NCT00275054

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
825

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Oct 2005

Longer than P75 for phase_3

Geographic Reach
3 countries

91 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2005

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

January 10, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 11, 2006

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2007

Completed
7.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2015

Completed
Last Updated

May 23, 2019

Status Verified

May 1, 2019

Enrollment Period

1.7 years

First QC Date

January 10, 2006

Last Update Submit

May 21, 2019

Conditions

Keywords

stage 0 chronic lymphocytic leukemiaB-cell chronic lymphocytic leukemiastage I chronic lymphocytic leukemiastage II chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (2)

  • Event-free survival

  • Development of a new prognostic staging system

Secondary Outcomes (10)

  • Progression free survival

  • Overall survival

  • Time to progression to Binet stages B and C

  • Time to treatment

  • Quality of life

  • +5 more secondary outcomes

Study Arms (3)

Cohort I (FCR)

EXPERIMENTAL

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.

Drug: FludarabineDrug: CyclophosphamideBiological: Rituximab

Cohort II (W&W)

NO INTERVENTION

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 II receive no treatment at all (watch \& wait).

Cohort III (W&W)

NO INTERVENTION

Patients with less than 2 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) are assigned directly to cohort III and receive no treatment at all (watch \& wait).

Interventions

cycles 1-6: 25 mg/m² i.v., d2-4, q28d

Also known as: Fludura
Cohort I (FCR)

cycles 1-6: 250 mg/m² i.v., d2-4, q28d

Also known as: Endoxan
Cohort I (FCR)
RituximabBIOLOGICAL

cycle1: 375 mg/m² i.v., d1, q28d cycles 2-6: 500 mg/m² i.v., d1, q28d

Also known as: Mabthera, Rituxan
Cohort I (FCR)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (91)

Universitaetsklinik fuer Innere Medizin I

Vienna, A-1090, Austria

Location

Centre Hospitalier Universitaire d'Amiens

Amiens, 80054, France

Location

Centre Hospitalier Regional et Universitaire d'Angers

Angers, 49033, France

Location

Centre Hospitalier Victor Dupouy

Argenteuil, 95107, France

Location

Hopital Avicenne

Bobigny, 93009, France

Location

CHU de Caen

Caen, 14033, France

Location

CHR Clermont Ferrand, Hotel Dieu

Clermont-Ferrand, 63058, France

Location

Centre Hospitalier Universitaire Henri Mondor

Créteil, 94000, France

Location

CHU de Grenoble - Hopital de la Tronche

Grenoble, 38043, France

Location

Centre Jean Bernard

Le Mans, 72000, France

Location

Centre Hospital Universitaire Hop Huriez

Lille, 59037, France

Location

Hopital Edouard Herriot - Lyon

Lyon, 69437, France

Location

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, 13273, France

Location

Centre Hospitalier de Meaux

Meaux, 77104, France

Location

CHR Hotel Dieu

Nantes, 44093, France

Location

Hopital Saint-Louis

Paris, 75475, France

Location

CHU Pitie-Salpetriere

Paris, 75651, France

Location

Hopital Necker

Paris, 75743, France

Location

Hopital Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Poitiers

Poitiers, 86021, France

Location

CHU - Robert Debre

Reims, 51092, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Hopital Universitaire Hautepierre

Strasbourg, 67098, France

Location

CHU de Toulouse, Hotel Dieu

Toulouse, 31059, France

Location

CHU de Nancy - Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Praxis fuer Innere Medizin Haematologie und Internistische Onkologie

Alsfeld, 36304, Germany

Location

Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg

Augsburg, 86150, Germany

Location

Kreiskrankenhaus Aurich

Aurich, 26603, Germany

Location

Klinikum am Bamberg

Bamberg, 96049, Germany

Location

Internistische Gemeinschaftspraxis - Berlin

Berlin, 13347, Germany

Location

St. Hedwig Krankenhaus

Berlin, D-10115, Germany

Location

Internistische Gemeinschaftspraxis Betzdorf

Betzdorf, D-57518, Germany

Location

DIAKO Ev. Diakonie Krankenhaus gGmbH

Bremen, D-28239, Germany

Location

Onkologische Schwerpunktpraxis at Facharzt fuer Innere Medizin

Coesfeld, 48653, Germany

Location

Praxis Fuer Haematologie Internistische Onkologie

Cologne, D-50677, Germany

Location

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, D-50924, Germany

Location

Universitaetsklinikum Duesseldorf

Düsseldorf, D-40225, Germany

Location

Helios Klinikum Erfurt

Erfurt, 99012, Germany

Location

Onkologische Schwerpunkt Praxis

Erlangen, D-91052, Germany

Location

St. Antonius Hospital

Eschweiler, DOH-52249, Germany

Location

Universitaetsklinikum Essen

Essen, D-45122, Germany

Location

Internistische Gemeinschaftspraxis - Forchheim

Forchheim, 91301, Germany

Location

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), D-15236, Germany

Location

Internistische Gemeinschaftspraxis - Friedberg

Friedberg, 86316, Germany

Location

Unknown Facility

Fürstenzell, 94981, Germany

Location

Klinikum Garmisch - Partenkirchen GmbH

Garmisch-Partenkirchen, D-82467, Germany

Location

Internistische Praxisgemeinschaft

Germering, 82110, Germany

Location

Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie

Giessen, 35392, Germany

Location

Universitaetsklinikum Goettingen

Göttingen, D-37075, Germany

Location

Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet

Greifswald, D-17475, Germany

Location

Maria-Josef-Hospital Greven GmbH

Greven, 48268, Germany

Location

St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

Hagen, D-58095, Germany

Location

Internistische Gemeinschaftspraxis - Halle

Halle, 06110, Germany

Location

Universitaetsklinikum Halle

Halle, D-06120, Germany

Location

Krankenhaus Siloah - Medizinische Klinik II

Hanover, D-30449, Germany

Location

Praxis Dr. med Freddy Henne

Hechingen, D-72379, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, D-69120, Germany

