Randomized Phase III Trial Comparing Early Treatment With Fludarabine/Cyclophosphamide + Rituximab Versus Deferred Treatment in Untreated Binet Stage A Patients With CLL and High Risk of Progression
- Compare the effect, in terms of event-free survival, of deferred versus immediate
treatment with rituximab, fludarabine, and cyclophosphamide in patients with previously
untreated Binet stage A chronic lymphocytic leukemia at high risk for disease
- Investigate and define a new prognostic staging system for patients with Binet stage A
chronic lymphocytic leukemia.
- Compare the time to progression to Binet stages B and C in patients treated with these
- Compare the overall and progression-free survival of patients treated with these
- Compare the quality of life of patients treated with these regimens.
- Compare the time to treatment in patients treated with these regimens.
- Analyze the pharmacoeconomics of these regimens in these patients.
- Determine the overall response rate (partial and complete) in patients included in the
early treatment arm.
- For patients included in the early treatment arm in complete remission, determine the
percentage achieving complete molecular remission using the clone-specific CDR-III
region as follow-up parameter.
- Determine the duration of response in patients included in the early treatment arm.
- Determine any adverse events related to treatment/safety of treatment.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk
factor profile (< 2 risk factors [low risk] vs ≥ 2 risk factors [high risk]). Low-risk
patients are assigned to arm II. High-risk patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive rituximab IV on day 1, fludarabine IV on days 1-3, and
cyclophosphamide IV on days 1-3. Treatment repeats every 28 days for up to 6 courses.
- Arm II: Patients undergo observation only until disease progression.
PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.
Allocation: Randomized, Primary Purpose: Treatment
Michael Hallek, MD
Medizinische Universitaetsklinik I at the University of Cologne