels, heart, kidneys, eyes, and nerves.
Diabetes affects at least 24 million Americans. Ninety to ninety-five percent of those affected have type 2 diabetes.
The interventions that were studied during the DPP were intensive lifestyle modification and metformin. The results of the DPP showed that the risk of type 2 diabetes was reduced by 58% in the intensive lifestyle group and 31% in the metformin group. The DPPOS is examining the continued effects of these study interventions over a longer period of time. You will take part in the DPPOS for up to five additional years. All participants who were in the original DPP study groups randomized to intensive lifestyle modification, metformin or placebo (approximately 3,200) are being asked to continue to take part in the DPPOS.
DPPOS is currently funded through January 2021. This document obtains your consent to continue in DPPOS through January 2021 (Phase 3).
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NCT00051311
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Possible Risks, Discomforts, and Inconveniences
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Risks Or Discomforts Of Participation|Potential Benefits Of Participation
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Filgrastim (G-CSF) may cause bone and muscle pain, headache, fever and chills, tiredness, and difficulty sleeping. There can be some pain, bruising and swelling at the injection site. Some people who receive filgrastim shots and apheresis have a temporary decrease in blood platelets (cells that help your blood to clot); however, this side effect has not led to an increased amount of bleeding. To be safe, your platelet count will be checked during and after the apheresis procedure. Rare side effects of filgrastim include allergic reactions with rash, itching, difficulty breathing, chest pain, and a lowering of the blood pressure. These reactions resolve once filgrastim has been stopped. Very rarely, filgrastim has been reported to cause swelling and rupture of the spleen, usually requiring surgery to remove the spleen, and resulting in some deaths. Filgrastim should not be used in patients with a history of having a heart attack, stroke, severe rheumatoid arthritis, or other serious autoimmune diseases. If you think that you may have any of these conditions, and you have not discussed them with your physician or any of the other NCI staff, be sure to notify them about these medical problems immediately. Side effects of blood being drawn include pain and bruising in the area where the needle was placed, lightheadedness, or rarely, fainting. When too much blood is taken, one's red blood cell count may drop causing anemia. However, the amount of blood that you will donate in this study (a total of 20 teaspoons) should not cause anemia. To be safe, we will check your red blood cell level. If we find that you have anemia, we will give you treatment for this condition (in the form of iron tablets). The apheresis procedure may cause low blood pressure. Other side effects include tingling in the mouth, fingers and toes, and mild muscle cramps; these side effects are due to the anticoagulant (blood thinner) used to prevent your blood from clotting while it passes through the apheresis machine. Adjusting or stopping the apheresis machine or administering calcium can correct these problems. Possible side effects of a temporary IV in the femoral vein of your groin (if required) include bleeding, bruising, blood clot, or pain where the IV was placed. Only physicians with experience in this procedure will place a femoral IV catheter. They will discuss the risks with you before the procedure.
By participating in this investigational transplant protocol, you will provide a source of stem cells and immune cells for your relative. However, there are no direct benefits to your health from participating in this study. Hopefully, your donation of cells will help to improve your relative's cancer. Your participation may also help increase our knowledge of stem cell transplants and improve the way that we treat cancer.
NIH 2514-2, Minor Patient's Assent to Participate In A Clinical Research Study STUDY NUMBER: 03-C-0077 CONTINUATION: page 5 of 6 pages Research Subject's Rights Participation in this research study is voluntary. You may stop your participation in the study at any time. There are no penalties for withdrawing from the study. You will be given a copy of the consent for your records. We encourage you to ask our staff any questions that you have.
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NCT00051311
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Procedures
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Your Evaluation For Stem Cell Donation|The Donation
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On your first visit to the NIH Clinical Center, you will have a complete medical history and physical examination in the NCI Medical Oncology Clinical Research Unit clinic. You will meet with members of the transplant team, who will review your medical history and explain the procedure for stem cell donation. About 5 to 10 teaspoons of blood will be drawn to check how closely you and your relative are genetically matched; you must match on all 6 of 6 genetic markers to enroll in the study. This blood sample will also be used to check the health of your kidneys and liver. We will also test for exposure to a variety of infections, including hepatitis B and C, human immunodeficiency virus (HIV, the virus that causes acquired immunodeficiency syndrome, or AIDS), syphilis, and a virus called cytomegalovirus (CMV). You will also be tested for the viruses for hepatitis A, HTLV-1 and -2, adenovirus, Epstein-Barr virus, herpes simplex virus, and a parasite called Toxoplasma. Staff from the NIH Department of Transfusion Medicine will also examine your arms to see if your veins are suitable for the apheresis procedure. To donate cells, you must be in good health without evidence of any active or chronic infection. You must not have a medical history of stroke, myocardial infarction (heart attack), severe heart disease, or autoimmune disease such as rheumatoid arthritis. If you have symptoms of heart disease, you cannot be a donor. If you have had any heart operations such as a bypass graft or angioplasty, a cardiologist must evaluate you and state that you are not putting yourself at risk by donating cells. Your blood will be tested for diseases that are spread through the blood. These diseases include HIV (the virus that causes AIDS) and hepatitis B and C. If you have a positive test for any of these diseases, we will inform you, and you will not be allowed to be a donor. If you are a woman, you will need to take a urine pregnancy test. Because of health risks to the fetus, pregnant women cannot be donors. Breastfeeding women can be donors only if they are willing and able to stop breast feeding while receiving filgrastim injections and having stem cells collected. Women can resume breast feeding after the stem cell collection is finished.
