Phase I/II Double Blind Randomized Trial of Lenalidomide/Dexamethasone/Anakinra vs. Lenalidomide/Dexamethasone/Placebo in Patients With Early Stage Multiple Myeloma and High Plasma Cell Growth Rate
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
研究概览
简要总结
This partially randomized phase I/II trial studies the side effects and best dose of anakinra when given together with lenalidomide and dexamethasone in treating patients with early stage multiple myeloma. Biological therapies, such as lenalidomide and anakinra, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether lenalidomide and dexamethasone are more effective with or without anakinra in treating patients with multiple myeloma.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD)/maximum allowable dose (MAD) of anakinra that can be combined with lenalidomide and dexamethasone. (Phase I) II. To compare the time to progression of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra). (Phase II)
SECONDARY OBJECTIVES:
I. To compare the response rate of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).
II. To compare the toxicity of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Absolute neutrophil count (ANC) >= 1700/mm^3
- •Platelet count >= 100,000/mm^3
- •Hemoglobin >= 8.0 g/dL
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x upper limit of normal (ULN)
- •Creatinine clearance >= 30 mL/min (as determined by Cockroft-Gault equation)
- •Diagnosis of multiple myeloma according to International Myeloma Working Group criteria and one of the following:
- •Smoldering multiple myeloma (SMM)
- •Indolent multiple myeloma (IMM)
- •Newly diagnosed multiple myeloma (MM)
- •Note: patients with lytic disease and anemia are eligible
- •High risk disease defined by all of the following:
- •>= 10% bone marrow plasma cells AND
- •Abnormal serum free light chain (FLC) ratio (< 0.26 or > 1.65) by serum FLC assay AND
- •Monotypic plasma cell S-phase >= 0.3%
- •Measurable level of M-protein > 1 g/dL on serum protein electrophoresis or > 200 mg of M-protein on a 24 hour urine protein electrophoresis
- •Negative tuberculosis (TB) testing (Quantiferon - TB blood test or skin test) =< 7 days prior to registration
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Provide signed informed consent
- •Negative (serum or urine) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only; NOTE: a second pregnancy test must be performed within 24 hours prior to the start of lenalidomide; the subject may not receive lenalidomide until the study doctor has verified that the results of these pregnancy tests are negative
- •Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- •Willing and able to comply with the requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
- •Females of childbearing potential must be willing to adhere to the scheduled pregnancy testing as required by the Revlimid REMS program
排除标准
- •Prior treatment with any other agent that may affect M-protein =< 30 days prior to registration
- •Acute/chronic infections, open wounds, or any active infection requiring intravenous antibiotic therapy =< 12 weeks prior to registration
- •Other active malignancy (=< 3 years) prior to registration; exceptions: basal cell skin cancer or carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •New York Heart Association (NYHA) class 3 or 4 congestive heart failure (CHF) symptoms
- •Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are allowed while on protocol treatment
研究组 & 干预措施
Arm A (lenalidomide, dexamethasone, anakinra)
Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
干预措施: Anakinra (Biological)
Arm A (lenalidomide, dexamethasone, anakinra)
Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
干预措施: Dexamethasone (Drug)
Arm A (lenalidomide, dexamethasone, anakinra)
Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (lenalidomide, dexamethasone, anakinra)
Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
干预措施: Lenalidomide (Drug)
Arm B (lenalidomide, dexamethasone, placebo)
Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Arm B (lenalidomide, dexamethasone, placebo)
Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (lenalidomide, dexamethasone, placebo)
Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Arm B (lenalidomide, dexamethasone, placebo)
Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
时间窗: 28 days
Number of participants experiencing a dose-limiting toxicity (DLT) is reported below. Dose-limiting toxicity is graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Number of Participants Who Experienced at Least One Grade 3+ Adverse Events Deemed at Least Possibly Related to Treatment, Graded According to NCI CTCAE Version 4.0
时间窗: Up to 41 months
The number of participants who experienced at least one grade 3+ adverse events deemed at least possibly related to treatment, graded according to NCI CTCAE version 4.0, is reported below.
Best Response
时间窗: Up to 41 months
The following response terms will be used: stringent Complete Response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), Minimal Response (MR), stable disease (SD), and progressive disease (PD). The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy. PR defined as: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24hrs; ≥ 50% reduction in the size of soft tissue plasmacytomas. MR defined as: ≥25% but ≤ 49% reduction of serum M protein and reduction in 24-hour urine M-protein by 50-89% which still exceeds 200mg/24 hours; 25-49% reduction in the size of soft tissue plasmacytoma and No increase in the size or number of lytic bone lesions. VGPR defined as: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein \<100 mg/24 h
次要结局
未报告次要终点