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IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 Appendix I CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form A Randomized Phase III Study of CC-5013 plus Dexamethasone versus CC-5013 plus Low Dose Dexamethasone in Multiple Myeloma with Thalidomide plus Dexamethasone Salvage Therapy for Non-Responders What is a research study? You are being asked to take part in this study because you have newly diagnosed multiple myeloma. This is a clinical trial (a type of research study). Clinical trials include only patients who choose to take part. Please take your time to make your decision and discuss it with your friends and family. Why is this study being done? This research is being done because current therapy does not help everyone with your disease and many of the commonly used therapies involve injections into the vein and significant side effects. 7/06 1/07 The purpose of this study is to find out what effects (good and bad) that the combination of CC-5013 (lenalidomide) plus dexamethasone has on you and your multiple myeloma. We are looking at different dose levels to see if a lower dose of dexamethasone gives the same benefit as a higher dose without as many side effects. After an adequate number of patients have been recruited to this portion of the study, we will study the efficacy of aspirin compared to a blood-thinner called coumadin in preventing blood clots (a common side-effect) among patients receiving CC-5013 with the higher dose of dexamethasone in the remaining patients. This is being done to see if the more powerful blood thinner coumadin can decrease the risk of blood clots better than aspirin. For patients in whom CC-5013 therapy does not work well, we will test the effect of switching from CC-5013 to thalidomide; while the drugs are chemically similar, they are not the same, and one may be more effective than the other in certain patients. 1/07 3/06 1/07 1/07 How many people will take part in the study? About 682 people will take part in this study. What is involved in the study? Please, first see the study plan on the last page of this form. We will be comparing a standard dose of dexamethasone with a low dose of dexamethasone when each is combined with CC-5013. After an adequate number of patients have been recruited to this portion of the study (approximately 412), we will study the efficacy of aspirin compared to a blood-thinner called coumadin in preventing blood clots (a common side-effect) among patients receiving CC-5013 with the higher dose of dexamethasone in the remaining (approximately 270) patients. 8/13/04 Page 1 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 Appendix I CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 1/07 1/07 1/07 ● CC-5013 is an investigational drug, not yet approved by the FDA, for the treatment of myeloma, which is chemically similar to thalidomide. In studies so far, CC-5013 has shown promising activity in advanced myeloma. Thalidomide is a drug which has recently shown promising benefit in patients with newly diagnosed and advanced myeloma. Thalidomide is considered an investigational drug when used for multiple myeloma; FDA approval for thalidomide use in myeloma treatment is pending. Dexamethasone is a type of steroid approved by the FDA for many diseases, and has been proven to be effective in both newly diagnosed and advanced myeloma. If you are in the first phase of the trial, you will be “randomized” into one of two study groups (Group A or Group B) described below in the section called “Procedures.” If you are in the second (expansion) phase of the trial, you will be randomized to one of two study groups (Group S or Group T). Randomization means that you are put into a treatment group by chance. You will have an equal chance of being placed in either group. It is similar to the flip of a coin. You and your doctor will NOT be able to choose which treatment you receive. If you take part in this study, you will have the following tests and procedures. Some of these tests would be done even if you do not take part in the study. Tests 1/07 Blood tests Urine tests Bone marrow biopsy X-rays While you are receiving treatment your blood and urine tests will be repeated once a month to assess the effect of treatment on your myeloma. Once you have completed 4 months of treatment we will also repeat the bone marrow biopsy and bone x-rays to assess the effect of treatment. Procedures Group A: If you are assigned to Group A you will be treated with CC-5013 and standard dose dexamethasone. You will take 25 mg of CC-5013 once a day, for 21 days (days 1-21), and then have one week off with no CC-5013 (days 22-28). This 28-day period is considered "one cycle." You will take 40 mg of dexamethasone daily on days 1-4, 9-12, and 17-20 of this 28-day cycle in addition to CC-5013. If there are no signs to suggest worsening of your myeloma, you will receive 4 "cycles" of this treatment, lasting a total 8/13/04 Page 2 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 11/05 3/06, 1/07 of 16 weeks. You will receive one aspirin per day (325mg) while receiving this treatment, to prevent complications known to be caused by both your myeloma and the treatment drugs. Specifically, the complications involve blood clots in the legs and lungs. If you notice swelling in your legs, contact your doctor immediately. Your doctor may choose to use other drugs to prevent these complications instead of aspirin. Further therapy will be at your doctor’s discretion, but if you responded well to CC-5013, you will have the option to continue receiving CC-5013 with dexamethasone as on this protocol until your myeloma shows signs of worsening. If you do continue therapy beyond 4 cycles, the dose of dexamethasone will be reduced to days 1-4 every 28 days. Group S: If you are assigned to Group S, you will be treated with CC-5013 and 1/07 standard dose dexamethasone. You will take 25 mg of CC-5013 once a day, for 21 days (days 1-21), and then have one week off with no CC-5013 (days 22-28). This 28day period is considered "one cycle." You will take 40 mg of dexamethasone daily on 1/07 days 1-4, 9-12, 17-20 of this 28-day cycle in addition to CC-5013. If there are no signs to suggest worsening of your myeloma, you will receive 4 "cycles" of this treatment, 11/05 lasting a total of 16 weeks. You will receive one aspirin per day (325mg) while receiving this treatment, to prevent complications known to be caused by both your myeloma and the treatment drugs. Specifically, the complications involve blood clots in the legs and 11/05,1/07 lungs. If you notice swelling in your legs, contact your doctor immediately. Further therapy will be at your doctor’s discretion, but if you responded well to CC-5013, you will have the option to continue receiving CC-5013 with dexamethasone as on this 3/06,1/07 protocol until your myeloma shows signs of worsening. If you do continue therapy beyond 4 cycles, the dose of dexamethasone will be reduced to days 1-4 every 28 days. 1/07 1/07 1/07 Group T: If you are assigned to Group T you will be treated with CC-5013 and standard dose dexamethasone. You will take 25 mg of CC-5013 once a day, for 21 days (days 1-21), and then have one week off with no CC-5013 (days 22-28). This 28-day period is considered "one cycle." You will take 40 mg of dexamethasone daily on days 1-4, 9-12, and 17-20 of this 28-day cycle in addition to CC-5013. If there are no signs to suggest worsening of your myeloma, you will receive 4 "cycles" of this treatment, lasting a total of 16 weeks. You will receive coumadin (a commonly used blood thinner) while receiving this treatment, to prevent complications known to be caused by both your myeloma and the treatment drugs. Specifically, the complications involve blood clots in the legs and lungs. If you notice swelling in your legs, contact your doctor immediately. Further therapy will be at your doctor’s discretion, but if you responded well to CC-5013, you will have the option to continue receiving CC-5013 with dexamethasone as on this protocol until your myeloma shows signs of worsening. If you do continue therapy beyond 4 cycles, the dose of dexamethasone will be reduced to days 1-4 every 28 days. If you have not had any blood clotting issues during the first 4 cycles, you will stop taking coumadin and take aspirin, instead, for the same purpose of preventing blood clots. 