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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2007 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00275054
First received: January 10, 2006
Last updated: April 16, 2010
Last verified: July 2007
History of Changes
  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 Intervention Phase
Leukemia
 Biological: rituximab
Drug: cyclophosphamide
Drug: fludarabine phosphate
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival [ Designated as safety issue: No ]
  • Development of a new prognostic staging system [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Time to progression to Binet stages B and C [ Designated as safety issue: No ]
  • Time to treatment [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Pharmacoeconomic analysis [ Designated as safety issue: No ]
  • Overall response (complete and partial) rate in patients in the early treatment arm [ Designated as safety issue: No ]
  • Percentage of patients achieving complete molecular remission in the early treatment arm [ Designated as safety issue: No ]
  • Duration of response in patients in the early treatment arm [ Designated as safety issue: No ]
  • Adverse events in patients in the early treatment arm [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: October 2005
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00275054

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

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier: NCT00275054     History of Changes
Other Study ID Numbers: CDR0000455569, GCLLSG-CLL7, EU-20559, ROCHE-GCLLSG-CLL7, EUDRACT-2005-003-018-14
Study First Received: January 10, 2006
Last Updated: April 16, 2010
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage 0 chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Rituximab
Fludarabine
Vidarabine
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 19, 2013