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: August 23, 2013
Last verified: July 2007
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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         
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         
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         
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         
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         
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         
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:
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: August 23, 2013
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 July 20, 2014