A Phase 3B Randomized Study of Lenalidomide (CC-5013) Plus Rituximab Maintenance Therapy Followed by Lenalidomide Single-Agent Maintenance Versus Rituximab Maintenance in Subjects With Relapsed/Refractory Follicular, Marginal Zone, or Mantle Cell Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 503
- 试验地点
- 126
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
Follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) are distinct histologic types of B-cell NHL. Lenalidomide is an immunomodulatory agent with direct and immune-mediated mechanisms of action, as well as clinical activity in NHL. Recent studies in frontline and relapsed/refractory NHL show high activity for lenalidomide plus rituximab (R2), supporting further study of this combination.
详细描述
MAGNIFY (NCT01996865) is a phase 3b, multicenter, open-label study of patients with grades 1-3b or transformed follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) who received ≥1 prior therapy and had stage I-IV, measurable disease. ~500 patients are planned for enrollment in 12 cycles of R2 induction, with a projected ~314 patients with ≥SD after induction randomized (1:1) to two maintenance arms. Induction includes oral lenalidomide 20 mg/day, days 1-21 per 28-day cycle (d1-21/28) plus IV rituximab 375 mg/m2, days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 3, 5, 7, 9, and 11 (28-day cycles). Patients are then randomized to maintenance lenalidomide 10 mg/day, d1-21/28, cycles 13-30, plus rituximab 375 mg/m2, day 1 of cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29 (R2, Arm A), or rituximab alone (same schedule, Arm B). Patients receiving R2 maintenance after 18 cycles may continue maintenance lenalidomide monotherapy 10 mg/day, d1-21/28 (per patient and/or investigator discretion), until disease progression as tolerated. The primary endpoint is progression-free survival (per modified 1999 IWG criteria). Secondary endpoints include safety, overall survival, response rates, duration of response, and quality of life (exploratory). Patients will be followed for ≥5 years after the last patient initiated induction therapy. Enrollment in MAGNIFY began in March 2014; as of Jan 2016, 133 patients are enrolled.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Age ≥18 years
- •Histologically confirmed Follicular Lymphoma (FL, Grade 1, 2, 3a, or 3b), Transformed FL, Marginal Zone Lymphoma, or Mantle Cell Lymphoma
- •Must have documented relapsed, refractory or Progressive Disease after last treatment with systemic therapy
- •Bi-dimensionally measurable disease
- •Eastern Cooperative Oncology Group (ECOG) Performance status < 2
- •Adequate bone marrow function
- •Willingness to follow pregnancy precautions
排除标准
- •Histology other than follicular or marginal zone lymphoma or clinical evidence of transformation or Grade 3b follicular lymphoma
- •Any medical condition (other than the underlying lymphoma) that requires chronic steroid use
- •Subjects taking corticosteroids during the last 1 week prior treatment, unless administered at a dose equivalent to < 20 mg/day of prednisone
- •Systemic anti-lymphoma therapy within 28 days or use of antibody agents within 4 weeks use of radioimmunotherapy within 3 months
- •Known seropositive for or active viral infection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)
- •Known sensitivity or allergy to murine products
- •Presence or history of central nervous system involvement by lymphoma. Subjects who are at a risk for a thromboembolic event and are not willing to take prophylaxis for it
- •Any condition that places the subject at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Arm A: Lenalidomide + rituximab followed by lenalidomide
Induction Period (12 cycles): Lenalidomide 20mg (10 mg if creatinine clearance ≥ 30 mL/min but < 60mL/min) by mouth (PO) daily (QD) on Days 1 to 21 of every 28-day cycle during cycles 1 through 12 and rituximab 375mg/m^2 intraveneously (IV) every week in Cycle 1 on Days 1, 8, 15, and 22 and on Day 1 of every 28-day cycle during cycles 3, 5, 7, 9, and 11, followed by a Maintenance Period (lasting 18 Cycles) that includes Lenalidomide 10 mg PO QD on Days 1 to 21 of every 28-day cycle during cycles 13 to 30 and rituximab 375 mg/m^2 IV on Day 1 of every 28-day cycle during cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29 followed by an optional Maintenance Period (up to Progressive Disease) receiving Lenalidomide 10mg PO QD on Days 1 through 21 of every 28 day cycle until the disease progresses