Once it is decided that you can be a donor, we will schedule the procedure for stem cell collection. In order to collect your stem cells, we will give you injections (with needles) of a drug called filgrastim, also called "G-CSF" and "Neupogen". Filgrastim is a growth factor that our bodies normally produce in small amounts; it works like a hormone to stimulate the growth of our white blood cells, and it causes stem cells to be released from the bone marrow into the
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NCT00051311
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Purpose of Research
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Description Of Research Study
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We are conducting a study of allogeneic stem cell transplantation for cancers (and certain pre-cancerous conditions) of the blood and immune system. In the past, stem cell transplantation was more commonly called "bone marrow transplantation." When "stem cells" for the blood and immune system are taken from one person (called the "donor") and given to another person (called the "recipient"), it is known as "allogeneic" stem cell transplantation. Stem cells are immature blood cells, like seeds; they can grow in the bone marrow and produce all of the cells needed for normal blood and immunity. Originally, stem cells were collected for transplantation by taking samples of bone marrow from the donor. Now, though, most allogeneic transplants are performed with stem cells collected from the donor's blood; this is often called "peripheral blood stem cell transplantation."
PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL
RESEARCH STUDY
- Adult Patient or - Parent, for Minor Patient NIH-2514-1 (4-97) P.A.: 09-25-0099 File in Section 4: Protocol Consent (2)
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NCT00051311
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Voluntary Participation
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Nih 2514-2, Minor Patient'S Assent To Participate In A Clinical Research Study|Nih 2514-2, Minor Patient'S Assent To Participate In A Clinical Research Study|Nih 2514-2, Minor Patient'S Assent To Participate In A Clinical Research Study|Nih 2514-2, Minor Patient'S Assent To Participate In A Clinical Research Study
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STUDY NUMBER: 03-C-0077 CONTINUATION: page 2 of 6 pages Allogeneic stem cell transplantation (SCT) has been used successfully to treat, and sometimes cure, many kinds of cancer or pre-cancerous conditions that originate in the blood or immune system cells. Chemotherapy drugs and/or radiation are used to eliminate most of the cancerous or abnormal cells from the recipient's system, along with many of his or her own stem cells and immune cells. Donor stem cells can then replace the recipient's stem cells in the bone marrow, restoring normal blood production and immunity; this process is called "engraftment". In this way, the recipient of an allogeneic SCT receives not just new blood cells but an entire new immune system. Immune cells from the donor are important not only to protect the transplant recipient from infections; these transplanted cells can also attack and eliminate the abnormal cells that caused the patient's disease. This type of immune attack is called the "graft-versus-tumor" (GVT) effect, and it is thought to be the main reason that allogeneic SCT can sometimes cure patients of these conditions.
Your relative has a disease for which allogeneic SCT may be an effective treatment. That is why we are inviting you to donate stem cells for transplantation into your relative. If accepted by your relative's body, your stem cells will help his or her body to grow normal blood and immune cells.
STUDY NUMBER: 03-C-0077 CONTINUATION: page 3 of 6 pages blood. We use a highly purified filgrastim product that is produced in laboratories by genetically engineered bacteria.
The U.S. Food and Drug Administration and the National Marrow Donor Program have both approved filgrastim for use in stem cell collection. Four days before the scheduled stem cell collection, you will begin to receive filgrastim injections under the skin of your arm or thigh. We will teach you or a family member how to give these injections at home. They will be given for a period of 5, 6, or 7 days. Usually, you will be ready for stem cell collection on the fifth day of filgrastim injections. A blood test, requiring only a small amount of blood (two teaspoons), will help us decide that. Once the stem cells are in your blood, they can be collected from your veins using a process called "apheresis."
Apheresis is a standard procedure performed by trained personnel in the NIH Department of Transfusion Medicine. During apheresis, an intravenous catheter (IV) is placed into a vein in each of your arms. Your blood will circulate from one arm into a machine that collects and saves your white blood cells and stem cells. The rest of your blood will go back into your body through the other arm. The collection usually takes 4 to 6 hours, after which the stem cells are frozen and stored until the day of the transplant. The IV's will be removed after the cells are collected. If your arm veins are not large enough for apheresis, an experienced physician will temporarily insert a special IV into the femoral vein (in your groin) for the procedure. This IV would be removed after your stem cells are collected. If you require a femoral IV catheter for apheresis and more than one stem cell collection is needed (see below), you will be admitted to the NIH Clinical Center overnight for care of the catheter until the collection is completed (usually the next day). Apheresis avoids the need for an operation under anesthesia to take stem cells directly from the bone marrow in your hip bones. We usually gather enough stem cells in a single collection to be able to perform a transplant to your relative. Sometimes it is necessary to continue the filgrastim shots and repeat the apheresis on the next day (day 6). Rarely, a third apheresis on day 7 could be required. If we still did not have enough cells to perform the transplant, we would ask that you rest for two weeks before repeating the filgrastim shots and apheresis. Within one week after the apheresis procedure(s), you will be checked for any side effects at the Outpatient NCI Clinic. In rare cases, we are unable to collect enough stem cells to perform a transplant. If this occurs, you will be removed from the study; your relative will also be removed from the study before transplantation unless he or she has another suitable donor.
Sometimes we ask donors to donate additional cells. The additional cells can be used to help the transplant take over full production of blood and immune cells in your relative. These cells can also be used to "boost" your relative's new immune system and can sometimes enhance the graft-versus-tumor effect. Immune cells called "lymphocytes" are most commonly used in these situations. Donor lymphocytes are usually collected by apheresis without treating the donor with filgrastim before the cells are collected. However, in some situations you may be asked to undergo a course of filgrastim before lymphocyte collection.
