Lenalidomide, Thalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma
This trial is active, not recruiting.
|Treatments||lenalidomide, thalidomide, dexamethasone|
|Phase||phase 1/phase 2|
|Sponsor||M.D. Anderson Cancer Center|
|Start date||August 2009|
|End date||August 2017|
|Trial size||64 participants|
|Trial identifier||NCT00966693, 2009-0179, NCI-2009-01622|
The goal of the Phase I portion of this clinical research study is to find the highest tolerated dose of the combination of thalidomide, lenalidomide, and dexamethasone that can be given to patients with relapsed or refractory MM.
The goal of the Phase II portion of this study is to learn if the drug combination can help to control the disease.
The safety of the drug combination will be studied in both phases.
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Maximum Tolerated Dose (MTD) of Combination of Lenalidomide, Thalidomide and Dexamethasone in Multiple Myeloma Participants
time frame: End of Cycle 1 (28 Days)
Male or female participants at least 18 years old.
Inclusion Criteria: 1. Understand and voluntarily sign an informed consent form. 2. Age >/= 18 years at the time of signing the informed consent form. 3. Relapsed/refractory MMM with measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or abnormal free light chain (FLC) ratio. 4. Serum Creatinine = 2.5 mg/dl 5. Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional affective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. 6. Continuation from Inclusion # 6: FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. 7. Continuation from Inclusion # 7: * A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). 8. Laboratory test results within these ranges: Absolute neutrophil count > 1000 cells/mm^3 Platelet count > 50,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells and platelet count > 25,000 cells/mm^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells Total bilirubin = 2.0 mg/dL AST (SGOT) and ALT (AGPT) < 3 x ULN 9. Able to take prophylactic anticoagulation, warfarin or equivalent agent 10. Patient is able to understand and comply with the terms and conditions of the Lenalidomide and Thalidomide Counseling Program 11. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®, AND the S.T.E.P.S.® program. Exclusion Criteria: 1. Any serious medical condition, or psychiatric illness that would prevent the subject from signing the informed consent form 2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide). 3. Use of any cancer therapy within 21 days prior to beginning cycle 1 day 1 of therapy (radiation therapy allowed within 5 days of completion of radiation therapy). 4. Known hypersensitivity to thalidomide, lenalidomide and dexamethasone. 5. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
|Official title||Phase I/II Study of Lenalidomide (Revlimid), Thalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma|
|Description||The Study Drugs: Lenalidomide and thalidomide are drugs that alter the immune system and that may also interfere with the development of blood vessels that help support tumor growth. This may reduce or prevent the growth of cancer cells. Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body. Dexamethasone is often given to MM patients in combination with other chemotherapy to treat cancer. Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 4 groups of up to 3-6 patients participants will be enrolled in the Phase I portion of the study, and up to 46 participants will be enrolled in Phase II. If you are enrolled in the Phase I portion, the dose of lenalidomide and thalidomide you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of the combination. Each new group will receive a higher dose of the combination than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of lenalidomide and thalidomide is found. If you are enrolled in the Phase II portion, you will receive the combination of lenalidomide and thalidomide at the highest dose that was tolerated in the Phase I portion. All participants will receive the same dose level of dexamethasone. Study Drug Administration: Each study cycle is 28 days. On Days 1-21 of Cycles 1-8, you will take lenalidomide by mouth at the same time every day, You should take it with a glass of water on either a full or an empty stomach. Do not break, chew, or open the capsules. If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose). On Days 1-28 of Cycles 1-8, you will take thalidomide by mouth. You should take thalidomide in the evenings with a full glass (about 8 ounces) of water. On Days 1-4, 9-12, and 17-20 of Cycles 1-2, you will take dexamethasone by mouth with meals one time each day . On Days 1, 8, 15, and 22 of Cycles 3-8, you will take dexamethasone by mouth one time each day. You will be given a diary to record when you take all of the study drugs and any problems or illnesses you experience. You should also write down in the diary any other drugs you take while you are on the study. You should bring this diary with you to each visit. Maintenance