8/13/04 Page 2 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 1/07 11/05 3/06 11/05 3/06 1/07 Group B: If you are assigned to Group B you will be treated with CC-5013 and low dose dexamethasone. You will take 25 mg of CC-5013 once a day, for 21 days (days 1-21), and then have one week off with no CC-5013 (days 22-28). This 28-day period is considered "one cycle." You will take 40 mg of dexamethasone daily on days 1, 8, 15 and 22 of this 28-day cycle in addition to CC-5013. If there are no signs to suggest worsening of your myeloma, you will receive 4 "cycles" of this treatment, lasting a total of 16 weeks. You will receive one aspirin per day (325 mg) while receiving this treatment, to prevent complications known to be caused by both your myeloma and the treatment drugs. Specifically, the complications involve blood clots in the legs and lungs. If you notice swelling in your legs, contact your doctor immediately. Your doctor may choose to use other drugs to prevent these complications instead of aspirin. Further therapy will be at your doctor’s discretion, but if you responded well to CC-5013, you will have the option to continue receiving CC-5013 with dexamethasone as on this protocol until your myeloma shows signs of worsening. Groups C and D: Groups C and D are only for patients who have not responded adequately to therapy on Group A or B by the end of 4 cycles. This means you will not automatically join Group C or D when you finish your Group A or Group B treatment. If you meet the criteria to join this second step, you will register to it and begin the new treatment within 5 days of ending your Group A or B treatment. Group A patients may register to Group C and Group B patients may register to Group D. If you enter Group C or D, you will be treated with thalidomide and dexamethasone. You will take 200 mg thalidomide once a day, at night for 28 days (four weeks). This 28-day period is considered "one cycle." You will take dexamethasone at the same dosage as you received in Groups A or B during this 28-day cycle in addition to thalidomide. You will continue to receive aspirin or a drug of your doctors choice to prevent blood clots. If there are no signs to suggest worsening of your myeloma, you will receive 4 "cycles" of this treatment, lasting a total of 16 weeks. Further therapy will be at your doctor’s discretion, but if you responded well to thalidomide, you will have the option to continue receiving thalidomide with dexamethasone as on this protocol until your myeloma shows signs of worsening. Patients who choose to continue protocol treatment after 4 cycles of treatment on Group C will begin to receive less dexamethasone (on days 1-4 of each cycle only). This is similar to the Group D dose schedule. Researchers think it will reduce the chance of blood clots. The Investigator enrolling you on the study treatment will provide you with a patient diary. You will mark in the patient diary the date and exact number of pills taken and any comments you might have regarding side effects. The diary will be used by your doctor to make sure you are taking the medications correctly. 3/06 How Long Will I Be in the Study? We think you will be on the study treatment for at least 4 months; if you respond well to treatment, you may continue treatment until your disease shows signs of worsening, at the discretion of your treating doctor. If you do not respond well during the first 4 months, you may also need 4 more months of therapy in Group C or D. If you respond 8/13/04 Page 3 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 3/06 well in Group C or D, you may continue treatment until your disease shows signs of worsening. Alternatively, you may be on the study treatment for less than 4 months if your multiple myeloma worsens. Once you complete the study, we would like to keep track of your medical condition for 7 years to look at the long-term effects of the study. Your doctor may decide to take you off this study treatment if you have excessive side effects, if your condition worsens, if new information is available, or for any reason felt to be in your best interests. You may stop participating at any time. However, if you decide to stop participating in the study, we encourage you to talk to your doctor first. What Are the Risks of the Study? While on the study, you are at risk for the following side effects. CC-5013 or thalidomide or dexamethasone may cause some, all or none of the side effects listed. You should discuss these with your doctor. There may also be other side effects that we cannot predict. Other drugs will be given to make side effects less serious and less uncomfortable. Many side effects go away shortly after thalidomide and dexamethasone are stopped, but in some cases side effects can be serious, longlasting, permanent, or life threatening. Death is rare, but possible. Your doctor will check you closely to see if any of these side effects are occurring and routine blood tests will be done to monitor the effects of treatment. 1/07 Risks and side effects related to the CC-5013 plus dexamethasone regimens we are studying in Groups A, B, S and T include: Likely: 1/07 11/05 3/06 Blood abnormalities, such as a decrease in the number of white blood cells, red blood cells, platelet, and/or neutrophils. White blood cells are cells of your immune system. A decrease in white blood cells and or neutrophils may lead to fever and/or a life threatening infection. The red blood cells carry oxygen to your organs. A decrease in red blood cells can lead to fatigue. A decrease in platelets may lead to bleeding and require stopping treatment. An elevated number of eosinophils, a type of white blood cell, may also be seen. A decrease in another type of white blood cells may increase the risk of rare types of infections, called opportunistic infections. • Blood clots. These can be life threatening because they can dislodge and go to the lungs. Recently, participants in this research study who were being treated with CC-5013 and the standard dose of dexamethasone were found to be 4 to 5 times more likely to have blood clots develop in their legs and lungs. There were more blood clots in this group than those who were treated with CC-5013 and the lower dose of dexamethasone. Because of this, you will be asked to take an aspirin tablet (325mg) once a day along with your treatment for the myeloma. 