STUDY NUMBER: 03-C-0077 CONTINUATION: page 4 of 6 pages Alternative Approaches or Treatments Usually, enough of your stem cells can be collected by apheresis. Most donors prefer this method of collecting stem cells to having an operation on their hipbone to collect bone marrow cells. Also, stem cell collection by apheresis avoids the risks of general anesthesia ("putting you under") that come with an operation.
STUDY NUMBER: 03-C-0077 CONTINUATION: page 2 of 6 pages Allogeneic stem cell transplantation (SCT) has been used successfully to treat, and sometimes cure, many kinds of cancer or pre-cancerous conditions that originate in the blood or immune system cells. Chemotherapy drugs and/or radiation are used to eliminate most of the cancerous or abnormal cells from the recipient's system, along with many of his or her own stem cells and immune cells. Donor stem cells can then replace the recipient's stem cells in the bone marrow, restoring normal blood production and immunity; this process is called "engraftment". In this way, the recipient of an allogeneic SCT receives not just new blood cells but an entire new immune system. Immune cells from the donor are important not only to protect the transplant recipient from infections; these transplanted cells can also attack and eliminate the abnormal cells that caused the patient's disease. This type of immune attack is called the "graft-versus-tumor" (GVT) effect, and it is thought to be the main reason that allogeneic SCT can sometimes cure patients of these conditions.
Your relative has a disease for which allogeneic SCT may be an effective treatment. That is why we are inviting you to donate stem cells for transplantation into your relative. If accepted by your relative's body, your stem cells will help his or her body to grow normal blood and immune cells.
STUDY NUMBER: 03-C-0077 CONTINUATION: page 3 of 6 pages blood. We use a highly purified filgrastim product that is produced in laboratories by genetically engineered bacteria.
The U.S. Food and Drug Administration and the National Marrow Donor Program have both approved filgrastim for use in stem cell collection. Four days before the scheduled stem cell collection, you will begin to receive filgrastim injections under the skin of your arm or thigh. We will teach you or a family member how to give these injections at home. They will be given for a period of 5, 6, or 7 days. Usually, you will be ready for stem cell collection on the fifth day of filgrastim injections. A blood test, requiring only a small amount of blood (two teaspoons), will help us decide that. Once the stem cells are in your blood, they can be collected from your veins using a process called "apheresis."
Apheresis is a standard procedure performed by trained personnel in the NIH Department of Transfusion Medicine. During apheresis, an intravenous catheter (IV) is placed into a vein in each of your arms. Your blood will circulate from one arm into a machine that collects and saves your white blood cells and stem cells. The rest of your blood will go back into your body through the other arm. The collection usually takes 4 to 6 hours, after which the stem cells are frozen and stored until the day of the transplant. The IV's will be removed after the cells are collected. If your arm veins are not large enough for apheresis, an experienced physician will temporarily insert a special IV into the femoral vein (in your groin) for the procedure. This IV would be removed after your stem cells are collected. If you require a femoral IV catheter for apheresis and more than one stem cell collection is needed (see below), you will be admitted to the NIH Clinical Center overnight for care of the catheter until the collection is completed (usually the next day). Apheresis avoids the need for an operation under anesthesia to take stem cells directly from the bone marrow in your hip bones. We usually gather enough stem cells in a single collection to be able to perform a transplant to your relative. Sometimes it is necessary to continue the filgrastim shots and repeat the apheresis on the next day (day 6). Rarely, a third apheresis on day 7 could be required. If we still did not have enough cells to perform the transplant, we would ask that you rest for two weeks before repeating the filgrastim shots and apheresis. Within one week after the apheresis procedure(s), you will be checked for any side effects at the Outpatient NCI Clinic. In rare cases, we are unable to collect enough stem cells to perform a transplant. If this occurs, you will be removed from the study; your relative will also be removed from the study before transplantation unless he or she has another suitable donor.
Sometimes we ask donors to donate additional cells. The additional cells can be used to help the transplant take over full production of blood and immune cells in your relative. These cells can also be used to "boost" your relative's new immune system and can sometimes enhance the graft-versus-tumor effect. Immune cells called "lymphocytes" are most commonly used in these situations. Donor lymphocytes are usually collected by apheresis without treating the donor with filgrastim before the cells are collected. However, in some situations you may be asked to undergo a course of filgrastim before lymphocyte collection.
STUDY NUMBER: 03-C-0077 CONTINUATION: page 4 of 6 pages Alternative Approaches or Treatments Usually, enough of your stem cells can be collected by apheresis. Most donors prefer this method of collecting stem cells to having an operation on their hipbone to collect bone marrow cells. Also, stem cell collection by apheresis avoids the risks of general anesthesia ("putting you under") that come with an operation.
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NCT00069238
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Alternatives
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Alternative Approaches Or Treatments
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It should be emphasized that we do not know at this point whether the combination of drugs we propose to give you/your child is superior, inferior, or equivalent to standard combination chemotherapy for your/your child's disease. Alternative procedures that could be used to treat your/your child's disease include:
1. Other combination drug regimens and other schedules of the same drugs used in this study. For example, a chemotherapy called CHOP given in the conventional manner would be suitable standard therapy for your/your child's condition.
2. Treatment with single drugs. This is known to produce brief responses of a few months' duration in many patients but to have little beneficial effect in long-term control of the disease.
