Phase III Trial of Combined Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) Versus Bendamustine and Rituximab (BR) in Patients With Previously Untreated Chronic Lymphocytic Leukaemia
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- German CLL Study Group
- Enrollment
- 564
- Locations
- 1
- Primary Endpoint
- Progression-free survival rate after 24 months
Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving fludarabine and cyclophosphamide together with rituximab is more effective than giving bendamustine together with rituximab in treating chronic lymphocytic leukemia.
PURPOSE: This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared with bendamustine and rituximab in treating patients with previously untreated B-cell chronic lymphocytic leukemia.
Detailed Description
OBJECTIVES:
- To compare the therapeutic efficacy of fludarabine phosphate, cyclophosphamide, and rituximab vs bendamustine hydrochloride and rituximab in patients with previously untreated B-cell chronic lymphocytic leukemia.
- To compare the incidence of major side effects (e.g., myelosuppression) associated with these regimens in these patients.
- To compare the rate of infections and secondary neoplasias in patients treated with these regimens.
OUTLINE: This is a multicenter study. Patients are stratified according to country and disease stage. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive fludarabine phosphate IV and cyclophosphamide IV on days 1-3. Patients also receive rituximab IV on day 0 of course 1 and on day 1 of courses 2-6. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive bendamustine hydrochloride IV on days 1 and 2. Patients also receive rituximab as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients complete quality of life questionnaires (EORTC-C30 and EURO-QOL) at baseline and then at 12, 24, 36, 48, and 60 months.
After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year thereafter.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
FCR
Intervention: Rituximab (Biological)
FCR
Intervention: Cyclophosphamide (Drug)
FCR
Intervention: Fludarabine (Drug)
BR
Intervention: Rituximab (Biological)
BR
Intervention: Bendamustine (Drug)
Outcomes
Primary Outcomes
Progression-free survival rate after 24 months
Time Frame: 2008-2015
estimated time point when 198 needed events for the final analysis(PD or deaths) have occured.
Secondary Outcomes
- Quality of life(2008-2015)
- Event-free survival(2008-2015)
- Minimal residual disease, complete response rates, and partial response rates(2008-2015)
- Duration of remission(2008-2015)
- Overall response rate(2008-2015)
- Response rates in and survival times in biological subgroups(2008-2015)
- Overall survival(2008-2015)
- Toxicity rates(2008-2015)
- Standard safety analysis(2008-2015)