8/13/04 Page 4 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 3/06 3/06 3/06 3/06 Or, your doctor may decide to use some other anti-coagulation treatment, such as warfarin (Coumadin), or enoxaparin (Lovenox). If you are treated with warfarin or enoxaparin, you will not take the daily aspirin tablet. The risks of blood clots may be higher when CC-5013 is taken along with erythropoietin, a drug sometimes given to help keep blood counts normal during treatment. • Skin rash which could be hives, welts or acne-like • Fever with chills • Fatigue with light headedness, dizziness or fainting 3/06 3/06 3/06 Headache Stomach and throat ulcers or worsening or irritation of existing ulcers Increased weight around the stomach Puffiness (especially in the face) Retaining of salt and fluids which could cause an increase in blood pressure A rise in the blood sugar, which may make you feel weak, tired and thirsty. You may have difficulty thinking, palpitations, or loss of memory. Rarely, comas or seizures may occur. Problems with the level of potassium in the blood. This may make you feel weak and tired. Rarely, there may be irregular heartbeat or sudden death. Muscle weakness Brittle bones Menstrual changes Mood swings Trouble with sleeping Changes in personality • Weight gain or loss Weakening of the immune system resulting in an increased risk of infections, which may be life-threatening • Pneumonia (an infection in your lungs) Tremors • Sweating 11/05,3/06 Less Likely Tumor lysis syndrome (a syndrome in which uric acid, potassium, and phosphate are released into the blood as a result of tumor breakdown following administration of the study drug). High levels of uric acid, potassium and phosphate may negatively affect cardiac function and/or may result in poor kidney function. 8/13/04 Page 5 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 3/06 Worsening heart function. You may feel weak and short of breath. Leg swelling or collection of fluid in various areas of your body may occur. Rarely there is a risk of irregular heartbeat or sudden death. Abnormally fast or irregular heart beats Heart attack which can be life threatening Stroke which can be life threatening • High or low blood pressure 3/06 • Symptoms of hay fever such as sneezing, nasal stuffiness and post nasal drip 3/06 3/06 3/06 3/06 3/06 3/06 3/06 3/06 3/06 3/06 3/06 3/06 3/06 3/06 7/06 3/06, 1/07 3/06 3/06 3/06 3/06 3/06 Seizures (Convulsions) Cellulitis (a spreading infection/swelling within the tissue under the skin) Inflammation of the pancreas Loss of appetite • Confusion • • • • • • • • • • • Dizziness Passing gas Upset stomach or heartburn Swelling of the feet, legs, hands, and arms Increase in blood test that indicate the kidneys may be functioning abnormally Alteration in taste or loss of taste Dehydration Nausea Vomiting Dry skin Pain in the abdomen, back, bone, chest, head, muscle, gums or other places in the body Joint pain from arthritis • • Swelling of the sinuses • Diarrhea Rare, but serious: • • • • • Fluid in the membrane that surrounds the lungs causing difficulty breathing Kidney failure Damage to the kidneys Urge to urinate frequently or urgently Vision changes such as blurry vision, flashing lights or floaters 8/13/04 Page 6 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 3/06 3/06 3/06 3/06 3/06 3/06 • • • • Dry eyes Damage to the retina of the eye Obstruction of the lower intestines that causes severe constipation Development of a hole in the lower intestine that causes a life-threatening infection of the abdomen • Hair loss either on the scalp or the rest of the body • Increased sensitivity of the skin to the sun that could result in more severe sunburns 3/06 • Chest pain that could indicate the risk for a future heart attack 1/07 3/06 3/06 3/06 3/06 3/06 High levels of uric acid in your blood. You may develop severe joint swelling or problems passing urine because of a kidney stone or kidney failure. ● Decrease or increase in the amount of thyroid hormone • Decrease in the amount of testosterone hormone • • • • 3/06 • 3/06 • 3/06 • • Difficulty in thinking clearly Alterations in mood such as feeling agitated, anxious or depressed Experiencing hallucinations or experiencing thoughts that are not based in reality Fainting Lowered level of awareness Difficulty breathing Difficulty with normal speech Swelling of the spinal cord (myelitis) Leg and hand cramps Numbness and tingling, which may be painful Damage to the nerves Worsening of liver function: you may have yellow discoloration of your eyes and skin, swelling of the belly and legs, worsening mental function or even coma, vomiting blood or passing blood during bowel movements. Back pain Itchy eyes Blurry vision Constipation or diarrhea Bloated abdomen Cough Bleeding in the brain, genitourinary, or lungs that could be life-threatening Increased blood clotting time with increased risk of bleeding 8/13/04 Page 7 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 3/06 1/07 • Abnormalities in proteins that regulate blood clotting that could result in either bleeding or blood clots Ringing in the ears Inflammation at the back of the mouth and/or tongue Night sweats Anemia caused by the breakdown of blood cells ● Itching, and other allergic reactions (including severe allergic reactions with fevers) Participants with glaucoma or a family history of glaucoma may experience a rise of inner eye pressure or glaucoma Dexamethasone given for more than one year at doses of 15 mg or greater may cause cataracts Dexamethasone may also affect the skin by causing stretch marks (stomach, lower back, breasts, and groin area). Slow wound healing Increased sweating Easy bruising Continued use of dexamethasone (more than 25 mg for 2 weeks) can lower the function of the adrenal glands. This drug may also alter the body's defense system increasing the chance of infections. There may be a risk of added toxicity when dexamethasone is combined with CC-5013. Risks and side effects related to the thalidomide plus dexamethasone regimens we are studying in Groups C and D include: Likely Sleepiness: To minimize the effects of sleepiness on your life, the drug is administered at night. Alcohol or sleeping pills can increase the effects of sleepiness or other side affects and must not be taken while on thalidomide. You should discuss this with your doctor Trouble sleeping Rash Nerve damage which may cause permanent inability to use an arm or leg, hearing loss, or loss of sensation, persistent numbness and tingling Constipation: To avoid constipation a regular program of stool softeners is recommended Low white cell count, which may put you at risk for a life-threatening infection Fatigue Thyroid problems 8/13/04 Page 8 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Heart beat irregularities, slow heart beat Worsening heart function. You may feel weak and short of breath. Leg swelling or collection of fluid in various areas of your body may occur. Rarely there is a risk of irregular heartbeat or sudden death. Blood irregularities, such as anemia (“low blood”) Breathing difficulties Decreased sex drive Stomach and throat ulcers or worsening or irritation of existing ulcers Inflammation of the pancreas Increased weight around the stomach Puffiness (especially in the face) Retaining of salt and fluids which could cause an increase in blood pressure A rise in the blood sugar, which may make you feel weak, tired and thirsty. You may