3. Radiation (X-ray) treatments. This can stop tumor growth in particular locations, such as bone, abdomen, and other sites but is not successful in controlling the disease overall unless the disease is very localized at the start of therapy.
4. Surgery. As with radiation, surgery can be successful in removing tumor from particular locations but cannot be used successfully to remove all lymphoma cells from the body, since the disease is almost always present in multiple locations. Also, surgery cannot be used against tumor in some of the organs most commonly involved by lymphoma, such as the liver or the lungs.
5. Waiting, without active therapy. Although a period of watchful waiting is appropriate treatment for some kinds of tumors, in lymphomas similar to yours/your child's, the disease will often grow and spread rapidly if no treatment is administered.
6. No treatment. You/your child can choose not to receive any therapy for your/your child's lymphoma. In this case, your/your child's doctor can give you/your child's medications that will make you/your child feel comfortable.
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NCT00069238
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Confidentiality
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Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality
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We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
x The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.
x National Cancer Institute Institutional Review Board
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most the Web site will include a summary of the results. You can search this Web site at any time.
To help us protect your privacy, we have obtained a Certificate of Confidentiality. The researchers can use this Certificate to legally refuse to disclose information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist any demands for information that would identify you, except as explained below. You should also know that there are several circumstances in which the Certificate does not provide coverage. These include when information:
x will be used for auditing or program evaluation internally by the NIH; or x must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA).
x is necessary for your medical treatment and you have consented to this disclosure; x is for other research.
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible as evidence or used for any purpose in any action, suit, or proceeding without your consent. You should understand that a Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
research. If an insurer, employer, or other person obtains your written consent to receive research information, then the researchers will not use the Certificate to withhold that information. The Certificate of Confidentiality will not protect against the required reporting by hospital staff of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others.
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NCT00069238
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Duration of Study Involvement
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What Happens After Treatment Is Completed:
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This depends on how you/your child have responded to the therapy. If all evidence of disease has disappeared, we will schedule periodic visits to the Clinical Center for follow-up examination and tests. If the disease gets worse while receiving therapy, does not disappear entirely or if it should recur after having disappeared for a period of time, then you/your child may need further therapy. At that time you/your child will be given the opportunity of participating in additional research protocols that may be appropriate for you/your child. If no such protocols are available, you/your child will be returned to the care of your/your child's local physician. It is important to stress that participation in this protocol does not constitute a promise of long-term medical care here at the Clinical Center. It is conceivable that participation in this study may make you/your child ineligible to participate in certain other research protocols because the requirements for entry onto these protocols may not allow patients who have already been treated with certain drugs or who have had certain side effects from previous treatment.
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
You/your child may decide now not to receive treatment on this protocol, or you/your child may choose at any point in time to stop the treatment and withdraw from the protocol; in either case you/your child will be returned to the care of your/your child's referring physician.
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NCT00069238
|
Participant's Rights
|
Research Subject'S Rights What Are The Costs Of Taking Part In This Study?
|
x You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
x There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.
x Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.
x Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
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NCT00069238
|
Possible Risks, Discomforts, and Inconveniences
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Risks Or Discomforts Of Participation|Side Effects That Have Been Observed With The Drugs In This Program When They Are Used Individually Include The Following:|Acute Infusion Reactions|Immune Suppression|Bone Marrow Toxicities|Miscellaneous Toxicities|Potential Benefits Of Participation
|
In order to determine whether this study is suitable for you/your child, a number of tests will have to be done. This period of evaluation may take up to two weeks and is usually done on an outpatient basis. Depending on the tests you/your child have already had before coming here, these may include blood and urine tests, studies of lung function, CAT or MRI scans, radioisotope scans, and biopsies of tumor tissue, bone marrow, liver, or other sites. As reviewed in the section above, you will undergo a lumbar puncture to remove a small amount of spinal fluid (about 1-2 teaspoons) that will be tested for the presence of lymphoma cells. A lumbar puncture is done by inserting a small sterile needle through the skin and muscle, going between the bones of the spine in the lower back until the needle punctures the spinal canal covering. The spinal fluid will then drain out through the needle on its own. Biopsies will, when possible, be done under local anesthesia. The risks associated with blood draws include pain, blood clots, bruises, infection and nerve damage. The risks associated with bone marrow biopsies include pain, bleeding, and infection. Risks of biopsies include pain, bleeding, infection, and the risks to the particular area undergoing surgery. General anesthesia itself is generally very safe but has a very small risk of major complications such as heart attack or stroke. The surgical and anesthetic risks will be explained to you/your child in more detail at the time of surgery, if this is needed. In order to receive this therapy you/your child will need to have an intravenous catheter placed. This catheter is usually placed in the arm, chest or neck area into a major vein inside your/your child's chest. We usually remove the catheter after each cycle but on occasion it can be left in for several cycles. The catheter is necessary for infusion of chemotherapy and for the drawing of blood. It is usually inserted under local anesthesia. The risks associated with the procedure include pain, bleeding, infection, and puncture of the underlying lung. Lung puncture can result in lung collapse, which might require that a chest tube be placed into the chest cavity (usually for a day or two) to help the lung reinflate. The long-term risks of the catheter include infection and clotting of the vein in which the catheter sits. If these occur, it may be necessary to remove the catheter. These risks will be explained to you/your child in more detail at the time of the insertion.
