Fludarabine, Cyclophosphamide, and Rituximab Followed by Rituximab or Observation in Treating Older Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia (LLC2007SA)
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, 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 rituximab alone after chemotherapy and rituximab is more effective than chemotherapy and rituximab followed by observation in treating chronic lymphocytic leukemia.
PURPOSE: This randomized phase III trial is studying giving fludarabine together with cyclophosphamide and rituximab followed by rituximab alone to see how well it works compared with giving fludarabine together with cyclophosphamide and rituximab followed by observation in treating older patients with previously untreated B-cell chronic lymphocytic leukemia.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Single-agent Rituximab as Maintenance Treatment Versus Observation After Combined Induction Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) in Patients Older Than 65 Years With Previously Untreated B-cell Chronic Lymphocytic Leukemia (B-CLL): a Phase III Intergroup Trial of the GOELAMS and the FCGCLL/WM Groups|
- Three-year progression-free survival [ Time Frame: from randomisation to progression or relapse ] [ Designated as safety issue: Yes ]induction treatment + at 36 months from randomisation
- Event-free survival [ Time Frame: from randomisation to first event ] [ Designated as safety issue: Yes ]
- Disease-free survival [ Time Frame: from first documented CR to relapse ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: From randomisation to death from any cause ] [ Designated as safety issue: Yes ]
- Time to next treatment [ Time Frame: From randomisation to initiation of a new disease-related treatment ] [ Designated as safety issue: Yes ]
- Overall response rate, complete response, and partial response according to NCI criteria [ Time Frame: response post induction and response at 36 months from randomisation ] [ Designated as safety issue: Yes ]
- Rates of phenotypic response (minimal residual disease) [ Time Frame: response post induction and response at 36 months from randomisation ] [ Designated as safety issue: Yes ]
- Rates of treatment-related adverse events [ Time Frame: all over the study duration ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of rituximab during induction and maintenance [ Time Frame: during induction and maintenance treatment ] [ Designated as safety issue: Yes ]
- Quality of life [ Time Frame: post induction and during maintenance phase ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2007|
|Estimated Study Completion Date:||August 2019|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
No Intervention: Observation
Observation every 8 months during 2 years
Experimental: rituximab arm
rituximab :500 mg/m² every 8 weeks every 2 years
rituximab :500 mg/m² every 8 weeks every 2 years
Other Name: Mabthera
- To demonstrate superiority, in terms of 3-year progression-free survival (PFS), of rituximab maintenance over observation in patients who are in complete or partial response (CR or PR) after induction therapy comprising fludarabine phosphate, cyclophosphamide, and rituximab.
- To determine event-free survival, disease-free survival, overall survival, and time to next treatment, all from time of randomization.
- To determine overall response rate (CR and PR) according to NCI criteria.
- To assess the rate of phenotypic response (minimal residual disease).
- To assess duration of phenotypic and NCI clinical responses.
- To determine response rates and time-related parameters in biological subgroups.
- To determine rates of treatment-related adverse events.
- To evaluate of CD4/CD8 counts, immunoglobulin levels, and incidence of Coombs-positive hemolytic anemia.
- To study pharmacokinetics of rituximab during induction and maintenance.
- To evaluate the prognostic impact of the immunoglobulin FcγRIIIA genotype.
- To assess quality of life.
- To study pharmacoeconomics.
OUTLINE: This is a multicenter study. Patients are stratified according to response to induction therapy (complete response [CR] vs partial response [PR]), IgV_H mutational status, and 11q deletion.
Patients receive rituximab IV on days 1 and 14 of courses 1-2 and on day 1 of courses 3 and 4. Patients also receive oral fludarabine phosphate and oral cyclophosphamide once daily on days 2-4 of course 1 and on days 1-3 of courses 2-4. Courses repeat every 28 days. Patients achieving CR or PR are randomized to 1 of 2 maintenance arms once they have recovered from toxicities.
- Arm A: Patients receive rituximab IV on day 1. Treatment repeats every 2 months in the absence of disease progression for a maximum duration of 24 months (12 infusions).
- Arm B: Patients undergo observation only. Patients undergo lymphocyte sample collection for biological studies including diagnostic immunophenotyping, Matutes score (with CD38, CD20, and CD43) , ZAP-70 analysis, standard karyotyping, cytogenetic screening by FISH (17p13 deletion, 11q22 deletion, 13q14 deletion, and trisomy 12), IgV_H mutational status, serum thymidine kinase, FcγRIIIA genotyping, and pharmacokinetic study. Samples are frozen and stored for later studies.
After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for up to 4 years.
|Contact: Caroline DARTIGEAS, MDfirstname.lastname@example.org|
|Contact: Roselyne DELEPINE, Mrsemail@example.com|
|Groupe Ouest Est d'etude des Leucemies et Autres Maladies du Sang||Recruiting|
|TOURS Cedex, France, 37044|
|Contact: Stephanie ROY, Mrs 33-2-4739-1896 firstname.lastname@example.org|
|Principal Investigator:||Caroline Dartigeas, MD||Centre Hospitalier Universitaire Bretonneau de Tours|
|Principal Investigator:||Eric VAN DEN NESTE, MD PhD||FCGCLL/MW|