Phase II Multicentric, Randomized Trial, Exploring Intensified Rituximab Prephase Monotherapy Before Standard Fludarabine-Cyclophosphamide-Rituximab Regimen in Previously Untreated Symptomatic B-cell Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease
研究概览
简要总结
Phase II, multicenter, randomized trial, exploring intensified Rituximab prephase monotherapy before standard Fludarabine-Cyclophosphamide-Rituximab FC-R regimen in previously untreated symptomatic B-cell chronic lymphocytic leukemia CLL.
A Study from the Goelams GCFLLCMW intergroup
详细描述
Young fit medically B Cell untreated patients Comparison between FCR treatment = 6 FCR cycles and a the addition of a prephase with R Dense treatment before the 6 FCR cycles.
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 65 Years（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
Standard R-FC arm
Standard R-FC arm 6 cycles every 28 days
-
Cycle 1:
-
Rituximab : 375 mg/m² i.v on day 1
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days For patients with Leucocyte count > 25* G/L : rituximab in two equal doses at D1, D2
-
Cycle 2-6:
-
Rituximab: 500 mg/m² i.v on day 1, repeated every 28 days
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
干预措施: Rituximab (Drug)
Standard R-FC arm
Standard R-FC arm 6 cycles every 28 days
-
Cycle 1:
-
Rituximab : 375 mg/m² i.v on day 1
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days For patients with Leucocyte count > 25* G/L : rituximab in two equal doses at D1, D2
-
Cycle 2-6:
-
Rituximab: 500 mg/m² i.v on day 1, repeated every 28 days
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
干预措施: Cyclophosphamide (Drug)
Standard R-FC arm
Standard R-FC arm 6 cycles every 28 days
-
Cycle 1:
-
Rituximab : 375 mg/m² i.v on day 1
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days For patients with Leucocyte count > 25* G/L : rituximab in two equal doses at D1, D2
-
Cycle 2-6:
-
Rituximab: 500 mg/m² i.v on day 1, repeated every 28 days
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
干预措施: Fludarabine (Drug)
DenseR-FC arm
DenseR-FC arm =1 prephase R Dense course +6 R-FC courses
- Prephase:
- Rituximab: 500 mg on day 0, 2000 mg on days 1, 8, and D15 For patients with Leucocyte count > 25* G/L : rituximab 250 mg D-1, D0 prephase
-
Cycle 1-6 (cycle 1 beginning at D22):
-
Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
干预措施: Rituximab (Drug)
DenseR-FC arm
DenseR-FC arm =1 prephase R Dense course +6 R-FC courses
- Prephase:
- Rituximab: 500 mg on day 0, 2000 mg on days 1, 8, and D15 For patients with Leucocyte count > 25* G/L : rituximab 250 mg D-1, D0 prephase
-
Cycle 1-6 (cycle 1 beginning at D22):
-
Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
干预措施: Cyclophosphamide (Drug)
DenseR-FC arm
DenseR-FC arm =1 prephase R Dense course +6 R-FC courses
- Prephase:
- Rituximab: 500 mg on day 0, 2000 mg on days 1, 8, and D15 For patients with Leucocyte count > 25* G/L : rituximab 250 mg D-1, D0 prephase
-
Cycle 1-6 (cycle 1 beginning at D22):
-
Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
-
Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
-
Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
干预措施: Fludarabine (Drug)
结局指标
主要结局
complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease
时间窗: 9 months
CR MRD negative rate at 9 months = treatment evaluation surveillance of cumulative toxicities of high dose rituximab
次要结局
- evaluate the immunophenotypic response rate after high dose Rituximab alone prephase in DenseR-FC(9 months)
- To determine the pharmacokinetics of rituximab and determine the PK-PD relationship of rituximab based on biomarkers.(12 months)
- To determine and compare the progression free survival PFS(3 years)
- To determine the event-free survival EFS(3 years)
- To evaluate the safety profile of higher doses of rituximab(41)
- To evaluate FcyRs polymorphisms influence on clinical response(9 months)
- To determine the overall survival OS(3 years)
- To determine and compare the disease-free survival DFS(3 years)
- To determine the time to next treatment TTNT(3 years)