a. Doxorubicin may cause sore mouth, loss of hair, a fall in blood counts with increased risk of serious infection or bleeding, tissue damage if the drug contacts the skin, heart damage and, rarely, death due to heart failure. However, the infusion method used in this study has been shown to reduce the risk of heart damage compared to the standard rapid infusion method.
b. Cyclophosphamide may cause a fall in blood counts with increased risk of serious infection or bleeding, loss of hair, damage to the lining of the urinary bladder with painful and bloody urination, loss of function of the ovaries or testes, and nausea and vomiting. The bladder irritation can be minimized by drinking at least two quarts of fluid each day. Fluid retention with lowering of blood salt levels (known as SIADH) can rarely occur.
c. Vincristine often causes numbness of the hands and feet after several cycles. Patients also may have constipation and medications will be given to reduce this. In most instances, these symptoms resolve when the drug is stopped, but resolution of the numbness in the hands and feet may sometimes take months or even years. The drug can also cause tissue damage if it contacts the skin, low or high blood pressure, frequent or burning on urination, weight loss, rash, fever, headache, jaw pain and eye problems. Fluid retention with lowering of blood salt levels (known as SIADH) can rarely occur.
d. Etoposide may cause nausea and vomiting, diarrhea, loss of hair, lowering of blood pressure during administration, rash, itching, liver abnormalities, allergic reactions, mouth ulcers, and lowering of blood counts.
e. Alemtuzumab has a spectrum of side effects that can be divided into infusional reactions, immune suppression, bone marrow toxicity, and other side effects. These reactions are detailed below.
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
Some patients have reactions during the first few treatments that do not occur with later infusions of Alemtuzumab. The administration of Alemtuzumab can cause allergic reactions which may appear as shortness of breath or wheezing. If the shortness of breath becomes severe, you/your child may be required to have a tube placed in your/your child's throat to help you/your child breath. Other types of allergic-like possibilities include severe lowering of blood pressure, fever, chills, rash, hives, itching, or abdominal pain and throat swelling. Lowering of the blood pressure may cause damage to the heart or brain and this damage may be permanent. These reactions can be severe and some patients have died as a result of such reactions. You/your child will be given acetaminophen and diphenhydramine to reduce the severity of these side effects.
Your/your child's doctors or nurses will closely monitor you/your child closely throughout the treatment for these side effects.
The normal cells that fight infection in your/your child's body are killed by this treatment. Without these cells you/your child may develop infections that occur in patients whose immune system does not function. Patients treated with this drug can develop infection with viruses, fungi, parasites and bacteria. You/your child will be treated with oral medications to prevent certain infections and they will be continued until your/your child's doctors have determined that it is safe to discontinue them.
Many patients have had low blood counts when Alemtuzumab is given at the doses used in this trial. These effects are even more severe when Alemtuzumab is given to patients with bone marrow abnormalities. Anemia or a low red blood cell count, which causes weakness or fatigue has occurred and may require blood transfusion. Low platelet counts, which may cause a tendency to bleed, may require platelet transfusions and low white blood cell counts may make you/your child susceptible to infection. If the infection fighting white blood cells fall to low levels we may give you/your child G-CSF to stimulate the production of these cells. Occasional patients have had severe depression of all of the normal blood elements, a condition called aplasia.
Other common side effects include loss of appetite, nausea, vomiting, fatigue, headache, diarrhea, muscle or joint pain, ringing in the ears, difficulty with thinking, and damage to the liver. Blood pressure has been seen to increase following administration of Alemtuzumab and may require treatment. Your/your child body may react to the Alemtuzumab by making antibodies to it. These antibodies may rapidly inactivate the injected Alemtuzumab making it ineffective. Infections caused by organisms that normally inhabit your/your child body and cause no disease may become evident as a result of the treatment with Alemtuzumab. You/your child
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
may also be more susceptible to viral and bacterial infection. In addition the combination of Alemtuzumab and EPOCH chemotherapy may produce toxicities that are unknown. f. Prednisone may cause ulceration in the stomach or bowel, increased blood pressure, high blood sugar (diabetes), increased risk of infection, a round appearance of your/your child's face, weight gain, change in mood, thinning of your/your child's bones with increase in the risk of fracture, increased pressure in the eye (known as glaucoma) and clouding of the eye (called cataracts). It can also cause or worsen acne.
g. Filgrastim can occasionally cause bone pain by stimulating normal bone marrow. This stops when drug administration stops. It has also been reported sometimes to cause skin rash, skin reddening around the injection site, muscle cramps, decreased platelets (not clinically significant), pain or numbness and tingling around the chin, worsening of certain pre-existing inflammatory conditions (such as psoriasis eczema, or vasculitis), fever, body aches, and alterations in certain laboratory tests. With prolonged administration filgrastim has been associated with hair thinning and enlargement of the spleen. These side effects do not necessarily stop when drug treatment stops.
h. Trimethoprim/sulfamethoxazole can cause a skin rash that goes away when the drug is stopped. It is possible that the rash may not resolve and could indicate a severe reaction (i.e. Stevens-Johnson syndrome). If you/your child are allergic to this drug, you/your child will receive inhaled pentamidine instead. Inhaled pentamidine can cause coughing, wheezing, and burning pain in the throat. All of these symptoms usually go away shortly after the inhalation treatment is finished
i. Acyclovir can cause nausea/vomiting, diarrhea, headache, vertigo, insomina, irritability, depression, skin rash, acne. accelerated hair loss, arthralgia, fever, palpitations, sore throat, muscle cramps, menstrual abnormalities, and lymphadenopathy.
j. Fluconazole can cause nausea. Less common side effects may include: Abdominal pain, diarrhea, headache, skin rash, vomiting and elevated liver enzymes.
k. Methotrexate, when administered into the spinal fluid, may cause low blood counts and ulcerations in the mouth, stomach, and intestines. It can cause acute headache, back pain, stiff neck, and /or fever; it can also cause weakness or paralysis of certain muscles. It can cause seizures and coma. Other side effects it can cause are usually associated with intravenous administration rather than intrathecal (lumbar puncture administration), but these include liver function abnormalities, inflammation and scarring of the lungs, inflammation of the tissue covering the heart, and severe skin reactions.
l. Cytarabine given by lumber puncture can cause nausea, vomiting, fever, and headaches.
