Rituximab, Fludarabine, and Cyclophosphamide or Observation Alone in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia

Phase 3

Completed

• Conditions: Chronic Lymphocytic Leukemia
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Rituximab

• Registration Number: NCT00275054
• Lead Sponsor: German CLL Study Group

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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.

Secondary

* 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 Timeline

• Study Start: 2005-10
• Study First Submitted: 2006-01-10
• Study First Submitted QC: 2006-01-10
• Study First Posted: 2006-01-11
• Primary Completion: 2007-07
• Study Completion: 2015-06
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-21
• Last Update Posted: 2019-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 825

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort I (FCR)	Rituximab	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.
Cohort I (FCR)	Cyclophosphamide	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.
Cohort I (FCR)	Fludarabine	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.

Primary Outcome Measures

Name	Time	Method
Event-free survival
Development of a new prognostic staging system

Secondary Outcome Measures

Name	Time	Method
Progression free survival
Time to treatment
Quality of life
Overall response (complete and partial) rate in patients in the early treatment arm
Overall survival
Adverse events in patients in the early treatment arm
Time to progression to Binet stages B and C
Pharmacoeconomic analysis
Percentage of patients achieving complete molecular remission in the early treatment arm
Duration of response in patients in the early treatment arm

Trial Locations

Locations (87)

Universitaetsklinik fuer Innere Medizin I; 🇦🇹 Vienna, Austria

Centre Hospitalier Universitaire d'Amiens; 🇫🇷 Amiens, France

Centre Hospitalier Regional et Universitaire d'Angers; 🇫🇷 Angers, France

Centre Hospitalier Victor Dupouy; 🇫🇷 Argenteuil, France

Hopital Avicenne; 🇫🇷 Bobigny, France

CHU de Caen; 🇫🇷 Caen, France

CHR Clermont Ferrand, Hotel Dieu; 🇫🇷 Clermont-Ferrand, France

Centre Hospitalier Universitaire Henri Mondor; 🇫🇷 Creteil, France

CHU de Grenoble - Hopital de la Tronche; 🇫🇷 Grenoble, France

Centre Jean Bernard; 🇫🇷 Le Mans, France

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