Fludarabine or Chlorambucil as First-Line Therapy in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

NCT ID: NCT00262795

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-30
• Study Completion Date: 2005-10-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine and chlorambucil, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether fludarabine is more effective than chlorambucil in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying fludarabine to see how well it works as first-line therapy compared to chlorambucil in treating older patients with previously untreated chronic lymphocytic leukemia.

Detailed Description

OBJECTIVES:

Primary

• Compare the overall and progression-free survival of older patients with previously untreated chronic lymphocytic leukemia treated with fludarabine vs chlorambucil.
• Compare the duration of remission in patients treated with these regimens.

Secondary

• Compare the incidence of toxicity, especially infections, in patients treated with these regimens.
• Compare the quality of life in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fludarabine IV on days 1-5. Treatment repeats every 28 days for up to 6 courses.
• Arm II: Patients receive oral chlorambucil on day 1. Treatment repeats every 15 days for up to 12 months.

PROJECTED ACCRUAL: A total of 205 patients will be accrued for this study.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

F

Fludarabine

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Fludarabine i.v. (25 mg/m2/d, d1-5) q28d; max 6 cycles

CLB

Chlorambucil

Group Type: ACTIVE_COMPARATOR

Chlorambucil

Intervention Type: DRUG

Chlorambucil p.o. (0,4 mg - max. 0,8 mg/kg/d, d1) q15d, max. 12 month

Interventions

Fludarabine

Fludarabine i.v. (25 mg/m2/d, d1-5) q28d; max 6 cycles

Intervention Type: DRUG

Chlorambucil

Chlorambucil p.o. (0,4 mg - max. 0,8 mg/kg/d, d1) q15d, max. 12 month

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of chronic lymphocytic leukemia, meeting any of the following staging criteria:

• Binet stage A with B symptoms
• Binet stage B or C, meeting 1 of the following criteria:

• Rapid disease progression
• Enlarged lymph nodes and organs
• Severe B symptoms
• Previously untreated disease

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• More than 6 months

Hematopoietic

• No thrombocytopenia
• No autoimmune hemolytic anemia

Hepatic

• Not specified

Renal

• Not specified

Other

• No severe organ dysfunction
• No other prior or concurrent neoplasm

PRIOR CONCURRENT THERAPY:

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German CLL Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Hallek, MD

Role: STUDY_CHAIR

Medizinische Universitaetsklinik I at the University of Cologne

Locations

Hanuschkrankenhaus

Vienna, , Austria

Klinikum St. Marien

Amberg, , Germany

Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie

Ansbach, , Germany

Zentralklinikum Augsburg

Augsburg, , Germany

Humaine - Clinic

Bad Saarow, , Germany

Krankenhaus Hohe Warte Mediziniche Klinik

Bayreuth, , Germany

Onkologisches Versorgungszentrum Friedrichshain

Berlin, , Germany

Internistische Gemeinschaftspraxis - Berlin

Berlin, , Germany

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

Charite - Campus Virchow Klinikum

Berlin, , Germany

Saint Josef - Hospital Bochum

Bochum, , Germany

Praxis Dres. F.& G. Doering

Bremen, , Germany

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, , Germany

Onkologische Schwerpunktpraxis

Cottbus, , Germany

Onkologische Gemeinschaftspraxis - Dresden

Dresden, , Germany

Krankenhaus Benrath

Düsseldorf, , Germany

Hans - Susemihl - Krankenhaus

Emden, , Germany

Kreiskrankenhaus Erding

Erding, , Germany

Internistische/Onkologische Praxis - Erfurt

Erfurt, , Germany

Helios Klinikum Erfurt

Erfurt, , Germany

Onkologische Schwerpunkt Praxis

Erlangen, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Evangelisches Krankenhaus Essen Werden

