Rituximab, Fludarabine, and Cyclophosphamide or Observation Alone in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 825
Not provided
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 Time to treatment Progression free survival 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
CHU Poitiers
🇫🇷Poitiers, France
St. Hedwig Krankenhaus
🇩🇪Berlin, Germany
Praxis Fuer Haematologie Internistische Onkologie
🇩🇪Cologne, Germany
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
🇫🇷Marseille, France
Hopital Haut Leveque
🇫🇷Pessac, France
Praxis fuer Innere Medizin Haematologie und Internistische Onkologie
🇩🇪Alsfeld, Germany
Hopital Edouard Herriot - Lyon
🇫🇷Lyon, France
Hopital Avicenne
🇫🇷Bobigny, France
Centre Hospital Universitaire Hop Huriez
🇫🇷Lille, France
Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil, France
Centre Hospitalier Universitaire Henri Mondor
🇫🇷Creteil, France
Hopital Saint-Louis
🇫🇷Paris, France
Centre Hospitalier de Meaux
🇫🇷Meaux, France
Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
🇩🇪Augsburg, Germany
DIAKO Ev. Diakonie Krankenhaus gGmbH
🇩🇪Bremen, Germany
Internistische Gemeinschaftspraxis Betzdorf
🇩🇪Betzdorf, Germany
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Internistische Gemeinschaftspraxis - Friedberg
🇩🇪Friedberg, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Maria-Josef-Hospital Greven GmbH
🇩🇪Greven, Germany
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Klinikum Garmisch - Partenkirchen GmbH
🇩🇪Garmisch-Partenkirchen, Germany
Internistische Praxisgemeinschaft
🇩🇪Germering, Germany
Internistische Gemeinschaftspraxis - Halle
🇩🇪Halle, Germany
Praxis fuer Haematologie und Onkologie
🇩🇪Twistringen, Germany
CHR Hotel Dieu
🇫🇷Nantes, France
CHU Pitie-Salpetriere
🇫🇷Paris, France
Hopital Necker
🇫🇷Paris, France
CHU - Robert Debre
🇫🇷Reims, France
Centre Henri Becquerel
🇫🇷Rouen, France
Hopital Universitaire Hautepierre
🇫🇷Strasbourg, France
CHU de Toulouse, Hotel Dieu
🇫🇷Toulouse, France
CHU de Nancy - Hopitaux de Brabois
🇫🇷Vandoeuvre-Les-Nancy, France
Medizinische Universitaetsklinik I at the University of Cologne
🇩🇪Cologne, Germany
Universitaetsklinikum Duesseldorf
🇩🇪Duesseldorf, Germany
Onkologische Schwerpunkt Praxis
🇩🇪Erlangen, Germany
St. Antonius Hospital
🇩🇪Eschweiler, Germany
Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
🇩🇪Greifswald, Germany
Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
🇩🇪Giessen, Germany
Universitaetsklinikum Goettingen
🇩🇪Gottingen, Germany
St. Marienhospital - Vechta
🇩🇪Vechta, Germany
Burkhard and Reimann Gemeinschaftspraxis
🇩🇪Worms, Germany
Centre Hospitalier Regional et Universitaire d'Angers
🇫🇷Angers, France
Centre Hospitalier Universitaire d'Amiens
🇫🇷Amiens, France
CHR Clermont Ferrand, Hotel Dieu
🇫🇷Clermont-Ferrand, France
Centre Jean Bernard
🇫🇷Le Mans, France
CHU de Caen
🇫🇷Caen, France
CHU de Grenoble - Hopital de la Tronche
🇫🇷Grenoble, France
Klinikum am Bamberg
🇩🇪Bamberg, Germany
Internistische Gemeinschaftspraxis - Berlin
🇩🇪Berlin, Germany
Kreiskrankenhaus Aurich
🇩🇪Aurich, Germany
Onkologische Schwerpunktpraxis at Facharzt fuer Innere Medizin
🇩🇪Coesfeld, Germany
Klinikum Frankfurt (Oder) GmbH
🇩🇪Frankfurt (Oder), Germany
St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
🇩🇪Hagen, Germany
Universitaetsklinikum Halle
🇩🇪Halle, Germany
Praxis Dr. med Freddy Henne
🇩🇪Hechingen, Germany
Krankenhaus Siloah - Medizinische Klinik II
🇩🇪Hannover, Germany
Westpfalz-Klinikum GmbH
🇩🇪Kaiserslautern, Germany
Internistische Gemeinschaftspraxis - Kassel
🇩🇪Kassel, Germany
University Hospital Schleswig-Holstein - Kiel Campus
🇩🇪Kiel, Germany
Universitatsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Internistische Onkologische Praxis - Kronach
🇩🇪Kronach, Germany
Internistische Praxis - Landshut
🇩🇪Landshut, Germany
Caritas - Krakenhaus Lebach
🇩🇪Lebach, Germany
Onkologische Schwerpunktpraxis - Leer
🇩🇪Leer, Germany
Klinikum Minden
🇩🇪Minden, Germany
Staedtisches Klinikum Magdeburg - Altstadt
🇩🇪Magdeburg, Germany
Gemeinschaftspraxis
🇩🇪Mannheim, Germany
Munich Oncologic Practice at Elisenhof
🇩🇪Munich, Germany
Haematologische Praxis - Moenchengladbach
🇩🇪Moenchengladbach, Germany
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
🇩🇪Munich, Germany
Hamatologie/Onkologie Praxisgemeinschaft - Muenchen
🇩🇪Munich, Germany
Haematologische Schwerpunktpraxis
🇩🇪Munich, Germany
Internistische Gemeinschaftspraxis - Offenbach
🇩🇪Offenbach, Germany
Klinikum Schwaebisch Gmuend Stauferklinik
🇩🇪Mutlangen, Germany
Internistische Gemeinschaftspraxis - Oldenburg
🇩🇪Oldenburg, Germany
Internistische Schwerpunktpraxis
🇩🇪Russelsheim, Germany
Schwerpunktpraxis fuer Haematologie und Onkologie
🇩🇪Saarbruecken, Germany
Diakonie - Krankenhaus
🇩🇪Schwäbisch Hall, Germany
St. Marien - Krankenhaus Siegen GMBH
🇩🇪Siegen, Germany
Robert-Bosch-Krankenhaus
🇩🇪Stuttgart, Germany
Onkologische Gemeinschaftspraxis - Trier
🇩🇪Trier, Germany
Diakonie Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Internistische Gemeinschaftspraxis - Forchheim
🇩🇪Forchheim, Germany