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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00275054
• Other study ID #: CLL7
• Secondary ID: EU-20559ROCHE-GC
• Status: Completed
• Phase: Phase 3
• Start date: October 2005
• Est. completion date: June 2015

Study information

• Verified date: May 2019
• Source: German CLL Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 825
• Est. completion date: June 2015
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Fludarabine
cycles 1-6: 25 mg/m² i.v., d2-4, q28d
• Cyclophosphamide
cycles 1-6: 250 mg/m² i.v., d2-4, q28d

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

Locations

Country	Name	City	State
Austria	Universitaetsklinik fuer Innere Medizin I	Vienna
France	Centre Hospitalier Universitaire d'Amiens	Amiens
France	Centre Hospitalier Regional et Universitaire d'Angers	Angers
France	Centre Hospitalier Victor Dupouy	Argenteuil
France	Hopital Avicenne	Bobigny
France	CHU de Caen	Caen
France	CHR Clermont Ferrand, Hotel Dieu	Clermont-Ferrand
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	CHU de Grenoble - Hopital de la Tronche	Grenoble
France	Centre Jean Bernard	Le Mans
France	Centre Hospital Universitaire Hop Huriez	Lille
France	Hopital Edouard Herriot - Lyon	Lyon
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille
France	Centre Hospitalier de Meaux	Meaux
France	CHR Hotel Dieu	Nantes
France	CHU Pitie-Salpetriere	Paris
France	Hopital Necker	Paris
France	Hopital Saint-Louis	Paris
France	Hopital Haut Leveque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU Poitiers	Poitiers
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
Germany	Praxis fuer Innere Medizin Haematologie und Internistische Onkologie	Alsfeld
Germany	Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg	Augsburg
Germany	Kreiskrankenhaus Aurich	Aurich
Germany	Klinikum am Bamberg	Bamberg
Germany	Internistische Gemeinschaftspraxis - Berlin	Berlin
Germany	St. Hedwig Krankenhaus	Berlin
Germany	Internistische Gemeinschaftspraxis Betzdorf	Betzdorf
Germany	DIAKO Ev. Diakonie Krankenhaus gGmbH	Bremen
Germany	Onkologische Schwerpunktpraxis at Facharzt fuer Innere Medizin	Coesfeld
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Praxis Fuer Haematologie Internistische Onkologie	Cologne
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Onkologische Schwerpunkt Praxis	Erlangen
Germany	St. Antonius Hospital	Eschweiler
Germany	Universitaetsklinikum Essen	Essen
Germany	Internistische Gemeinschaftspraxis - Forchheim	Forchheim
Germany	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)
Germany	Internistische Gemeinschaftspraxis - Friedberg	Friedberg
Germany	Klinikum Garmisch - Partenkirchen GmbH	Garmisch-Partenkirchen
Germany	Internistische Praxisgemeinschaft	Germering
Germany	Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie	Giessen
Germany	Universitaetsklinikum Goettingen	Gottingen
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Maria-Josef-Hospital Greven GmbH	Greven
Germany	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH	Hagen
Germany	Internistische Gemeinschaftspraxis - Halle	Halle
Germany	Universitaetsklinikum Halle	Halle
Germany	Krankenhaus Siloah - Medizinische Klinik II	Hannover
Germany	Praxis Dr. med Freddy Henne	Hechingen
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	Internistische Gemeinschaftspraxis - Kassel	Kassel
Germany	University Hospital Schleswig-Holstein - Kiel Campus	Kiel
Germany	Internistische Onkologische Praxis - Kronach	Kronach
Germany	Internistische Praxis - Landshut	Landshut
Germany	Caritas - Krakenhaus Lebach	Lebach
Germany	Onkologische Schwerpunktpraxis - Leer	Leer
Germany	Staedtisches Klinikum Magdeburg - Altstadt	Magdeburg
Germany	Gemeinschaftspraxis	Mannheim
Germany	Klinikum Minden	Minden
Germany	Haematologische Praxis - Moenchengladbach	Moenchengladbach
Germany	Haematologische Schwerpunktpraxis	Munich
Germany	Hamatologie/Onkologie Praxisgemeinschaft - Muenchen	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Munich Oncologic Practice at Elisenhof	Munich
Germany	Klinikum Schwaebisch Gmuend Stauferklinik	Mutlangen
Germany	Internistische Gemeinschaftspraxis - Offenbach	Offenbach
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	Diakonie Klinikum Stuttgart	Stuttgart
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	Onkologische Gemeinschaftspraxis - Trier	Trier
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Praxis fuer Haematologie und Onkologie	Twistringen
Germany	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm
Germany	St. Marienhospital - Vechta	Vechta
Germany	Burkhard and Reimann Gemeinschaftspraxis	Worms

Sponsors (1)

Lead Sponsor	Collaborator
German CLL Study Group

Countries where clinical trial is conducted

Austria,  France,  Germany, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival
Primary	Development of a new prognostic staging system
Secondary	Progression free survival
Secondary	Overall survival
Secondary	Time to progression to Binet stages B and C
Secondary	Time to treatment
Secondary	Quality of life
Secondary	Pharmacoeconomic analysis
Secondary	Overall response (complete and partial) rate in patients in the early treatment arm
Secondary	Percentage of patients achieving complete molecular remission in the early treatment arm
Secondary	Duration of response in patients in the early treatment arm
Secondary	Adverse events in patients in the early treatment arm

External Links

•   Click here for more information about this study: CLL7 (German CLL Study Group)