Phase III, Multicenter, Open Label, Randomized, Controlled Study Investigating Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients With Relapsed or Refractory Marginal Zone Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 260
- 试验地点
- 48
- 主要终点
- Progression-free survival (PFS) as determined by investigator
研究概览
简要总结
This is an open label, multi-center, international, randomized phase III trial to compare the efficacy of Mosunetuzumab-Lenalidomide with investigator choices exclusively in R/R MZL patients. Patients with a proven diagnosis of EMZL, SMZL or NMZL subtypes and previously treated with at least one prior systemic treatment and not more than three prior lines are eligible. Previous treatment line must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles) with or without chemotherapy (R-CHOP, R-Bendamustine, R-CVP, R-Chlorambucil at least 2 cycles) or targeted treatment such as Ibrutinib.
The patients will be Randomized as follows:
Arm A - Experimental arm:
• Mosunetuzumab-Lenalidomide
Arm B - Comparator arms ( Investigator Choices):
- Rituximab-Lenalidomide
- Rituximab-Bendamustine
- Rituximab-CHOP
详细描述
This is an open label, multi-center, international, randomized phase III trial to compare the efficacy of Mosunetuzumab-Lenalidomide with investigator choices exclusively in R/R MZL patients. Patients with a proven diagnosis of EMZL, SMZL or NMZL subtypes and previously treated with at least one prior systemic treatment and not more than three prior lines are eligible. Previous treatment line must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles) with or without chemotherapy (R-CHOP, R-Bendamustine, R-CVP, R-Chlorambucil at least 2 cycles) or targeted treatment such as Ibrutinib.
Patients are stratified according to MZL subtypes and time to progression of disease after first-line within 2 years (POD24) < 2 years or > 2 years.
Mosunetuzumab will be administered sub-cutaneously (SC) (21 days first cycle, then 28 days next cycles) and Lenalidomide will be given PO 20 mg/day from Day 1 to Day 21 from cycles C2 to C6. For each patient, investigator choice had to be decided before randomization between Rituximab-Lenalidomide and Rituximab-chemotherapy (R-Bendamustine or R-CHOP).
The primary efficacy endpoint for comparison is the Progression-free survival (PFS) as determined by investigator (Lugano criteria 2014). Secondary objectives include CR24 as determined by investigator (at 24 months) according to Lugano criteria 2014 and by central review based on PET result, Overall response rate (ORR) and CR other than CR24 as determined by investigator, or by central review based on PET result according to Lugano Criteria 2014. 260 patients are planned to be enrolled in France, Belgium, Germany, Italy and Portugal
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1: Mosunetuzumab and Lenalidomide
-
Mosunetuzumab will be administered SC (21 days first cycle, then 28 days next cycles)
-
C1 (21-days cycle): step-up dosing schedule 5 mg Day 1, 45 mg on Day 8 and 45 mg Day 15
-
C2 to C12: 45 mg D1 28-days cycles
-
Lenalidomide PO starting dose is based on patient's creatinine clearance from Day 1 to Day 21 from cycles C2 to C6 (cycles of 28 days)
干预措施: Mosunetuzumab (SC) (Drug)
Arm 1: Mosunetuzumab and Lenalidomide
-
Mosunetuzumab will be administered SC (21 days first cycle, then 28 days next cycles)
-
C1 (21-days cycle): step-up dosing schedule 5 mg Day 1, 45 mg on Day 8 and 45 mg Day 15
-
C2 to C12: 45 mg D1 28-days cycles
-
Lenalidomide PO starting dose is based on patient's creatinine clearance from Day 1 to Day 21 from cycles C2 to C6 (cycles of 28 days)
干预措施: Lenalidomide (Drug)
Arm 2: Rituximab-Lenalidomide (28-days cycles)
- Rituximab* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2-12
- Lenalidomide PO starting dose is based on patient's creatinine clearance, D1-21 from cycle 1 to cycle 6
干预措施: Rituximab (R) (Drug)
Arm 2: Rituximab-Lenalidomide (28-days cycles)
- Rituximab* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2-12
- Lenalidomide PO starting dose is based on patient's creatinine clearance, D1-21 from cycle 1 to cycle 6
干预措施: Lenalidomide (Drug)
Arm 3: Rituximab-Bendamustine (28-days cycles)
- Rituximab* 375 mg/m2 intravenously at cycle 1 Day 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2 to 6** (28-days cycles) and then at D1 of three additional 56-days cycles (C7 to C9). **For patients in complete response (CR) at 3 cycles, if Bendamustine is stopped, then Rituximab should also be omitted for C5 and C6.
- Bendamustine IV 70 or 90 mg/m² (according to the investigator's judgment) D1 and D2/28 days x 6 cycles 28 days cycles). For patients in complete response (CR) at 3 cycles, Bendamustine and Rituximab could be stopped after 4 cycles at investigator discretion
干预措施: Rituximab (R) (Drug)
Arm 3: Rituximab-Bendamustine (28-days cycles)
- Rituximab* 375 mg/m2 intravenously at cycle 1 Day 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2 to 6** (28-days cycles) and then at D1 of three additional 56-days cycles (C7 to C9). **For patients in complete response (CR) at 3 cycles, if Bendamustine is stopped, then Rituximab should also be omitted for C5 and C6.
- Bendamustine IV 70 or 90 mg/m² (according to the investigator's judgment) D1 and D2/28 days x 6 cycles 28 days cycles). For patients in complete response (CR) at 3 cycles, Bendamustine and Rituximab could be stopped after 4 cycles at investigator discretion
干预措施: Bendamustine (Drug)
Arm 4: Rituximab-CHOP (21-days cycles)
- Rituximab* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2 to 6 (21-days cycles), and then at D1 of three additional 56-days cycles (C7 to C9)
- CHOP, IV standard dose from cycle 1 to 6
干预措施: Rituximab (R) (Drug)
Arm 4: Rituximab-CHOP (21-days cycles)
- Rituximab* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2 to 6 (21-days cycles), and then at D1 of three additional 56-days cycles (C7 to C9)
- CHOP, IV standard dose from cycle 1 to 6
干预措施: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) (Drug)
结局指标
主要结局
Progression-free survival (PFS) as determined by investigator
时间窗: After 122 events = approximately 4.5 years and after 163 events = approximately 6.5 years (event = progression or death)
according to Lugano criteria 2014
次要结局
- Complete Response rate (CR) as determined by investigator (CR24)(2 years)
- Complete response rate (CR) by blinded central review (CR24)(2 years)
- Overall response rate (ORR) as determined by investigator(60 months)
- Overall response rate (ORR) by blinded central review(60 months)
- CR rate other than CR24 as determined by investigator(60 months)
- CR rate other than CR24 by blinded central review(60 months)
- Duration of response (DOR)(6.5 years)
- Event-free survival (EFS)(6.5 years)
- Time to next anti-lymphoma treatment (TTNLT)(6.5 years)
- Histological transformation rate(6.5 years)
- Safety: incidence and severity of Adverse Events (AE), of Serious Adverse Events (SAE), of Cytokine Release Syndrome (CRS), of AE grade 3 or 4 of study-drug_related events, incidence of Death and Secondary Primary Malignancies(6.5 years)
- Tolerability : number of dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events(6.5 years)
- Health related quality of life as measured by the EQ-5D-5L(24 months)