Rituximab, Fludarabine, and Cyclophosphamide or Observation Alone in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia
Overview[ - collapse ][ - ]
| Purpose | 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 | Leukemia |
| Intervention | Biological: rituximab Drug: cyclophosphamide Drug: fludarabine phosphate |
| Phase | Phase 3 |
| Sponsor | German CLL Study Group |
| Responsible Party | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier | NCT00275054 |
| First Received | January 10, 2006 |
| Last Updated | August 23, 2013 |
| Last verified | July 2007 |
Tracking Information[ + expand ][ + ]
| First Received Date | January 10, 2006 |
|---|---|
| Last Updated Date | August 23, 2013 |
| Start Date | October 2005 |
| Estimated Primary Completion Date | Not Provided |
| Current Primary Outcome Measures |
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| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Rituximab, Fludarabine, and Cyclophosphamide or Observation Alone in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia |
|---|---|
| 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 |
| 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 Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Primary Purpose: Treatment |
| Condition | Leukemia |
| Intervention | Biological: rituximab Drug: cyclophosphamide Drug: fludarabine phosphate |
| Study Arm (s) | Not Provided |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 600 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | Not Provided |
| Eligibility Criteria | DISEASE CHARACTERISTICS: - Established diagnosis of B-cell chronic lymphocytic leukemia - First diagnosis within 12 months before inclusion in study - Previously untreated disease - Binet stage A disease (Rai stage 0, I, or II) PATIENT CHARACTERISTICS: - Life expectancy > 6 months - ECOG performance status 0-2 - Willingness to accept contraception (if randomized to arm I) for the duration of therapy and 12 months thereafter - Negative serum pregnancy test - All parameters for risk stratification (lymphocyte doubling time, cytogenetics, unmutated IgVH, and serum thymidine kinase level > 10) present PRIOR CONCURRENT THERAPY: - No prior chemotherapy, radiotherapy, or antibody treatment - No other concurrent chemotherapy |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | Austria, France, Germany |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00275054 |
|---|---|
| Other Study ID Numbers | CDR0000455569 |
| Has Data Monitoring Committee | Not Provided |
| Information Provided By | National Cancer Institute (NCI) |
| Study Sponsor | German CLL Study Group |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Michael Hallek, MD Medizinische Universitaetsklinik I at the University of Cologne |
| Verification Date | July 2007 |
Locations[ + expand ][ + ]
| Universitaetsklinik fuer Innere Medizin I | Vienna, Austria, A-1090 Contact: Gaiger | 43-1-40-400-4445Recruiting |
|---|---|
| Centre Hospitalier Universitaire d'Amiens | Amiens, France, 80054 Contact: Jean-Pierre Marolleau, MD | 33-3-2245-5914 | marolleau.jean-pierre@chu-amiens.frRecruiting |
| Centre Hospitalier Regional et Universitaire d'Angers | Angers, France, 49033 Contact: Norbert Ifrah, MD | 33-2-41-35-4472Recruiting |
| Centre Hospitalier Victor Dupouy | Argenteuil, France, 95107 Contact: Laurent Sutton | 33-1-3423-2405Recruiting |
| Hopital Avicenne | Bobigny, France, 93009 Contact: Florence Ajchenbaum-Cymbalista, MD, PhD | 33-1-489-55-640 | florence.cymbalista@avc.aphp.frRecruiting |
| CHU de Caen | Caen, France, 14033 Contact: Michel Leporrier, MD | 33-312-725-39 | leporrier-m@chu-caen.frRecruiting |