have difficulty thinking, palpitations, or loss of memory. Rarely, comas or seizures may occur. Problems with the level of potassium in the blood. This may make you feel weak and tired. Rarely, there may be irregular heartbeat or sudden death. Muscle weakness Brittle bones Menstrual changes Mood swings Depression Changes in personality, confusion Weight gain Weakening of the immune system resulting in increased risk of infections, which may be life-threatening Pneumonia (swelling in your lungs) Dry skin, itching Swelling of feet Tremors Less Likely Seizures (convulsions) Blood clots in legs. These can be life threatening because they can dislodge and go to the lungs. To prevent blood clots your doctor may prescribe a blood thinner usually given as an injection under the skin daily while you receive thalidomide. Heart attack, which can be life threatening Severe/life threatening skin rash 8/13/04 Page 9 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Pancreatitis Decrease in blood supply to the brain (stroke), which can be life threatening Kidney damage A spreading infection/swelling within the tissue under the skin Rare, but Serious Dry mouth Headache Increased appetite Milky nipple discharge Coordination difficulties while walking Low platelets (may make you more likely to have bruising or bleeding) Inflammation of the eye Intestinal obstruction Hepatitis Decrease in blood pressure when standing quickly Lightheadedness, dizziness or fainting Bone pain Hair Loss Nausea, vomiting Participants with glaucoma or a family history of glaucoma may experience a rise of inner eye pressure or glaucoma Dexamethasone given for more than one year at doses of 15 mg or greater may cause cataracts Dexamethasone may also affect the skin by causing stretch marks (stomach, lower back, breasts, and groin area) Slow wound healing Increased sweating Easy bruising Continued use of dexamethasone (more than 25 mg for 2 weeks) can lower the function of the adrenal glands Dexamethasone may also alter the body's defense system increasing the chance of infections Skin rashes with thalidomide are usually mild, but serious dermatologic reactions including Stevens-Johnson Syndrome (a severe and sometimes fatal form of a skin disease consisting of a rash or lesions and reddening or discoloration of the skin that often results in blindness), which may be fatal, have been reported. THALOMIDTM (thalidomide) should be stopped if a skin rash occurs and only 8/13/04 Page 10 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form resumed after your doctor has checked your rash. If the rash causes the skin to shed, become blotchy, or blister, or if Stevens-Johnson Syndrome or infectious deadening of skin is suspected, use of thalidomide should not be resumed Thalidomide may interact with certain drugs such as anti-seizure medications, barbiturates, and alcohol. You must not take barbiturates or drink alcohol while taking thalidomide. Use caution when driving or operating machinery There may be a risk of added toxicity when dexamethasone is combined with thalidomide There is an increased risk of kidney damage when thalidomide is combined with bisphosphonates (drugs commonly given as supportive care for myeloma) Secondary Malignancies: A number of established chemotherapeutic drugs have an inherent (basic) risk of causing secondary cancers and/or leukemias (cancer of the white blood cells). Certain drugs in use today, not currently known to be associated with this risk, may be shown at a later time to result in the development of these secondary cancers and/or leukemias, which may not be reversible. Reproductive Risks of CC-5013 and Thalidomide You should not become pregnant or father a baby while on this study. You should not breastfeed your baby while on this study. The following contraceptive methods are mandatory. If you are a woman of childbearing potential, you must refrain from sexual intercourse or employ two methods of contraception: one of which is highly effective (IUD, birth control pills, tubal ligation or partner’s vasectomy) and another additional method (condom, diaphragm or cervical cap). Women who have had a hysterectomy or have been postmenopausal and have had no period for at least 24 consecutive months do not have to use the described contraceptive measures. 7/06 Men must be informed and understand the risk of birth defects. If you are a man, you must agree to use latex condoms every time you have sex with a woman while taking lenalidomide and thalidomide and for 4 weeks after you stop taking the drug even if you have had a successful vasectomy. 7/06 Thalidomide is known to be present in the semen of men treated with thalidomide (it is currently unknown if CC-5013 is present in the semen of men taking CC-5013). You must tell the doctor if you have sex with a woman without using a latex condom, or if you think for any reason that your partner may be pregnant. You must NOT be a sperm or blood donor while being treated with lenalidomide or thalidomide. 8/13/04 Page 11 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 7/06 1/07 7/06 Women who are still having periods and can become pregnant must have a pregnancy test conducted by the doctor before taking part in this study. If you are pregnant, you cannot take CC-5013 or thalidomide. The pregnancy test is performed on blood drawn from a vein 28 days prior to starting therapy and then another one within 24 hours before the start of CC-5013 (lenalidomide) or thalidomide. You must have a pregnancy test done by the doctor every week during the first 4 weeks of treatment. You will then have a pregnancy test every 4 weeks if your periods are regular or every 2 weeks if your cycles are not regular. You may also need to have a pregnancy test if you miss your period or have unusual menstrual bleeding while on this study. If the pregnancy test is positive, you will not be able to take part in the study. You will be told the results of the pregnancy test. You must not breast-feed a baby while being treated with lenalidomide. You must NEVER donate blood or ova while being treated with lenalidomide. Lenalidomide does not induce abortion of the fetus and should never be used for contraception. Thalidomide causes severe birth defects in unborn babies if females who are pregnant take it. The risk of thalidomide causing damage to the embryo is up to 50% for females taking thalidomide during the “sensitive period,” which is estimated to range from 35-50 days after the last menstrual period. It is not known whether thalidomide may cause birth defects in unborn babies if it is taken after the “sensitive’ period". A single dose of thalidomide may cause birth defects. Because CC-5013 is a close relative of thalidomide, similar risks may exist with this drug as well. In animal studies so far, there have been no birth defects associated with CC-5013, but we are being cautious because CC-5013 is chemically very similar to thalidomide. Birth defects observed in babies exposed to thalidomide during pregnancy include absent or abnormal legs and arms; spinal cord defects; cleft lip or palate; absent or abnormal external ear; heart, kidney, and genital abnormalities; and abnormal formation of the digestive system, including blockage of necessary openings. A 1994 article by Stromland and others describes an association between thalidomide and autism. Because of the severity of these abnormalities, it is extremely important that pregnancies do not occur while you are taking CC-5013 or thalidomide. You should discuss with your doctor what the best methods of birth control are for you. Remember, however, that no method of birth control besides complete abstinence provides 100% protection from pregnancy. Patients with a history of infertility should still take the appropriate contraceptive measures. 