Rarely, it can cause weakness and seizures. When given into the spinal fluid, it does not usually cause systemic toxicity, but we will monitor you/your child for low blood counts, and liver function abnormalities, which can occur with cytarabine when given by vein.
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
It is important to emphasize that when you/your child have a decreased white blood cell count, you/your child are at risk of infection. Such infections can be very serious and can even cause death if not quickly and properly treated. Therefore, if you/your child have a temperature greater than 38.3° C (101° F), you/your child must call your doctor immediately. Chemotherapy may also cause your platelets to fall; since platelets are the blood elements that permit blood to clot, this may place you/your child at increased risk of serious bleeding. It may be necessary to give you/your child transfusions of platelets if your/your child's platelet counts reach very low levels. You/your child may also need red blood cell transfusions if your/your child's hemoglobin level drops very low. There is a small chance that damage to the normal bone marrow may eventually result in bone marrow failure, leading to a serious shortage of one or more kinds of cells in the blood, or to leukemia. Because this is a relatively new combination of drugs, it is always possible that unanticipated side effects may occur. Many of the drugs used in this treatment program are toxic to the cells in the ovary and testicle and may produce sterility. Recovery of normal fertility is not well studied although we know that some patients treated with this combination have remained fertile after the therapy has been completed. For this reason, men who are about to receive this treatment should, if they wish to have children in the future, consider sperm banking before start of the treatment. These drugs may also be very toxic to an unborn child. Therefore, adequate birth control measures (such as the contraceptive pill, condoms, diaphragm with contraceptive foam or ointment, contraceptive sponge, etc.) should be used by participants or their sexual partners while receiving treatment on this study. Women of childbearing age will have a pregnancy test, which must be negative at the time of study entry. This test requires that blood be drawn from a vein one or two days prior to the study. The results of the pregnancy test will be made available to you/your child prior to the initiation of the study. Your/your child's physicians will watch you/your child closely for side effects and will stop treatment if any side effects become a serious threat to your/your child's life or well-being. Your/your child's physicians will also stop the treatments if it becomes clear that the treatment is not successfully controlling your/your child's disease. Complications of Ommaya insertion are uncommon when done by an experienced group but could include infection and bleeding at the operative site or in the brain itself. Complications of lumbar puncture may include pain or bleeding at the site of needle insertion (the low back), infection, and headache. Most patients tolerate this treatment without serious side effects, although drugs placed into the brain fluid (CSF) may cause headache, stiff neck, and confusion that resolve when they are stopped. With long-term treatment, confusion and a slowing of thought processes may occur. If this treatment becomes necessary for you/your child, the complications of the lumbar puncture or Ommaya insertion and methotrexate instillation will be discussed in more detail.
It is likely that most patients will have at least a temporary improvement from treatment with Alemtuzumab and EPOCH chemotherapy. However, we cannot be certain if you/your child will
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
be cured of your/your child's lymphoma and it is possible that you/your child may not respond to treatment.
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NCT00069238
|
Procedures
|
Treatment Consists Of The Following Drugs:
|
1. Doxorubicin, etoposide, and vincristine - These three drugs are given by continuous IV
infusion over four days, beginning on day 1 and ending on day 5 of each cycle. We deliver these drugs with the aid of one lightweight, portable infusion pump, each about the size of a portable tape recorder; this permits treatment on an outpatient basis. The
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09) NIH-2514-2 (10-84)
P.A.: 09-25-0099
File in Section 4: Protocol Consent
pumps deliver the therapy through an intravenous catheter, which is placed in your/your
child's vein beforehand. You/your child will be taught about the use and care of the pump and what to do if it stops working.
2. Cyclophosphamide - This is given over about 15 minutes on day 5 of each treatment cycle.
3. Prednisone - These are pills given by mouth twice a day for the first 5 days of every cycle.
4. Alemtuzumab - Administered by vein over approximately twelve hours on the first day of therapy, immediately before the chemotherapy infusion begins.
5. Filgrastim - This is given by injection under the skin once a day starting on day 6 of each cycle and continuing until recovery of the white blood cell count or until day 19 of each cycle. If your/your child's white blood cell count is still very low on the day treatment is due to begin again, the chemotherapy may be deferred and the filgrastim will be given until you/your child have a fuller recovery of the white count. This drug is given to stimulate your/your child's bone marrow to produce neutrophils, one of your/your child's white blood cells. You/your child will be taught how to administer the filgrastim to yourself/your child during the first treatment cycle.
We expect that treatment will be given for 6 cycles (18 weeks), depending on how you/your child's respond to the therapy. In general you/your child will receive two cycles past the point of maximum response. Since several of these drugs can lower your/your child's resistance to infection, we also require that you/your child take a combination antibiotic, trimethoprim/sulfamethoxazole (SeptraR or BactrimR) for three days each week while you/your child are on chemotherapy, acyclovir (or an alternative drug) daily and fluconazole in an attempt to prevent infections. If allergic to these preparations, you/your child will be given other drugs with similar activities in their place.