| CHR Clermont Ferrand, Hotel Dieu | Clermont-Ferrand, France, 63058 Contact: Olivier Tournilhac, MD, PhD | 33-4-7375-0065Recruiting |
| Centre Hospitalier Universitaire Henri Mondor | Creteil, France, 94000 Contact: Marine Divine, MD | 33-1-49-814-174Recruiting |
| CHU de Grenoble - Hopital de la Tronche | Grenoble, France, 38043 Contact: Brigitte Pegourie, MD | 33-4-7676-5590Recruiting |
| Centre Jean Bernard | Le Mans, France, 72000 Contact: Philippe Solal-Celigny, MD, PhD | 33-2-4339-1300Recruiting |
| Centre Hospital Universitaire Hop Huriez | Lille, France, 59037 Contact: Bruno Cazin, MD | 33-3-2044-4290Recruiting |
| Hopital Edouard Herriot - Lyon | Lyon, France, 69437 Contact: Mauricette Michallet, MD | 33-472117401Recruiting |
| Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes | Marseille, France, 13273 Contact: Reda Bouabdallah, MD | 33-4-91-22-38-68 | hemato1@marseille.Fnclcc.frRecruiting |
| Centre Hospitalier de Meaux | Meaux, France, 77104 Contact: Wajed Abarah | 33-16-435-1266Recruiting |
| CHR Hotel Dieu | Nantes, France, 44093 Contact: Beatrice Mahe, MD | 33-2-4008-3271 | beatrice.mahe@chu-nantes.frRecruiting |
| Hopital Necker | Paris, France, 75743 Contact: Bruno R. Varet, MD | 33-1-44-495-282 | bruno.varet@nck.aphp.frRecruiting |
| Hopital Saint-Louis | Paris, France, 75475 Contact: Vincent Levy, MD, PhD | 33-14-249-4787Recruiting |
| CHU Pitie-Salpetriere | Paris, France, 75651 Contact: Veronique Leblond, MD | 33-1-4216-2824 | veronique.leblond@psl.aphp.frRecruiting |
| Hopital Haut Leveque | Pessac, France, 33604 Contact: Noel Milpied | 33-5-5765-6511Recruiting |
| Centre Hospitalier Lyon Sud | Pierre Benite, France, 69495 Contact: Gilles A. Salles, MD, PhD | 33-478-864-302 | gilles.galles@chu-lyon.frRecruiting |
| CHU Poitiers | Poitiers, France, 86021 Contact: Brigitte Dreyfus | 33-5-4944-4307Recruiting |
| CHU - Robert Debre | Reims, France, 51092 Contact: Alain Delmer, MD | 33-3-2678-3644 | adelmer@chu-reims.frRecruiting |
| Centre Henri Becquerel | Rouen, France, 76038 Contact: Stephane Lepretre, MD | 33-2-3208-2223Recruiting |
| Hopital Universitaire Hautepierre | Strasbourg, France, 67098 Contact: R. Herbrecht, MD | 33-388-127-688 | raoul.herbrecht@chru-strasbourg.frRecruiting |
| CHU de Toulouse, Hotel Dieu | Toulouse, France, 31059 Contact: Loic Ysebaert | 33-5-6177-2233Recruiting |
| CHU de Nancy - Hopitaux de Brabois | Vandoeuvre-Les-Nancy, France, 54511 Contact: Pierre Feugier | 33-3-8315-3705Recruiting |
| Praxis fuer Innere Medizin Haematologie und Internistische Onkologie | Alsfeld, Germany, 36304 Contact: Simone-Becker, MDRecruiting |
| Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg | Augsburg, Germany, 86150 Contact: Olaf Brudler, MD | 49-821-344-650Recruiting |
| Kreiskrankenhaus Aurich | Aurich, Germany, 26603 Contact: Langer, MD | 49-4941-94-5000 | langer@kkh-aurich.deRecruiting |
| Klinikum am Bamberg | Bamberg, Germany, 96049 Contact: Stefan Fries, MD | 49-951-7003-6230Recruiting |
| St. Hedwig Krankenhaus | Berlin, Germany, D-10115 Contact: Bernd Oldenkott, MD | 49-30-2311-2866Recruiting |
| Internistische Gemeinschaftspraxis - Berlin | Berlin, Germany, 13347 Contact: StrohbachRecruiting |
| Internistische Gemeinschaftspraxis Betzdorf | Betzdorf, Germany, D-57518 Contact: Martin Kerschbaum, MD | 49-2741-975-670Recruiting |
| DIAKO Ev. Diakonie Krankenhaus gGmbH | Bremen, Germany, D-28239 Contact: Karl-Heinz Pflueger, MD | 49-421-6102-1481 | pfluegerkh@diako-bremen.deRecruiting |
| Onkologische Schwerpunktpraxis at Facharzt fuer Innere Medizin | Coesfeld, Germany, 48653 Contact: Manfred Glados | 49-2541-971-893Recruiting |