8/13/04 Page 12 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Important Information and Warnings for All Patients Taking CC-5013 or Thalidomide Warning: Serious Human Birth Defects If CC-5013 or Thalidomide ARE taken during pregnancy, it can cause severe birth defects or death to an unborn baby. CC-5013 and Thalidomide should never be used by women who are pregnant or who could become pregnant while taking the drug. Even a single dose taken by a pregnant woman can cause severe birth defects. CONSENT FOR WOMEN: INIT: 1. I understand I must not take CC-5013 or THALOMID™ (thalidomide) if I am pregnant, breast-feeding a baby, or able to get pregnant and not using the required two methods of birth control. INIT: 2. I understand that severe birth defects can occur with the use of CC-5013 or THALOMID™ (thalidomide). I have been warned by my doctor that my unborn baby will almost certainly have serious birth defects or may even die if I am pregnant or become pregnant while taking CC-5013 or THALOMID™ (thalidomide). INIT: 3. I understand that if I am able to become pregnant, I must use at least one highly effective method and one additional effective method of birth control (contraception) AT THE SAME TIME: At least one highly effective method AND IUD Hormonal (birth control pills, injections, or implants) Tubal ligation Partner’s vasectomy One additional Method Latex condom Diaphragm Cervical cap These birth control methods must be used for at least 4 weeks before starting CC-5013 or THALOMID™ (thalidomide) therapy, all during CC-5013 or THALOMID™ (thalidomide) therapy, and for at least 4 weeks after CC-5013 or THALOMID™ (thalidomide) therapy has stopped. I must use these methods even if I am infertile, unless I have had a hysterectomy or because I have been post-menopausal for at least 24 months (been through the changes of life). The only exception is if I completely avoid heterosexual intercourse. If a hormonal (birth control pills, injections, or implants) or IUD method is not medically possible for me, I may use another highly effective method or two barrier methods AT THE SAME TIME. INIT: 4. I know that I must have a pregnancy test done by my doctor within 28 days prior to registration, within the 24 hours prior to starting CC-5013 or THALOMID™ (thalidomide) therapy, then every week during the first 4 weeks of CC-5013 or THALOMID™ (thalidomide) therapy. I will then have a pregnancy test every 4 weeks if I 8/13/04 Page 13 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form have regular menstrual cycles, or every 2 weeks if my cycles are irregular while I am taking CC-5013 or THALOMID™ (thalidomide). INIT: 5. I know that I must immediately stop taking CC-5013 or THALOMID™ (thalidomide) and inform my doctor if I become pregnant while taking the drug; if I miss my menstrual period, or experience unusual bleeding; stop using birth control; or think, FOR ANY REASON, that I may be pregnant. If my doctor is not available, I can call 1888-668-2528 for information on emergency contraception. INIT: 6. I am not now pregnant, nor will I try to become pregnant for at least 4 weeks after I have completely finished taking CC-5013 or THALOMID™ (thalidomide). INIT: 7. I understand that CC-5013 or THALOMID™ (thalidomide) will be prescribed ONLY for me. I must NOT share it with ANYONE, even someone who has symptoms similar to mine. It must be kept out of the reach of children and should never be given to women who are able to have children. INIT: 8. I understand CC-5013 or THALOMID™ (thalidomide) can cause side effects including nerve damage (numbness, tingling or pain in the hands of feet that may not be reversible) and drowsiness. (If I become drowsy, I will not operate heavy machinery or drive a car. Also, I will avoid alcohol and other medicines not prescribed by my doctor). If I develop a red itchy rash I will contact my doctor immediately. If I feel dizzy, I will sit upright for a few minutes before standing up from a lying or sitting position. I understand all of the other possible side effects explained to me by my doctor. I know that I cannot donate blood while taking CC-5013 or THALOMID™ (thalidomide). INIT: 9. My doctor has answered any questions I have asked. CONSENT FOR MEN: INIT: 1. I understand that I must not take CC-5013 or THALOMID™ (thalidomide) if I cannot avoid unprotected sex with a woman, even if I have had a successful vasectomy. INIT: 2. I understand that severe birth defects or death to an unborn baby have occurred when women took thalidomide during pregnancy. INIT: 3. My doctor has told me that I must NEVER have unprotected sex with a woman because it is not known if the drug is present in semen or sperm. My doctor has explained that I must either completely avoid heterosexual sexual intercourse or I must use a latex condom EVERY TIME I have sexual intercourse with a female partner while I am taking CC-5013 or THALOMID™ (thalidomide) - and for 4 weeks after I stop taking the drug, even if I have had a successful vasectomy. INIT: 4. I also know that I must inform my doctor if I have had unprotected sex with a woman; or if I think, FOR ANY REASON, that my sexual partner may be pregnant. If my doctor is not available, I can call 1-888-668-2528 for information on emergency contraception. 8/13/04 Page 14 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form INIT: 5. I understand that CC-5013 or THALOMID™ (thalidomide) will be prescribed ONLY for me. I must NOT share it with ANYONE, even someone who has symptoms similar to mine. It must be kept out of the reach of children and should never be given to women who are unable to have children. INIT: 6. I understand CC-5013 or THALOMID™ (thalidomide) can cause side effects including nerve damage (numbness, tingling or pain in the hands of feet that may not be reversible) and drowsiness. (If I become drowsy, I will not operate heavy machinery or drive a car. Also, I will avoid alcohol and other medicines not prescribed by my doctor). If I develop a red itchy rash I will contact my doctor immediately. If I feel dizzy, I will sit upright for a few minutes before standing up from a lying or sitting position. I understand all of the other possible side effects explained to me by my doctor. I know that I cannot donate blood while taking CC-5013 or THALOMID™ (thalidomide). INIT: 7. My doctor has answered any questions I have asked. Authorization: In the Signatures section of this form, you will be asked to verify that this information has been read aloud to you, that you understand that if you do not follow all of your doctor’s instructions you will not receive CC-5013 or thalidomide, and that you authorize your doctor to begin treatment with CC-5013 or thalidomide. 