Rituximab, Fludarabine, and Cyclophosphamide or Observation Alone in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia
|ClinicalTrials.gov Identifier: NCT00275054|
Recruitment Status : Completed
First Posted : January 11, 2006
Last Update Posted : October 3, 2016
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. 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. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether giving rituximab together with fludarabine and cyclophosphamide is more effective than observation alone in treating chronic lymphocytic leukemia.
PURPOSE: This randomized phase III trial is studying rituximab, fludarabine, and cyclophosphamide to see how well they work compared to observation alone in treating patients with stage 0, stage I, or stage II B-cell chronic lymphocytic leukemia.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Drug: Fludarabine Drug: Cyclophosphamide Biological: Rituximab||Phase 3|
- 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 progression.
- 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 regimens.
- Compare the overall and progression-free survival of patients treated with these regimens.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||825 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||October 2005|
|Actual Primary Completion Date :||July 2007|
|Actual Study Completion Date :||June 2015|
Experimental: Cohort I (FCR)
Patients with 2 or more risk factors out of 4 (1. unfavorable molecular cytogenetics, 2. high serum thymidine kinase levels, 3. lymphocyte doubling time shorter than 12 months, 4. unmutated IgVH gene) who are randomized into cohort I receive Fludarabine, Cyclophosphamide and Rituximab (FCR) chemoimmunotherapy.
cycles 1-6: 25 mg/m² i.v., d2-4, q28d
Other Name: FluduraDrug: Cyclophosphamide
cycles 1-6: 250 mg/m² i.v., d2-4, q28d
Other Name: EndoxanBiological: Rituximab
cycle1: 375 mg/m² i.v., d1, q28d
cycles 2-6: 500 mg/m² i.v., d1, q28d
No Intervention: Cohort II (W&W)
Patients with 2 or more risk factors out of 4 (1. unfavorable molecular cytogenetics, 2. high serum thymidine kinase levels, 3. lymphocyte doubling time shorter than 12 months, 4. unmutated IgVH gene) who are randomized into cohort II receive no treatment at all (watch & wait).
No Intervention: Cohort III (W&W)
Patients with less than 2 risk factors out of 4 (1. unfavorable molecular cytogenetics, 2. high serum thymidine kinase levels, 3. lymphocyte doubling time shorter than 12 months, 4. unmutated IgVH gene) are assigned directly to cohort III and receive no treatment at all (watch & wait).
- Event-free survival
- Development of a new prognostic staging system
- Progression free survival
- Overall survival
- Time to progression to Binet stages B and C
- Time to treatment
- Quality of life
- Pharmacoeconomic analysis
- Overall response (complete and partial) rate in patients in the early treatment arm
- Percentage of patients achieving complete molecular remission in the early treatment arm
- Duration of response in patients in the early treatment arm
- Adverse events in patients in the early treatment arm
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00275054
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|Principal Investigator:||Michael Hallek, MD||Medizinische Universitaetsklinik I at the University of Cologne|