Phase I/II Study of Lenalidomide (Revlimid), All-trans Retinoic Acid (ATRA) and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Lenalidomide/Dexamethasone and All-Trans Retinoic Acid (ATRA)
研究概览
简要总结
The goal of the Phase I portion of this clinical research study is to find the highest tolerated dose of the combination of lenalidomide, all-trans retinoic acid (ATRA), and dexamethasone that can be given to patients with relapsed or refractory multiple myeloma (MM).
The goal of the Phase II portion of this study is to learn if ATRA when given in combination with lenalidomide alone or with lenalidomide and dexamethasone can help to control multiple myeloma.
In September 2015, the study was terminated due to slow accrual while still a Phase I study, no additional registration or research performed under the Phase II portion of the study.
详细描述
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 2 groups of up to 3-6 patients participants will be enrolled in the Phase I portion of the study, and up to 58 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of lenalidomide, dexamethasone, and ATRA 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 ATRA is found.
If you are enrolled in the Phase II portion, you will be assigned to 1 of 2 groups based on the therapy you were receiving before you began to take part in this study.
- If you were receiving lenalidomide alone, you will take lenalidomide and ATRA (Group A).
- If you were receiving lenalidomide and dexamethasone when you started this study, you will take lenalidomide, dexamethasone, and ATRA (Group B).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Understand and voluntarily sign an informed consent form
- •Age >/= 18 years at the time of signing the informed consent form
- •Serum creatinine </= 2.5 mg/dl OR Creatine clearance > 30 ml/min
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- •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. 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.
- •Continuation from Inclusion #5: *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).
- •Able to take prophylactic antiplatelet/anticoagulation, warfarin or equivalent agent
- •Patient is able to understand and comply with the terms and conditions of the Lenalidomide Counseling Program.
- •Phase I Specific Inclusion Criteria: Multiple myeloma that has progressed on lenalidomide and dexamethasone combination therapy at a dose of 25 mg daily on lenalidomide and 40 mg weekly of dexamethasone 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.
- •Phase I Specific Inclusion Criteria: Laboratory test results within these ranges: Absolute neutrophil count > 1000 cells/mm^3; Platelet count > 100,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells and platelet count > 50,000 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 upper limits of normal (ULN)
- •Phase II Specific Inclusion Criteria: Cohort A: Multiple myeloma that has progressed on lenalidomide and dexamethasone combination therapy with measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or involved FLC level by more than 10 mg/dL and abnormal free light chain (FLC) ratio. Cohort B: Multiple myeloma that has progressed on single agent lenalidomide therapy with measurable disease defined as: doubling of the M-component in 2 consecutive measurements in less than or equal to 2 months OR increase in serum M-protein levels by >/= .5g or urine protein by 200mg/24 hours, or involved FLC level by more than 10 mg/dL (with an abnormal FLC ratio).
- •Phase II Specific Inclusion Criteria: Laboratory test results within these ranges: Absolute neutrophil count > 1000 cells/mm^3; Platelet count > 75,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells and platelet count > 50,000 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
排除标准
- •Any serious medical condition, or psychiatric illness that would prevent the subject from signing the informed consent form.
- •Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- •Use of any cancer therapy within 14 days prior to beginning cycle 1 day 1 of therapy with the exception of lenalidomide and dexamethasone (radiation therapy allowed within 5 days of completion of radiation therapy)
- •Known hypersensitivity to lenalidomide or ATRA.
研究组 & 干预措施
Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA)
Phase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21. Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22. ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21.
Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment. Dexamethasone starting dose: Dose previously on when progressing prior to study entry. ATRA starting dose: MTD from Phase I.
Maintenance Therapy Group A: Lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days, with ATRA at dose determined in Phase I for 14/28 days, and Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22. After 3 months on therapy at MTD in Phase I study, patients must be switched to this dose schedule. Patients unable to tolerate either Dexamethasone during maintenance phase may dose reduce Dexamethasone as needed.
干预措施: Lenalidomide (Drug)
Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA)
Phase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21. Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22. ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21.
Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment. Dexamethasone starting dose: Dose previously on when progressing prior to study entry. ATRA starting dose: MTD from Phase I.
Maintenance Therapy Group A: Lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days, with ATRA at dose determined in Phase I for 14/28 days, and Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22. After 3 months on therapy at MTD in Phase I study, patients must be switched to this dose schedule. Patients unable to tolerate either Dexamethasone during maintenance phase may dose reduce Dexamethasone as needed.
干预措施: Dexamethasone (Drug)
Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA)
Phase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21. Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22. ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21.
Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment. Dexamethasone starting dose: Dose previously on when progressing prior to study entry. ATRA starting dose: MTD from Phase I.
Maintenance Therapy Group A: Lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days, with ATRA at dose determined in Phase I for 14/28 days, and Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22. After 3 months on therapy at MTD in Phase I study, patients must be switched to this dose schedule. Patients unable to tolerate either Dexamethasone during maintenance phase may dose reduce Dexamethasone as needed.
干预措施: All-Trans Retinoic Acid (ATRA) (Drug)
Lenalidomide + All-Trans Retinoic Acid (ATRA)
Phase II Group B: Lenalidomide will be given as a single oral dose at the level patient was on at the time of progression on single agent Lenalidomide prior to study enrollment. All-Trans Retinoic Acid (ATRA) starting dose: MTD from Phase I.
Maintenance Therapy: Maintenance therapy consists of lenalidomide at the dose level tolerated at the completion of cycle 3 for 21/28 days, with ATRA at the dose determined in the phase I portion of the trial for 14/28 days. Dexamethasone will not be administered. After 3 months on therapy at the MTD in the phase 1 study, patients must be switched to this dose schedule.
干预措施: Lenalidomide (Drug)
Lenalidomide + All-Trans Retinoic Acid (ATRA)
Phase II Group B: Lenalidomide will be given as a single oral dose at the level patient was on at the time of progression on single agent Lenalidomide prior to study enrollment. All-Trans Retinoic Acid (ATRA) starting dose: MTD from Phase I.
Maintenance Therapy: Maintenance therapy consists of lenalidomide at the dose level tolerated at the completion of cycle 3 for 21/28 days, with ATRA at the dose determined in the phase I portion of the trial for 14/28 days. Dexamethasone will not be administered. After 3 months on therapy at the MTD in the phase 1 study, patients must be switched to this dose schedule.
干预措施: All-Trans Retinoic Acid (ATRA) (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Lenalidomide/Dexamethasone and All-Trans Retinoic Acid (ATRA)
时间窗: 28 days
MTD defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose limiting toxicity refers to a medically significant event which meets one of the following: Hematologic dose-limiting toxicity defined as either, Grade 4 neutropenia lasting for \>/=14 days in duration ( growth factors permitted after DLT established), Grade 4 thrombocytopenia \> 14 days despite platelet transfusions. Non-hematologic DLT defined as any Grade 3, 4 or 5 non-hematologic toxicity, with the specific exception of, Isolated Grade 3 elevation of liver function tests (LFTs) without associated clinical symptoms, lasting for \</=7 days in duration, Isolated Grade 3 elevation of amylase without associated clinical symptoms, Grade 3 hypocalcemia, hyperglycemia, hypokalemia, hypomagnesemia, hyponatremia, or hypophosphatemia which responds to medical intervention.
次要结局
- Objective Response(After 4, 28 day cycles)