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
Overview
- Phase
- Phase 2
- Intervention
- Rituximab
- Conditions
- B-cell Chronic Lymphocytic Leukemia CLL
- Sponsor
- French Innovative Leukemia Organisation
- Enrollment
- 140
- Locations
- 2
- Primary Endpoint
- complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
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
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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
Intervention: Rituximab
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
Intervention: Cyclophosphamide
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
Intervention: Fludarabine
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
Intervention: Rituximab
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
Intervention: Cyclophosphamide
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
Intervention: Fludarabine
Outcomes
Primary Outcomes
complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease
Time Frame: 9 months
CR MRD negative rate at 9 months = treatment evaluation surveillance of cumulative toxicities of high dose rituximab
Secondary Outcomes
- 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)