Therapy Study Drug Administration: If you are in Phase 1 or 2, after completing 8 cycles, if you have stable or responding disease to study drugs and you have not experienced intolerable side effects, you will be able to continue taking the study drugs on a maintenance schedule. You will stay on this schedule for as long as you are benefitting. - On Days 1-21 of each cycle of maintenance therapy, you will take lenalidomide by mouth. - On Days 1-28 of each cycle of maintenance therapy, you will take thalidomide by mouth. - If your doctor feels that it is needed, you may continue taking dexamethasone during the maintenance period. The dose level of lenalidomide will be the same dose you took during Cycle 8. The dose level of thalidomide will be the lowest dose during the study (which may be a lower dose then you were receiving during Cycles 1-8) If the doctor thinks it is needed, the doses may also be lowered depending on how well you are tolerating the drugs. Study Visits: On Days 1, 8, 15, and 22 of Cycle 1, the following tests and procedures will be performed: - You will have a physical exam, including measurement of your vital signs and weight. - Your performance status will be recorded. - Blood (about 1 tablespoon) will be drawn for routine tests. - You will be asked questions about how you are feeling. On about Day 1 of Cycles 2-8, the following tests and procedures will be performed: - You will have a physical exam. - You will be asked to list any drugs you have taken and about how you have felt since your last visit. - Blood (about 3 tablespoons) will be drawn for routine blood tests. - Urine will be collected to check the status of the disease. This urine will be collected over a 24-hour period, you will be provided with a container for urine collection. - You will have a neurologic exam. - You will have an ECG. - You will complete the questionnaire about symptoms - Blood (about 1 teaspoon) will be drawn to measure proteins in your blood. - Blood (about 1 teaspoon) will be drawn to measure cytokine levels every even cycle (Cycles 2, 4, 6 and so on). - If the disease completely responds to the drugs, you will have a bone marrow biopsy to confirm complete response. To collect a bone marrow biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. - If the doctor thinks it is needed, you will have x-rays of your bones to check the status of the bone lesions. - If the doctor thinks it is needed, you will have MRI scans of your bones to check on the number of bone lesions. If your doctor feels it is needed, the visits may take place more often. You may have extra visits at any time during the study if your doctor feels it is needed for your care. Maintenance Therapy Study Visits: Once a month during Maintenance Therapy, the following tests and procedures will be performed: - Blood (about 2 teaspoons) will be drawn for routine tests. - Blood (about 1 teaspoon) will be drawn to measure proteins in your blood. - Urine will be collected to check the status of the disease. This urine will be collected over a 24-hour period, you will be provided with a container for urine collection. - If the disease completely responds to the drugs, you will have a bone marrow biopsy to confirm complete response. Length of Study: You will receive up to 8 cycles of the study drugs. If the doctor thinks it is in your best interest, you will continue to receive the study drugs as Maintenance Therapy for as long as you are benefitting. You will be taken off study if the disease gets worse or you experience intolerable side effects. End-of-Study Visit: If you go off study for any reason, you will have an end-of-study visit. This is usually done about 30 days after the last dose of the study drugs. At this visit, the following tests and procedures will be performed: - You will have a physical exam, including measurement of your vital signs and weight. - Blood (about 2-3 teaspoons) and urine (over 24 hours) will be collected to check the status of the disease. - Blood (about 1 tablespoon) will be drawn for routine tests. - Urine will be collected to check the status of the disease. This urine will be collected over a 24-hour period, you will be provided with a container for urine collection. - If the disease completely responds to the drugs, you will have a bone marrow biopsy to confirm complete response. This is an investigational study. Lenalidomide is FDA approved and commercially available for the treatment of types of myelodysplastic syndrome (MDS). Dexamethasone is FDA approved and commercially available for use in combination with lenalidomide for the treatment of patients with MM who have received at least 1 prior therapy. Thalidomide is FDA approved and commercially available for the treatment of newly diagnosed myeloma. The use of this drug combination when given to patients with relapsed or refractory MM is investigational. Up to 64 patients will take part in this clinical research study. All will be enrolled at MD Anderson.|
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