1/07 1/07 Risks of supportive care therapy As part of standard supportive care for myeloma you will most likely be receiving drugs such as pamidronate or zoledronic acid to strengthen your bones. There may be an increased risk of kidney problems when these drugs are used along with thalidomide or CC-5013. You will be monitored for kidney problems before each pamidronate or zoledronic acid treatment you receive. Also the main risks of aspirin and the blood thinner coumadin are bleeding complications which can be serious or life-threatening. The risk of bleeding complications may be greater in patients receiving coumadin compared to aspirin. Risks of Bone Marrow Tests: There may be infection, bleeding or bruising at the site of the bone marrow biopsy or aspiration, as well as possible inflammation of the vein or infection. A bone marrow aspiration is a procedure in which an area of the hip is numbed and a small sample of bone marrow fluid is withdrawn. A bone marrow biopsy is similar except a sample of bone marrow tissue is removed through the needle. There may be temporary pain or discomfort at the bone marrow site. However, a local anesthetic is routinely used to numb the skin, and care will be taken to avoid these complications. Bone marrow studies carry very minimal risk to the patient. 8/13/04 Page 15 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Are There Benefits to Taking Part in the Study? If you agree to take part in this study, there may or may not be direct medical benefit to you. Possible benefits include improvement in the symptoms related to your cancer, and prolonged survival. We hope the information learned from this study will benefit other patients' myeloma in the future. What Other Options Are There? Instead of being in this study, you have these options: Chemotherapy with vincristine, adriamycin and dexamethasone Chemotherapy with melphalan and prednisone Therapy with dexamethasone alone Therapy with thalidomide plus dexamethasone Comfort care only, where treatments are directed only at reducing symptoms, relieving suffering, and maximizing comfort, dignity, and control. In comfort care only, treatment is not directed at curing, slowing or reversing your disease. Please talk to your doctor about these and other options. Will my medical information be kept private? This study is being conducted by the Eastern Cooperative Oncology Group (ECOG). ECOG is a cancer group that conducts studies for the National Cancer Institute. To help protect your privacy, ECOG has obtained a Confidentiality Certificate from the Department of Health and Human Services (DHHS). With this Certificate, ECOG cannot be forced (for example, by court subpoena) to disclose 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 the Department of Health and Human Services 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 ECOG 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 your doctor and ECOG are not prevented from taking steps, including reporting to authorities, to prevent serious harm to yourself or 8/13/04 Page 16 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form others, and the Certificate does not prevent the review of your research records under some circumstances by certain organizations for an internal program audit or evaluation. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used. A record of your progress will be kept in a confidential form at your hospital or doctor’s office where you receive treatment. Organizations that may inspect and/or copy your research and medical records (blood samples, x-rays, scans, pathology slides, etc.) for quality assurance, research, and data analysis include groups such as: Southeast Cancer Control Consortium (SCCC) Operations Office Cancer Trials Support Unit (CTSU) and its representatives Eastern Cooperative Oncology Group (ECOG) National Cancer Institute (NCI) and its representatives Food and Drug Administration (FDA) Office for Human Research Protections (OHRP) Institutional Review Board (IRB) at your hospital A qualified representative of applicable drug manufacturers, distributors, and/or their representatives Other regulatory agencies and/or their designated representatives Designated laboratories and reviewers If your record is used or given out for governmental purposes, it will be done under conditions that will protect your privacy to the fullest extent possible consistent with laws relating to public disclosure of information and law-enforcement responsibilities of the agency. These agencies may review the research to see that it is being done safely and correctly. You authorize the use of clinical information contained in your records, but any publication which includes such information or data shall not reveal your name, show your picture or contain any other personally identifying information, except as otherwise required by law. 1/07 3/06 What are the costs of taking part in this study? The Division of Cancer Treatment, and Diagnosis, NCI will provide you with the NCI sponsored/supplied agents (CC-5013 for Groups A, B, S and T, thalidomide if you need to register to Groups C or D) free of charge for this study. If you respond well to CC-5013 treatment, CC-5013 may be provided until your myeloma shows signs of worsening. If you do not respond well to CC-5013, but do respond well to thalidomide, 3/06 thalidomide will be provided until your myeloma shows signs of worsening. Every effort will be made to ensure adequate supplies of the sponsored/supplied agents, free of charge, for all participants. If the drug becomes commercially available for this indication there is a remote possibility that you may be asked to purchase subsequent supplies. Your doctor will discuss this with you should this situation arise. 8/13/04 Page 17 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form 3/06 The aspirin which is used to prevent blood clots is available over the counter, and will be paid for by you. If your doctor prescribes alternate medications, they will be billed to your insurance. Please discuss this with your doctor. You and/or your health plan/insurance provider (Medicare should be considered a health insurance provider) will need to pay for some or all of the costs of treating your cancer in this study. Some health plans will not pay these costs for people taking part in studies. Check with your health plan or insurance company to find out what they will pay for. Taking part in this study may or may not cost your insurance company more than the cost of getting regular cancer treatment. You or your insurance carrier will be responsible for the costs of clinic visits, any hospital admissions, laboratory tests, xrays, scans, chemotherapy treatments, radiation treatments, and any other tests. Please ask your doctor about any added costs or insurance problems. In the case of injury or illness resulting from this study, emergency medical treatment is available but will be provided at the usual charge. No funds have been set aside to compensate you in the event of injury. 