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NCT00069238
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Purpose of Research
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Description Of Research Study|Objectives And Design Of This Study:|Treatment Of Disease In The Nervous System:
|
Lymphoma and its treatment: You/your child have a disease called T-cell or NK cell nonHodgkin's lymphoma which your/your child's doctors think would be better treated with chemotherapy than surgery or radiation. For your/your child's particular kind of non-Hodgkin's lymphoma, previous studies have shown that combinations of drugs are much more likely to make the disease go away for appreciable periods of time than single drugs, which have only very limited effectiveness against this group of lymphomas. Studies have also shown that more
PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH **STUDY**
- Adult Patient or - Parent, for Minor Patient
NIH-2514-1 (07-09)
P.A.: 09-25-0099 File in Section 4: Protocol Consent (1)
intensive (i.e. higher dose) treatments have a greater chance of success than more gentle approaches. In general, mature T-cell and NK cell lymphomas are less responsive to standard therapies than B-cell lymphomas. This protocol is specifically for people with T-cell and NK cell lymphomas, as we are trying to find better treatments for these types of lymphoma. Studies conducted at the National Cancer Institute suggest that certain chemotherapy drugs may be more effective if given by continuous infusion into the vein rather than by the standard method of rapid intravenous injection. One such combination, which we call EPOCH (each letter stands for one of the drugs used in the combination), seems to have a high degree of effectiveness in patients whose tumors have stopped responding to standard regimens. We therefore plan to test this combination in patients who have never received chemotherapy previously. Recent evidence also indicates that the effects of chemotherapy may be improved by combination with monoclonal antibodies. Monoclonal antibodies are purified proteins that are specially made to attach to pieces of foreign substances (such as cancer cells) with the goal of inactivating them. A monoclonal antibody, a drug called Alemtuzumab (the trade name is Campath-1H), has been manufactured to attach to a protein called CD52 that your/your child's type of tumor could contain. We will attempt to determine if your/your child's tumor "expresses" CD52, but you/your child will be eligible for treatment even if the results are unknown. Up to 30 patients will be treated on this study.
The general purpose of this study is to develop treatments for lymphoma that are more effective than existing therapies. The experimental part of this treatment program is to test whether giving alemtuzumab in combination with continuous infusion EPOCH chemotherapy with filgrastim is safe and if it improves the outcome of therapy of your/your child's lymphoma. In this study five chemotherapy drugs are given together in an intensive combination called EPOCH. Each series of treatments is called a cycle; a cycle is repeated every three weeks and drugs are administered during the first five days of every cycle. EPOCH consists of prednisone by mouth on days 1-5, and etoposide, doxorubicin, and vincristine as a continuous infusion on days 1 through 5 (total of 96 hours). In addition, cyclophosphamide is given by intravenous injection over about 15 minutes on day 5. You/your child will also receive a dose of alemtuzumab on day 1, immediately before the chemotherapy begins. Each cycle lasts 3 weeks: 5 days of chemotherapy followed by 16 days of no chemotherapy. You/your child will receive repeated cycles of Alemtuzumab and EPOCH until remission (disappearance of tumor) is achieved or until the tumor shows no further evidence of shrinkage. Between cycles of treatment we give another drug, filgrastim, whose purpose is to help your/your child's normal bone marrow cells recover from the chemotherapy and produce normal white cells. The use of filgrastim in this way may help us increase the total amount of chemotherapy you/your child can receive.
It occasionally happens that lymphomas spread to the coverings of the brain (the meninges) at some point during the illness. We will test to see whether there is any evidence of lymphoma in your brain or spinal fluid before you receive any treatment. If this should happen, the treatment usually includes the instillation of one of two chemotherapy drugs (methotrexate and cytarabine) directly into the fluid (the cerebrospinal fluid, or CSF) surrounding the brain. This is usually done by first placing a small reservoir (an Ommaya reservoir) under the skin of the scalp; this reservoir is connected to a catheter that is placed through the brain itself into the fluid. This procedure is performed by a neurosurgeon under general anesthesia. These drugs may also be administered through a spinal tap (also called a lumbar puncture). Depending on how you/your child responds to this therapy, it may be necessary to modify it and to also administer radiation to your/your child's brain and spinal cord. Each of these therapies will be discussed with you/your child if they are needed. Patients who have lymphoma in their bone marrow are at higher risk of developing lymphoma in the brain areas. To reduce this risk, patients at higher risk will receive methotrexate by a spinal tap on days 1 and 5 of cycles 3-6 of their EPOCH chemotherapy. Your/your child's treating physicians will discuss this with you/your child.
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NCT00104858
|
Alternatives
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➢ Are There Benefits To Taking Part In This Study?
|
The primary possible benefit is that it may provide an effective and potentially curative treatment for the patient's disease without the risks of treatment with high doses of radiation and chemotherapy. We cannot and do not guarantee the patient will benefit by taking part in this study. The treatment patients receive may even be harmful. Doctors feel that participation in this Page 11 study will give the patient at least as good a chance of surviving CLL as the patient might expect from other treatments. We hope the information learned from this study will benefit other patients with this type of leukemia in the future.