干预措施: Lenalidomide (Drug)
Arm A: Lenalidomide + rituximab followed by lenalidomide
Induction Period (12 cycles): Lenalidomide 20mg (10 mg if creatinine clearance ≥ 30 mL/min but < 60mL/min) by mouth (PO) daily (QD) on Days 1 to 21 of every 28-day cycle during cycles 1 through 12 and rituximab 375mg/m^2 intraveneously (IV) every week in Cycle 1 on Days 1, 8, 15, and 22 and on Day 1 of every 28-day cycle during cycles 3, 5, 7, 9, and 11, followed by a Maintenance Period (lasting 18 Cycles) that includes Lenalidomide 10 mg PO QD on Days 1 to 21 of every 28-day cycle during cycles 13 to 30 and rituximab 375 mg/m^2 IV on Day 1 of every 28-day cycle during cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29 followed by an optional Maintenance Period (up to Progressive Disease) receiving Lenalidomide 10mg PO QD on Days 1 through 21 of every 28 day cycle until the disease progresses
干预措施: Rituximab (Drug)
Arm B: Lenalidomide + rituximab followed by rituximab
Induction Period (12 Cycles): Lenalidomide 20 mg PO QD (10 mg if creatinine clearance ≥ 30 mL/min but < 60 mL/min) on Days 1 to 21 of every 28-day cycle during cycles 1 to 12 and rituximab 375 mg/m^2 IV every week in cycle 1 on Days 1, 8, 15, and 22 and on Day 1 of every 28-day cycle during cycles 3, 5, 7, 9, and 11, followed by a Maintenance Period for 18 Cycles that includes: Rituximab 375 mg/m^2 IV on Day 1 of every 28-day cycle during cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
干预措施: Lenalidomide (Drug)
Arm B: Lenalidomide + rituximab followed by rituximab
Induction Period (12 Cycles): Lenalidomide 20 mg PO QD (10 mg if creatinine clearance ≥ 30 mL/min but < 60 mL/min) on Days 1 to 21 of every 28-day cycle during cycles 1 to 12 and rituximab 375 mg/m^2 IV every week in cycle 1 on Days 1, 8, 15, and 22 and on Day 1 of every 28-day cycle during cycles 3, 5, 7, 9, and 11, followed by a Maintenance Period for 18 Cycles that includes: Rituximab 375 mg/m^2 IV on Day 1 of every 28-day cycle during cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
干预措施: Rituximab (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From the first dose date of maintenance therapy to objective disease progression or death from any cause, whichever occurs first (up to approximately 432 weeks)
Progression free survival (PFS) is defined as the time from the date of first dose of maintenance therapy to the date of the first objective documentation of tumor progression or death due to any cause. Analysis was based on Kaplan Meier estimates. The PFS events were determined using a modification of the IWG 1999 criteria.
次要结局
- Overall Survival (OS)(From the first dose date of maintenance therapy to death from any cause (up to approximately 480 weeks))
- Improvement of Response (IOR)(From the first dose date of maintenance therapy to death from any cause (up to approximately 432 weeks))
- Overall Response Rate (ORR)(From the first dose date of maintenance therapy up to CR, CRu, PR, or treatment change (up to approximately 432 weeks))
- Complete Response Rate (CRR)(From the first dose date of maintenance therapy up to CR or CRu (up to approximately 432 weeks))
- Duration of Response (DOR)(From the initial response (at least PR) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks))
- Time to Next Anti-lymphoma Treatment(From the first dose date of maintenance therapy to the time of first documented administration of new anti-lymphoma therapy (up to approximately 300 weeks))
- Time to Histological Transformation(From the first dose date of maintenance therapy to the time of histological transformation (up to approximately 432 weeks))
- Duration of Complete Response (DOCR)(From the initial CR/CRu after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks))
- Participants Experiencing Treatment Emergent Adverse Events (TEAEs)(From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period))
- Participants Experiencing Adverse Events Related to Vital Signs(From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period))
- Participants With Grade 3 or Grade 4 Hematology Parameters(From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period))
- Participants With Grade 3 or Grade 4 Serum Chemistry Parameters(From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period))