7/06 What are my rights if I take part in this study? Even after you agree to take part in this study, you may withdraw at any time. Before you withdraw, you should talk to one of the researchers or nurses involved. This will allow them to inform you of any medical problems that could result from stopping your treatment. You can choose to withdraw one of two ways. In the first, you can stop your study treatment, but still allow the study doctor 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 to you. Your decision will not affect your medical treatment or your relationship with those treating you or with this institution. If you withdraw from the study, you will still be offered all available care that suits your needs and medical condition. You are free to seek care from a doctor of your choice at any time. Taking part in this study is voluntary. You may choose not to take part or may leave the study at any time. Leaving the study, or choosing not to take part, will not result in any penalty or loss of benefits to which you are entitled. A Data Safety and Monitoring Board, an independent group of experts, will be reviewing the data from this research throughout the study. We will tell you about the new information from this or other studies that may affect your health, welfare, or willingness to stay in this study. Additional specimen collection (not for diagnostic purposes) will not occur until you have consented for the study. 8/13/04 Page 18 of 24 Participant Initials _____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Who can answer my questions about the study? For questions about the study or a research-related injury, contact your doctor, _________________, at # _____________________. You may ask your doctor for further information on the risks, benefits or alternative treatments. For questions about your rights as a research participant, contact the ___________________ Institutional Review Board (which is a group of people at the hospital in the community where you receive treatment who review the research to protect your rights) at # ____________________ (the office of ___________________). You may also call the Operations Office of the NCI Central Institutional Review Board [CIRB] at 888-657-3711 [from the continental U.S. only]. Where can I get more information? You may call the National Cancer Institute’s (NCI’s) Cancer Information Service at: 1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615 You may also visit the NCI Web site at http://cancer.gov For the NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials For the NCI’s general information about cancer, go to: http://cancer.gov/cancerinfo Cancer Fax includes NCI information about cancer treatment, screening, prevention, and supportive care. To obtain a contents list, dial 301-402-5874 or 800-624-2511 from a fax machine hand set and follow the recorded instructions. Participant Contract I have been offered the opportunity to ask questions about this study and all questions have been answered to my satisfaction. The contents of this form have been explained to me and I understand them. I agree to allow the research personnel specified above the access to my medical records. It may be necessary for my doctor to contact me at a future date regarding new information about the treatment I received; therefore I agree to notify my doctor of any change of address and/or telephone number. My signature below means that I have voluntarily agreed to participate in this research study. I will be given a copy of all 24 pages of this consent. I may also request a copy of the study (complete study plan). 8/13/04 Page 19 of 24 Participant Initials ____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Information about thalidomide and CC-5013 has been read aloud to me in the language of my choice. I understand that if I do not follow all of my doctor’s instructions, I will not be able to receive CC-5013 or THALOMID™ (thalidomide). I now authorize my doctor to begin my treatment with CC-5013 or THALOMID™ (thalidomide). ______________ (Date) _________________________________ (Participant Signature) I have fully explained to the patient the nature, purpose, and risks of the treatment described above, especially the risks to women of childbearing potential. I have asked the patient if she/he has any questions regarding her/his treatment with CC-5013 or THALOMID™ (thalidomide) and have answered those questions to the best of my ability. I will ensure that the appropriate components of the patient consent form are completed. ______________ (Date) _________________________________ (Signature of Person Obtaining Consent) Scientific Laboratory Studies This study includes laboratory test(s) that will analyze a small sample of blood and bone marrow. These samples will be collected before you start treatment and when you discontinue the treatment on any of the treatment Groups of the trial. The blood samples will be collected using a needle to draw some blood out of a vein. The bone marrow samples, as far as possible, will be obtained at the time of the bone marrow biopsies scheduled for the treatment aspect of this study. No additional biopsies will be done to obtain this material. The blood and bone marrow will be sent to a laboratory where tests will be performed. Researchers will be performing these tests in order to understand how your treatment procedures attack your cancer cells. They hope this will help them better understand your type of cancer. The results from these tests will not be sent to you or your doctor, and will not be used in planning your care. Neither you or your insurance company will be billed for these tests. These tests are only for research purposes. Making Your Choice Please read the sentence below and think about your choice. After reading the sentence, circle "Yes" or "No." No matter what you decide to do, it will not affect your care. You can participate in the treatment part of the study without participating in the scientific laboratory studies. If you have any questions, please talk to your doctor or nurse, or call our research review board at phone # ___________________ . 8/13/04 Page 20 of 24 IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form I agree to participate in the scientific laboratory studies that are being done as a part of this study. Yes No Please print and sign your name here after you circle your answer. Your Name: Your Signature: Date:_____________ Will Any of the Samples (Blood and Bone Marrow) Taken from Me Be Used for Other Research Studies? About Using Tissue for Research If you agree to participate in the laboratory studies, samples of your blood and bone marrow will be sent to a central laboratory for tests. We would like to keep some of the blood and bone marrow that is left over for future research. If you agree, this blood and bone marrow will be kept and may be used in research to learn more about cancer and other diseases. This blood and bone marrow will only be given to researchers approved by the Eastern Cooperative Oncology Group. Any research done on the tissue must also be approved by the researcher's Institutional Review Board. The research that may be done with your blood and bone marrow will probably not help you. It might help people who have cancer and other diseases in the future. Reports about research done with your blood and bone marrow will not be given to you or your doctor. These reports will not be put in your health record. The research will not have an effect on your care. Things to Think About The choice to let us keep the left over blood and bone marrow for future research is up to you. No matter what you decide to do, it will not affect your care and you may still take part in this Eastern Cooperative Oncology Group study. If you decide now that your blood and bone marrow can be kept for research, you can change your mind at any time. Just contact your study doctor and let him or her know that you do not want us to use your blood and bone marrow. Then the blood and bone marrow will no longer be used for research. In the future, people who do