Essen, , Germany

Gemeinschaftspraxis - Freiburg

Freiburg im Breisgau, , Germany

Klinikum Garmisch - Partenkirchen

Garmisch-Partenkirchen, , Germany

Gemeinschaftspraxis Innere Medizin Hämatologie/Onkologie - Gera

Gera, , Germany

Internistische Praxis - Gerlingen

Gerlingen, , Germany

Internistische Praxisgemeinschaft

Germering, , Germany

Universitaetsklinikum Goettingen

Göttingen, , Germany

Internistisch-Haematologische Gemeinschaftspraxis - Gustrow

Güstrow, , Germany

Internistische Praxis - Halle

Halle, , Germany

Internistische Gemeinschaftspraxis - Halle

Halle, , Germany

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

St. Marien-Hospital Hamm - Klinik Knappenstrasse

Hamm, , Germany

Schwerpunktpraxis Haematologie/Onkologie - Hannover

Hanover, , Germany

Eichsfeld Klinikum gGmbH

Heiligenstadt, , Germany

Medizinischen Klinik Dr. R. Schindlbeck

Herrsching am Ammersee, , Germany

Oncological Specialist Practice

Hildesheim, , Germany

Universitaetsklinikum des Saarlandes

Homburg, , Germany

Clinic for Bone Marrow Transplantation and Hematology and Oncology

Idar-Oberstein, , Germany

Westpfalz-Klinikum GmbH

Kaiserslautern, , Germany

Staedt Klinikum Karlsruhe GGMBH

Karlsruhe, , Germany

Internistische Gemeinschaftspraxis - Kassel

Kassel, , Germany

Staedtische Krankenhaus Kiel

Kiel, , Germany

Krankenhaus Maria-Hilf Krefeld

Krefeld, , Germany

Internistische Onkologische Praxis - Kronach

Kronach, , Germany

Internistische Praxis - Landshut

Landshut, , Germany

Klinikum Lippe - Lemgo

Lemgo, , Germany

Internistische Praxis - Ludwigsburg

Ludwigsburg, , Germany

Kreiskrankenhaus Luedenscheid

Lüdenscheid, , Germany

III Medizinische Klinik Mannheim

Mannheim, , Germany

Regional Hospital Munchberg

Munchber, , Germany

Klinikum Innenstadt

Munich, , Germany

Krankenhaus Muenchen Schwabing

Munich, , Germany

Hamatologische Schwerpunktpraxis

Munich, , Germany

Munich Oncologic Practice at Elisenhof

Munich, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Staedtisches Krankenhaus Muenchen - Harlaching

Munich, , Germany

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, , Germany

Hamatologie/Onkologie Praxisgemeinschaft - Munchen

München, , Germany

Haematologisch-onkologische Gemeinschaftspraxis - Muenster

Münster, , Germany

Onkologische Schwerpunktpraxis Dr. Schmidt

Neunkirchen, , Germany

Praxis fuer Haematologie und Interne Onkologie

Norderstedt, , Germany

Praxisklinik fuer Innere Medizin - Nuernberg

Nuremberg, , Germany

Klinikum Nuernberg - Klinikum Nord

Nuremberg, , Germany

Internistische Gemeinschaftspraxis - Oberstaufen

Oberstaufen, , Germany

Internistische Gemeinschaftspraxis - Offenbach

Offenbach, , Germany

Internistische Gemeinschaftspraxis - Oldenburg

Oldenburg, , Germany

Klinikum Ernst Von Bergmann

Postdam, , Germany

Haematologische/Onkologische Schwerpunktpraxis - Rostock

Rostock, , Germany

Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock

Rostock, , Germany

Internistische Schwerpunktpraxis

Rüsselsheim am Main, , Germany

Schwerpunktpraxis Fuer Haematologie Und Onkologie

Saarbruecke, , Germany

Internistische Gemeinschaftspraxis - Saarbruecken

Saarbrücken, , Germany

Caritasklinik St. Theresia

Saarbrücken, , Germany

Kliniken Landkreis Sigmaringen GMBH

Sigmaringen, , Germany

Internistische Gemeinschaftspraxis - Stuttgart

Stuttgart, , Germany

Marienhospital Stuttgart

Stuttgart, , Germany

Haematologische Praxis

Stuttgart, , Germany

Klinik fuer Onkologie - Katharinenhospital Stuttgart

Stuttgart, , Germany

Onkologische Gemeinschaftspraxis - Trier

Trier, , Germany

Krankenanstalt Mutterhaus der Borromaerinnen

Trier, , Germany

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

St. Marien Hospital

Vechta, , Germany

Gemeinschaftspraxis

Worms, , Germany

Kliniken St. Antonius

Wuppertal, , Germany

Hamatologisch - Onkologische Praxis Wurzburg

Würzburg, , Germany

Countries

Austria; Germany

References

Eichhorst BF, Fischer K, Fink AM, Elter T, Wendtner CM, Goede V, Bergmann M, Stilgenbauer S, Hopfinger G, Ritgen M, Bahlo J, Busch R, Hallek M; German CLL Study Group (GCLLSG). Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis. Blood. 2011 Feb 10;117(6):1817-21. doi: 10.1182/blood-2010-04-282228. Epub 2010 Dec 7.

Reference Type: BACKGROUND

PMID: 21139079 (View on PubMed)

Cramer P, Bahlo J, Eichhorst B, Fischer K, Hallek M. Extramedullary manifestations of chronic lymphocytic leukaemia are not unusual. Leuk Res. 2014 Mar;38(3):284-5. doi: 10.1016/j.leukres.2013.11.015. Epub 2013 Dec 1. No abstract available.

Reference Type: BACKGROUND

PMID: 24412156 (View on PubMed)

Goede V, Cramer P, Busch R, Bergmann M, Stauch M, Hopfinger G, Stilgenbauer S, Dohner H, Westermann A, Wendtner CM, Eichhorst B, Hallek M; German CLL Study Group. Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials. Haematologica. 2014 Jun;99(6):1095-100. doi: 10.3324/haematol.2013.096792. Epub 2014 Feb 28.

Reference Type: BACKGROUND

PMID: 24584349 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31092457 (View on PubMed)

Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, Kranzhofer N, Rohrberg R, Soling U, Burkhard O, Westermann A, Goede V, Schweighofer CD, Fischer K, Fink AM, Wendtner CM, Brittinger G, Dohner H, Emmerich B, Hallek M; German CLL Study Group (GCLLSG). First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009 Oct 15;114(16):3382-91. doi: 10.1182/blood-2009-02-206185. Epub 2009 Jul 15.

Reference Type: RESULT

PMID: 19605849 (View on PubMed)

Other Identifiers

EU-20557

Identifier Type: -

Identifier Source: secondary_id

MEDAC-GCLLSG-CLL5

Identifier Type: -

Identifier Source: secondary_id

GCLLSG-73

Identifier Type: -

Identifier Source: secondary_id

CLL5

Identifier Type: -

Identifier Source: org_study_id