| Praxis Fuer Haematologie Internistische Onkologie | Cologne, Germany, D-50677 Contact: C. Gabor, MD | 49-221-931-8220Recruiting |
| Medizinische Universitaetsklinik I at the University of Cologne | Cologne, Germany, D-50924 Contact: Barbara Eichhorst, MD | 49-221-478-4400 | barbara.eichhorst@uk-koeln.deRecruiting |
| Universitaetsklinikum Duesseldorf | Duesseldorf, Germany, D-40225 Contact: Habersang | 49-211-311-7990Recruiting |
| Helios Klinikum Erfurt | Erfurt, Germany, 99012 Contact: Michael Herold, MD, PhD | 49-361-781-5205Recruiting |
| Onkologische Schwerpunkt Praxis | Erlangen, Germany, D-91052 Contact: M. J. Eckart, MD | 49-9131-7625-0Recruiting |
| St. Antonius Hospital | Eschweiler, Germany, DOH-52249 Contact: Roland Fuchs, MD | 49-240-376-1280 | info@onkologie-eschweiler.deRecruiting |
| Universitaetsklinikum Essen | Essen, Germany, D-45122 Contact: J. Duerig | 49-201-723-2321Recruiting |
| Internistische Gemeinschaftspraxis - Forchheim | Forchheim, Germany, 91301 Contact: ThiemannRecruiting |
| Klinikum Frankfurt (Oder) GmbH | Frankfurt (Oder), Germany, D-15236 Contact: Michael G. Kiehl, MD, PhD | 49-335-548-4600 | m.kiehl.km@klinikumffo.deRecruiting |
| Internistische Gemeinschaftspraxis - Friedberg | Friedberg, Germany, 86316 Contact: Ripper, MDRecruiting |
| Germany | Fuerstenzell, Germany, 94981 Contact: Christine Baer, MD | 49-8502-8182Recruiting |
| Klinikum Garmisch - Partenkirchen GmbH | Garmisch-Partenkirchen, Germany, D-82467 Contact: L. Schulz, MD | 49-8821-77-1520 | lothar.schulz@klinikum-gap.deRecruiting |
| Internistische Praxisgemeinschaft | Germering, Germany, 82110 Contact: Johann Mittermueller, MD | 49-89-842-910Recruiting |
| Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie | Giessen, Germany, 35392 Contact: G. Schliesser, MD | 49-641-94-46-10Recruiting |
| Universitaetsklinikum Goettingen | Gottingen, Germany, D-37075 Contact: Claudia Binder, MD, PhD | 49-551-39-2331Recruiting |
| Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet | Greifswald, Germany, D-17475 Contact: C. Lotze, MD | 49-3834-866-700Recruiting |
| Maria-Josef-Hospital Greven GmbH | Greven, Germany, 48268 Contact: Nischik, MD | 49-2571-502-0Recruiting |
| St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH | Hagen, Germany, D-58095 Contact: Lindemann | 49-2331-129-250Recruiting |
| Universitaetsklinikum Halle | Halle, Germany, D-06120 Contact: Hans-Heinrich Wolf, MD | 49-345-557-3273 | hans.wolf@medizin.uni-halle.deRecruiting |
| Internistische Gemeinschaftspraxis - Halle | Halle, Germany, 06110 Contact: Rohrberg | 49-345-682-360Recruiting |
| Krankenhaus Siloah - Medizinische Klinik II | Hannover, Germany, D-30449 Contact: Jordan | 49-7231-498-3701Recruiting |
| Praxis Dr. med Freddy Henne | Hechingen, Germany, D-72379 Contact: Freddy Henne, MD | 49-7471-91-314Recruiting |
| Universitatsklinikum Heidelberg | Heidelberg, Germany, D-69120 Contact: Manfred Hensel, MD | 49-6221-56-8001Recruiting |
| Westpfalz-Klinikum GmbH | Kaiserslautern, Germany, D-67653 Contact: Hartmut Link, MD, PhD | 49-631-203-1260 | hlink@westpfalz-klinikum.deRecruiting |
| Internistische Gemeinschaftspraxis - Kassel | Kassel, Germany, D-34117 Contact: U. Soeling | 49-561-739-3372 | dr@soeling.deRecruiting |
| University Hospital Schleswig-Holstein - Kiel Campus | Kiel, Germany, D-24116 Contact: Michael Kneba | 49-431-1697Recruiting |
| Internistische Onkologische Praxis - Kronach | Kronach, Germany, 96317 Contact: Stauch | 49-9261-624-8161Recruiting |
| Internistische Praxis - Landshut | Landshut, Germany, 84028 Contact: Ursula Vehling-Kaiser | 49-871-275-381Recruiting |
