A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (BMT CTN 0702)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 758
- 试验地点
- 54
- 主要终点
- Percentage of Participants With Progression-free Survival (PFS)
研究概览
简要总结
The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus maintenance therapy versus the strategy of single autologous transplant plus consolidation therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy or single autologous transplant plus maintenance therapy as part of upfront treatment of multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in all arms.
详细描述
The primary objective of the randomized trial is to compare three-year progression-free survival (PFS) between the three treatment arms as a pairwise comparison. Mobilization therapy will not be specified for the study. Randomization to three treatment arms will be done prior to the first transplants. All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive either a second autologous PBSC transplant with the same conditioning regimen as the first transplant or consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40 mg on Days 1, 8 and 15, and bortezomib 1.3mg/m^2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles) or maintenance with lenalidomide (15 mg daily). All patients will also receive maintenance lenalidomide which will start after the second transplant, after the first autologous transplant or after consolidation therapy depending on the treatment arm. Maintenance therapy with lenalidomide will start at 10 mg daily for three months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
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
- None
入排标准
- 年龄范围
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients meeting the criteria for symptomatic multiple myeloma (MM).
- •Patients who are 70 years of age, or younger, at time of enrollment.
- •Patients who have received at least two cycles of any regimen as initial systemic therapy and are within 2 - 12 months of the first dose of initial therapy.
- •Cardiac function: left ventricular ejection fraction at rest greater than 40 percent.
- •Hepatic: bilirubin less than 1.5x the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 2.5x the upper limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of 1.5x the upper limit of normal.)
- •Renal: Creatinine clearance of grater than or equal to 40 mL/min, estimated or calculated.
- •Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater than 50 percent of predicted value (corrected for hemoglobin).
- •Patients with an adequate autologous graft defined as a cryopreserved PBSC graft containing greater than or equal to 4 x 10^6 CD34+ cells/kg patient weight. The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center. The autograft must be stored so that there are two products each containing at least 2 x 10^6 CD34+ cells/kg patient weight.
- •Signed informed consent form.
排除标准
- •Patients who never fulfill the criteria for symptomatic MM.
- •Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques]. Patients with light chain MM detected in the serum by free light chain assay are eligible.
- •Patients with plasma cell leukemia.
- •Karnofsky performance score less than 70 percent.
- •Patients with greater than grade 2 sensory neuropathy (CTCAE).
- •Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).
- •Patients seropositive for the human immunodeficiency virus (HIV).
- •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- •Patient has hypersensitivity to bortezomib, boron or mannitol.
- •Patient has received other investigational drugs with 14 days before enrollment.
- •Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent greater than 5 years previously is allowed.
- •Female patients who are pregnant (positive B-HCG) or breastfeeding.
- •Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques during the length of lenalidomide maintenance therapy.
- •Prior allograft or prior autograft.
- •Patients who have received mid-intensity melphalan (greater than 50 mg IV) as part of prior therapy.
- •Patients unable or unwilling to provide informed consent.
- •Prior organ transplant requiring immunosuppressive therapy.
- •Patients with disease progression prior to enrollment.
- •Patients who have received lenalidomide as initial therapy for MM and have experienced toxicities resulting in treatment discontinuation.
- •Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.
- •Patients unwilling to take deep vein thrombosis (DVT) prophylaxis.
- •Patients who cannot undergo an intervention in any treatment arm due to a priori denial of medical costs coverage by third party payers.
- •Patients unable to unwilling to return to the transplant center for their assigned treatments.
研究组 & 干预措施
Tandem auto transplant
Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance
干预措施: Lenalidomide (Drug)
RVD consolidation
Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance
干预措施: lenalidomide, bortezomib and dexamethasone (Drug)
Lenalidomide maintenance
Initial autologous transplant followed by lenalidomide maintenance
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Percentage of Participants With Progression-free Survival (PFS)
时间窗: 38 months post-randomization
Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate progression-free survival at 38 months post-randomization.
次要结局
- Percentage of Participants With Disease Progression(38 months post-randomization)
- Number of Participants With Treatment Response(1 and 2 years post-randomization)
- Percentage of Participants With Overall Survival (OS)(38 months post-randomization)
- FACT-BMT Score(Up to 3 years post-randomization)
- Percentage of Participants With Treatment-related Mortality (TRM)(Up to 38 months post-randomization)
- MOS SF-36 Physical Component Summary(Up to 3 years post-randomization)
- MOS SF-36 Mental Component Summary(Up to 3 years post-randomization)
- FACT-G Total Score(Up to 3 years post-randomization)
- FACT-BMT Trial Outcome Index(Up to 3 years post-randomization)