research may need to know more about your health. When the Eastern Cooperative Oncology Group gives them reports about your health, it will not give them your name. 8/13/04 Page 21 of 24 IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Sometimes your blood and bone marrow is used for genetic research (about diseases that are passed on in families). Even if your blood and bone marrow is used for this kind of research, the results will not be put in your health records. Your blood and bone marrow will be used only for research and will not be sold. You will not be paid for allowing your leftover blood and bone marrow to be used in research even though the research done with your blood and bone marrow may help to develop new products in the future. Similarly there will be no cost to you for any blood and bone marrow collected and stored by the Eastern Cooperative Oncology Group. Benefits The benefits of research using your blood and bone marrow include learning more about what causes cancer and other diseases, how to prevent them, how to treat them, and how to cure them. Risks There are very few risks to you when your blood and bone marrow are stored or used in any future laboratory studies. The greatest risk is the release of information from your health records. The Eastern Cooperative Oncology Group will protect your records so that your name will be kept private. The chance that this information will be given to someone else is very small. Making Your Choice Please read each sentence below and think about your choice. After reading each sentence, circle "Yes" or "No." No matter what you decide to do, it will not affect your care. You can participate in the treatment part of the study without participating in all or part of the blood or bone marrow research studies. If you have any questions, please talk to your doctor or nurse, or call our research review board at IRB's phone number 1. My blood and bone marrow may be kept for use in research to learn about, prevent, treat, or cure cancer. Yes No 2. My blood and bone marrow may be kept for research about other health problems (for example: causes of diabetes, Alzheimer's disease, and heart disease). Yes No 3. My doctor (or someone from the Eastern Cooperative Oncology Group ) may contact me in the future to ask me to take part in more research. Yes No Please print and sign your name here after you circle your answers. Your Name: __________________________________________________________ Your Signature: _______________________________ Date: _______________ 8/13/04 Page 22 of 24 IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Study Plan Step 1 You will be randomly assigned to Groups A or B, and receive CC-5013 and dexamethasone. 1/07 If you start treatment after December of 2006, instead of Groups A or B, you will be randomly assigned to Group S or T, and receive CC-5013 and standard dose dexamethasone plus coumadin or aspirin. 1/07 Group A, S, T: You will take 25 mg/day of CC-5013 on days 1-21 of each 28-day cycle. You will also take 40 mg/day of dexamethasone, on days 1-4, 9-12 and 1720 of each cycle. Group B: You will take 25 mg/day of CC-5013 on days 1-21 of each 28-day cycle. You will also take 40 mg/day of dexamethasone, on days 1, 8, 15 and 22 of each cycle. If your myeloma gets worse while on Group A or Group B, you will have 2 options at time of progression (your treatment will be up to you and your physician): 1. register to Step 2 (Group C or D), or 2. end protocol treatment. 1/07 ● ● 1/07 3/06 3/06 1/07 1/05, 1/07 1/07 ● If your melanoma gets worse while on Group S or T, you will end protocol treatment. If your myeloma responds well to treatment at any time during the first 4 cycles of treatment on Group A,B, S, or T, you will have 2 options after the end of 4 cycles: 1. end protocol treatment and proceed to alternate therapy, such as stem cell transplant, or 2. continue protocol treatment until your myeloma shows signs of worsening (CTEP will continue to provide you with CC-5013 free of charge during this time. If your disease gets worse at any point, you will stop taking the drug and you will discuss future treatment with your doctor). If your myeloma neither responds well nor gets worse at any time during the first 4 cycles of treatment on Group A or B, you may register to Step 2 after the end of 4 cycles. Note that patients who experienced side effects while on CC-5013 which might be expected to get worse if treated with thalidomide will not register to Step 2, and will end treatment instead. If your myeloma neither responds well nor gets worse at any time during the first 4 cycles of treatment on Group S or Group T, you will end protocol treatment after 4 cycles. 8/13/04 Page 23 of 24 Participant Initials ____ IRB Approval Date __________ Version: 10/24/06; Addend. #6 Broadcast: 1/27/07 CTSU/ECOG E4A03 Southeast Cancer Control Consortium Consent Form Step 2 Patients previously on Groups A and B, who meet the requirements for Step 2 entry described above register to Groups C and D, respectively. Group C: You will take 200 mg/day of thalidomide on days 1-28 of each 28day cycle. You will also take 40 mg/day of dexamethasone, on days 1-4, 912 and 17-20 of each cycle. Group D: You will take 200 mg/day of thalidomide on days 1-28 of each 28day cycle. You will also take 40 mg/day of dexamethasone, on days 1, 8, 15 and 22 of each cycle. 1/05 If your myeloma gets worse while on Step 2 (Groups C or D), you will end protocol treatment immediately and your future treatment options will be explained by your doctor. If your myeloma responds well to treatment at any time during the first 4 cycles of Step 2 treatment have 2 options after the end of 4 cycles: 3/06 3/06 1/07 1. end protocol treatment and proceed to alternate therapy, such as stem cell transplant, or 2. continue protocol treatment until your myeloma shows signs of worsening (CTEP will continue to provide you with thalidomide free of charge during this time. If your disease gets worse at any point, you will stop taking the drug and you will discuss future treatment options with your doctor). If your myeloma neither responds well nor gets worse at any time during the first 4 cycles of treatment, you will stop receiving thalidomide after the 4 cycles are finished, and discuss future treatment options with your doctor. Southeast Cancer Control Consortium Withdrawal of Consent 8/13/04 Page 24 of 24 Participant Initials ____ CTSU/ECOG E4A03 I, _____________________________, withdraw my consent to participate in this study and refuse to be followed and have clinical data collected from my medical records. Participant Name ___________________________________ Study/ID #___________ (Please Print Name) Participant Signature ____________________________________ Date ___________ Witness Signature ______________________________________ Date ___________ Southeast Cancer Control Consortium Withdrawal of Treatment Consent 8/13/04 CTSU/ECOG E4A03 I, _____________________________, withdraw my consent for treatment on this study. Even though I withdraw my consent for treatment, I will continue to be followed and clinical data will be collected from my medical records. Participant Name ___________________________________Study/ID #____________ (Please Print Name) Participant Signature ____________________________________ Date __________ Witness Signature ______________________________________ Date __________ 8/13/04