| Caritas - Krakenhaus Lebach | Lebach, Germany, 66822 Contact: Stephan Kremers, MD | 49-6881-501-217Recruiting |
| Onkologische Schwerpunktpraxis - Leer | Leer, Germany, D-26789 Contact: Lothar Mueller, MD | 49-491-987-910 | Lothar.Mueller@onkologie-leer.deRecruiting |
| Staedtisches Klinikum Magdeburg - Altstadt | Magdeburg, Germany, D-39104 Contact: Erika Kettner, MD | 49-391-791-4900Recruiting |
| Gemeinschaftspraxis | Mannheim, Germany, D-68161 Contact: Ploeger | 49-721-889-2678Recruiting |
| Klinikum Minden | Minden, Germany, D-32423 Contact: Heinrich Bodenstein, MD | 49-571-801-4810 | heinrich.bodenstein@klinikum.minden.deRecruiting |
| Haematologische Praxis - Moenchengladbach | Moenchengladbach, Germany, D-41239 Contact: Christian Beck, MD | 49-216-693-4360 | dr.beck@onko-praxis.comRecruiting |
| Germany | Monchenglasbach/Rheydt, Germany, D-41239 Contact: Ulrich Grabenhorst, MD | 49-2166-934360Recruiting |
| Hamatologie/Onkologie Praxisgemeinschaft - Muenchen | Munich, Germany, D-81245 Contact: Schmidt, MDRecruiting |
| Munich Oncologic Practice at Elisenhof | Munich, Germany, D-80335 Contact: Wolfgang Abenhardt, MD | 49-89-452-2560 | w.abenhardt@onkologie-elisenhof.deRecruiting |
| Haematologische Schwerpunktpraxis | Munich, Germany, D-81679 Contact: Helmut Hitz, MD | 49-89-9972-0275Recruiting |
| Klinikum Rechts Der Isar - Technische Universitaet Muenchen | Munich, Germany, D-81241 Contact: Contact Person | 49-89-829-660 | schmidt@onkologie-pasing.deRecruiting |
| Klinikum Schwaebisch Gmuend Stauferklinik | Mutlangen, Germany, D-73557 Contact: Holger Hebart, MD | 44-7171-701-1302 | holger.hebart@klinikum-sgd.deRecruiting |
| Internistische Gemeinschaftspraxis - Offenbach | Offenbach, Germany, D-63065 Contact: Ballo, MD | 49-69-81-26-26Recruiting |
| Internistische Gemeinschaftspraxis - Oldenburg | Oldenburg, Germany, D-26121 Contact: Reschke, MD | 49-441-973-6229Recruiting |
| Germany | Pforzheim, Germany, 75179 Contact: Yves Dencausse, MD | 49-7231-280-3780Recruiting |
| Internistische Schwerpunktpraxis | Russelsheim, Germany, 65428 Contact: M. Baldus, MD | 49-6142-940-321Recruiting |
| Schwerpunktpraxis fuer Haematologie und Onkologie | Saarbruecken, Germany, 66113 Contact: Georg Jacobs, MD | 49-681-473-575 | praxis@onkosaar.deRecruiting |
| Diakonie - Krankenhaus | Schwaebisch Hall, Germany, 74523 Contact: Thomas Geer, MD | 49-791-753-4411 | tgeer@diaksha.deRecruiting |
| St. Marien - Krankenhaus Siegen GMBH | Siegen, Germany, D-57072 Contact: Tobias Gaska, MD | 49-271-231-1311Recruiting |
| Germany | Singen, Germany, D-78224 Contact: Thomas Fietz, MD | 49-7731-65-444Recruiting |
| Diakonie Klinikum Stuttgart | Stuttgart, Germany, D-70176 Contact: Rudolf Mueck, MD | 49-711-991-3506Recruiting |
| Robert-Bosch-Krankenhaus | Stuttgart, Germany, 70376 Contact: Walter Aulitzky, MD | 49-711-8101-3506 | walter.aulitzky@rbk.deRecruiting |
| Onkologische Gemeinschaftspraxis - Trier | Trier, Germany, 54290 Contact: LaubensteinRecruiting |
| Universitaetsklinikum Tuebingen | Tuebingen, Germany, D-72076 Contact: Sokler | 49-7071-298-2087Recruiting |
| Praxis fuer Haematologie und Onkologie | Twistringen, Germany, D-27239 Contact: Georg Weissenborn, MD | 49-4243-602-714Recruiting |
| Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm | Ulm, Germany, D-89081 Contact: Hartmut Doehner, MD | 49-731-5002-4400 | hartmut.doehner@uniklinik-ulm.deRecruiting |
| St. Marienhospital - Vechta | Vechta, Germany, D-49377 Contact: J. Diers, MD | 49-4441-99-0Recruiting |
| Burkhard and Reimann Gemeinschaftspraxis | Worms, Germany, DOH-67547 Contact: Oswald Burkhard, MD | 49-62-416-606 | oswald.burkhard@gmx.deRecruiting |