Location

Westpfalz-Klinikum GmbH

Kaiserslautern, D-67653, Germany

Location

Internistische Gemeinschaftspraxis - Kassel

Kassel, D-34117, Germany

Location

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, D-24116, Germany

Location

Internistische Onkologische Praxis - Kronach

Kronach, 96317, Germany

Location

Internistische Praxis - Landshut

Landshut, 84028, Germany

Location

Caritas - Krakenhaus Lebach

Lebach, 66822, Germany

Location

Onkologische Schwerpunktpraxis - Leer

Leer, D-26789, Germany

Location

Staedtisches Klinikum Magdeburg - Altstadt

Magdeburg, D-39104, Germany

Location

Gemeinschaftspraxis

Mannheim, D-68161, Germany

Location

Klinikum Minden

Minden, D-32423, Germany

Location

Unknown Facility

Monchenglasbach/Rheydt, D-41239, Germany

Location

Haematologische Praxis - Moenchengladbach

Mönchengladbach, D-41239, Germany

Location

Munich Oncologic Practice at Elisenhof

Munich, D-80335, Germany

Location

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, D-81241, Germany

Location

Hamatologie/Onkologie Praxisgemeinschaft - Muenchen

Munich, D-81245, Germany

Location

Haematologische Schwerpunktpraxis

Munich, D-81679, Germany

Location

Klinikum Schwaebisch Gmuend Stauferklinik

Mutlangen, D-73557, Germany

Location

Internistische Gemeinschaftspraxis - Offenbach

Offenbach, D-63065, Germany

Location

Internistische Gemeinschaftspraxis - Oldenburg

Oldenburg, D-26121, Germany

Location

Unknown Facility

Pforzheim, 75179, Germany

Location

Internistische Schwerpunktpraxis

Rüsselsheim am Main, 65428, Germany

Location

Schwerpunktpraxis fuer Haematologie und Onkologie

Saarbrücken, 66113, Germany

Location

Diakonie - Krankenhaus

Schwäbisch Hall, 74523, Germany

Location

St. Marien - Krankenhaus Siegen GMBH

Siegen, D-57072, Germany

Location

Unknown Facility

Singen, D-78224, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

Diakonie Klinikum Stuttgart

Stuttgart, D-70176, Germany

Location

Onkologische Gemeinschaftspraxis - Trier

Trier, 54290, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, D-72076, Germany

Location

Praxis fuer Haematologie und Onkologie

Twistringen, D-27239, Germany

Location

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Ulm, D-89081, Germany

Location

St. Marienhospital - Vechta

Vechta, D-49377, Germany

Location

Burkhard and Reimann Gemeinschaftspraxis

Worms, DOH-67547, Germany

Location

Related Publications (2)

  • Sachanas S, Pangalis GA, Fink AM, Bahlo J, Fischer K, Levidou G, Kyrtsonis MC, Bartzi V, Vassilakopoulos TP, Kalpadakis C, Koulieris E, Moschogiannis M, Yiakoumis X, Tsirkinidis P, Angelopoulou MK, Eichhorst B, Hallek M. Small Lymphocytic Lymphoma: Analysis of Two Cohorts Including Patients in Clinical Trials of the German Chronic Lymphocytic Leukemia Study Group (GCLLSG) or in "Real-Life" Outside of Clinical Trials. Anticancer Res. 2019 May;39(5):2591-2598. doi: 10.21873/anticanres.13382.

    PMID: 31092457BACKGROUND
  • Herling CD, Cymbalista F, Gross-Ophoff-Muller C, Bahlo J, Robrecht S, Langerbeins P, Fink AM, Al-Sawaf O, Busch R, Porcher R, Cazin B, Dreyfus B, Ibach S, Lepretre S, Fischer K, Kaiser F, Eichhorst B, Wentner CM, Hoechstetter MA, Dohner H, Leblond V, Kneba M, Letestu R, Bottcher S, Stilgenbauer S, Hallek M, Levy V. Early treatment with FCR versus watch and wait in patients with stage Binet A high-risk chronic lymphocytic leukemia (CLL): a randomized phase 3 trial. Leukemia. 2020 Aug;34(8):2038-2050. doi: 10.1038/s41375-020-0747-7. Epub 2020 Feb 18.

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabineCyclophosphamideRituximab

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Michael Hallek, MD

    Medizinische Universitaetsklinik I at the University of Cologne

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

January 10, 2006

First Posted

January 11, 2006

Study Start

October 1, 2005

Primary Completion

July 1, 2007

Study Completion

June 1, 2015

Last Updated

May 23, 2019

Record last verified: 2019-05

Data Sharing

IPD Sharing
Will not share

Locations