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NCT00104858
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Confidentiality
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➢ How Will Information About Me Be Kept Private? We Will Try To Keep Your Personal Information As Private As We Can. There Is No Guarantee Of
|
absolute privacy. Your personal information may be disclosed if required by law. Organizations that are listed below may inspect or copy your research records for quality assurance and data analysis. Your research records will identify you by name and will include things such as your medical history, results of your blood tests and exams, reports from your surgery and treatment, reports of your office visits.
➢ **Who may see my research information?**
In order to evaluate the results of the study, individuals from the Fred Hutchinson Cancer Research Center (FHCRC) may need to review medical records that identify you by name. These individuals include investigators directly involved in the study, institutional committees responsible for reviewing the safety and progress of studies, and members of the Institutional Review Board (this Committee is responsible for protecting the rights of persons taking part in research). In order to evaluate the results of this study, individuals from the National Cancer Institute might also need to review medical records that identify you by name. Your research records may be made available to the following organizations:
- The Fred Hutchinson Cancer Research Center (FHCRC)
- The University of Washington (UW)
- The Seattle Cancer Care Alliance (SCCA) - National Institutes of Health (NIH)
- Office for Human Research Protections (OHRP)
- The Food and Drug Administration (FDA)
- Institutional Review Board (IRB)
Your identity will not be revealed in any publication or presentation of results. Study records will be maintained indefinitely for the purpose of analysis and follow-up.
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NCT00104858
|
Duration of Study Involvement
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➢ How Long Will I Be In The Study?|➢ What Is Long-Term Follow-Up?
|
Your treatment will last approximately 3 and 1/2 months, but could be longer. You will be asked to return for follow up at 6 months and every year thereafter. We would like to keep track of your medical condition for the rest of your life to look at the long-term effects of the study. However, you may be taken off the protocol if one of the following happens:
- The study treatment does not work for your cancer;
- You develop a serious side effect that you cannot tolerate or that cannot be controlled with other medications;
- Your health gets worse;
- You are unable to meet the requirements of the study (for example, you cannot take the medicine as prescribed or you refuse follow-up);
- You start other treatments for your cancer; Page 5
- Other treatments for your cancer become available;
- Your request; Your decision to participate in this study is voluntary. You may decide not to participate in this study at any time, for any reason, without notice. However, early withdrawal from treatment during the conditioning regimen without subsequent stem cell transplantation could be fatal. The early discontinuation of the immune suppressing drugs, MMF and Cyclosporine, after blood stem cell transplant could lead to rejection of the donor blood stem cells or life threatening GVHD. We request that you discuss your decision with your primary doctor and if you wish the research physician prior to discontinuing the study.
We would like to keep track of your medical condition and health for the rest of your life to look at the long-term effects of the study. Long-term follow-up includes getting information useful for your medical care and research. Results of tests that are done after one year, as needed, help your referring physician plan your future care. We also get information for research by mailing questionnaires to you. The questionnaires will ask how you are doing and if you have any health problems. Research information is entered into our research database.
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NCT00104858
|
Participant's Rights
|
➢ What Are My Rights As A Study Participant?
|
Even after you agree to take part in this study, you may withdraw at any time. Before withdrawing, you should notify one of the people involved with this research. This will allow that person or someone else supervising the research to inform you of the medical risks associated with withdrawing. The medical risks may be substantial. You can choose to withdraw one of two ways. In the first, you can stop your study treatment, but still allow the study staff to follow your care. In the second, you can stop your study treatment and not have any further contact with the study staff. Either way, there will be no penalty or loss of benefits that you are already entitled to. Your decision will not affect your routine medical treatment, your relationship with those treating you, or your relationship with the study staff. If you withdraw from study therapy, you will still continue to receive medical care.
| ➢ | Who can I call if I have questions or problems? |
|-----------------------------------|-------------------------------------------------------------------------------------------------------|
| For Questions About | Please Contact |
| This study and what it involves | Your doctor (attending physician) or one of the investigators listed at the beginning of the consent |
| Your rights as a participant in a | Karen Hansen, in the Institutional Review Office, FHCRC |
| research study | at 206-667-4867 |
| Your bills and health insurance | Seattle Cancer Care Alliance, Patient Financial Services at |
| coverage | 206-288-1113 |
| Research use of your blood or | Clinical Research Division, Data Management Office, |
| tissue sample, or research files | FHCRC/Clinical Research Division at 206-667-4728 |
| Research related injury | Your physician or one of the investigators listed at the beginning of this consent |
| Emergency care | Emergency (24 hour) phone: (206) 598-8902 |
➢**What about use of my tissue/blood cells for research?**
An Institutional Review Board (IRB) must also approve any future or new research study using your tissue. The IRB is a group of people who review research studies to protect your rights. The research that may be done with your tissue is not designed to specifically help you. It might help people who have cancer and other diseases in the future. Reports about research done with your tissue will not be given to you or your doctor. These reports will not be put in your health records. The research using your tissue will not affect your care. Your tissue will be used only for research and will not be sold. The research done with your tissue may help to develop new products in the future, but you will not get paid. The possible benefits of research from your tissue include learning more about what causes cancer and other diseases, how to prevent them and how to treat them. The greatest risk to you is the release of information from your health records. The chance that this information will be given to someone else is very small.
➢ **Where can I get more information about cancer and its treatment?**
You can call the Cancer Information Service at 1-800-4-CANCER or visit the National Cancer Institute's Clinical Trials Web Site at http://cancertrials.nci.nih.gov. You can also get information at any time from the doctor in charge of your medical care in this study or one of the study investigators.
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