Fludarabine With or Without Cyclophosphamide in Treating Patients With Advanced Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Fludarabine Versus Fludarabine Plus Cyclophosphamide in First Line Therapy of Younger Patients (Up to 65 Years) With Advanced Chronic Lymphocytic Leukemia (CLL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00276848
• Other study ID #: CLL4
• Secondary ID: EU-20538GCLLSG-1
• Status: Completed
• Phase: Phase 3
• Start date: July 1999
• Est. completion date: July 2007

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: 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. It is not yet known whether giving fludarabine together with cyclophosphamide is more effective than fludarabine alone in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying giving fludarabine together with cyclophosphamide to see how well it works compared to fludarabine alone in treating patients with advanced chronic lymphocytic leukemia.

Description:

OBJECTIVES:

Primary

• Compare the progression-free survival, as well the overall survival and duration of remission in patients with previously untreated, advanced chronic lymphocytic leukemia treated with fludarabine with versus without cyclophosphamide.

Secondary

• Compare the incidence of side effects and quality of life of patients treated with these drugs.

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

• Arm I: Patients receive fludarabine IV on days 1-5.

• Arm II: Patients receive fludarabine IV and cyclophosphamide IV on days 1-3. In both arms, treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 375
• Est. completion date: July 2007
• Est. primary completion date: July 2003
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of previously untreated chronic lymphocytic leukemia (CLL)

• Binet stage C and stage B are acceptable if there is rapid disease progression, symptoms of enlarged lymph nodes and organs, or severe B-symptoms

• Binet stage A is acceptable, if there are B-symptoms

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy > 6 months

• No severe organ dysfunction

• No other previous or concurrent neoplasms, autoimmune hemolytic anemia, or thrombocytopenia

PRIOR CONCURRENT THERAPY:

• No prior or concurrent chemotherapy

Related Conditions & MeSH terms

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

Intervention

Drug:
• Fludarabine plus Cyclophosphamide
fludarabine at a dose of 25 mg/m2, administered intravenously daily over 30 minutes for 5 days, or fludarabine dosed at 30 mg/m2, administered intravenously daily over 30 minutes for 3 days, plus cyclophosphamide dosed at 250 mg/m2, administered intravenously daily over 30 minutes for 3 days, repeated every 28 days for a maximum of 6 courses
• Fludarabine
fludarabine at a dose of 25 mg/m2, administered intravenously daily over 30 minutes for 5 days, or fludarabine dosed at 30 mg/m2, administered intravenously daily over 30 minutes for 3 days, , repeated every 28 days for a maximum of 6 courses

Locations

Country	Name	City	State
Austria	Allgemeines Krankenhaus - Universitatskliniken	Vienna
Austria	Hanuschkrankenhaus	Vienna
Germany	Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie	Ansbach
Germany	Internistische Praxis - Arnstadt	Arnstadt
Germany	Specialist Practice for Oncology	Aschaffenburg
Germany	Klinikum Augsburg	Augsburg
Germany	Kreiskrankenhaus Aurich	Aurich
Germany	Kreiskrankenhaus	Bad Hersfeld
Germany	Caritas-Krankenhaus Bad Mergentheim	Bad Mergentheim
Germany	Humaine - Clinic	Bad Saarow
Germany	Internistische Praxis - Bad Salzuflen	Bad Salzuflen
Germany	Internistische Praxis - Bayreuth	Bayreuth
Germany	Internistische Gemeinschaftspraxis - Bergisch Gladbach	Bergisch Gladbach
Germany	Charite - Campus Charite Mitte	Berlin
Germany	Charite - Campus Virchow Klinikum	Berlin
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Evang. Waldkrankenhaus Spandau	Berlin
Germany	Internistische Gemeinschaftspraxis - Berlin	Berlin
Germany	Internistische Gemeinschaftspraxis - Berlin	Berlin
Germany	Internistische Praxis - Berlin	Berlin
Germany	Onkolog - Haematolog Schwerpunktpraxis	Berlin
Germany	Onkologische Gemeinschaftspraxis - Berlin	Berlin
Germany	Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch	Berlin
Germany	Krankenhaus Bietigheim	Bietigheim
Germany	DIAKO Ev. Diakonie Krankenhaus gGmbH	Bremen
Germany	Internistische Praxis - Chemnitz	Chemnitz
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Onkologische Schwerpunktpraxis	Cottbus
Germany	Onkologische Gemeinschaftspraxis - Dresden	Dresden
Germany	Krankenhaus Benrath	Dusseldorf
Germany	St. Georg Klinikum Eisenach GmbH	Eisenach
Germany	Hans - Susemihl - Krankenhaus	Emden
Germany	Internistische/Onkologische Praxis - Erfurt	Erfurt
Germany	Klinikum Erfurt	Erfurt
Germany	Praxis DR. J. Weniger	Erfurt
Germany	Praxis fuer Haematologie/Onkologie - Erfurt	Erfurt
Germany	Onkologische Schwerpunkt Praxis	Erlangen
Germany	St. Antonius Hospital	Eschweiler
Germany	Evangelisches Krankenhaus Essen Werden	Essen
Germany	Onkologische Praxis - Essen	Essen
Germany	Universitaetsklinikum Essen	Essen
Germany	Staedtische Kliniken Esslingen	Esslingen
Germany	Internistische Gemeinschaftspraxis - Forchheim	Forchheim
Germany	Klinikum Frankfurt (Oder) GmbH	Frankfurt
Germany	Gemeinschaftspraxis - Freiburg	Freiburg
Germany	Klinikum Garmisch - Partenkirchen GmbH	Garmisch-Partenkirchen
Germany	Internistische Praxis - Gerlingen	Gerlingen
Germany	Internistische Praxisgemeinschaft	Germering
Germany	Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie	Giessen
Germany	Klinik fuer Radioonkologie und Strahlentherapie	Goeppingen
Germany	Universitaetsklinikum Goettingen	Goettingen
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Praxis fuer Haematologie und Internistische Onkologie - Greifswald	Greifswald
Germany	Internistisch-Haematologische Gemeinschaftspraxis - Gustrow	Gustrow
Germany	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH	Hagen
Germany	Internistische Gemeinschaftspraxis - Halle	Halle
Germany	Internistische Praxis - Halle	Halle
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Evangelische Krankenhaus Hamm	Hamm
Germany	St. Marien-Hospital Hamm - Klinik Knappenstrasse	Hamm
Germany	Schwerpunktpraxis Haematologie/Onkologie - Hannover	Hannover
Germany	Universitaets-Kinderklinik Heidelberg	Heidelberg
Germany	SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen	Heilbronn
Germany	Privatklinik Dr. R. Schindlbeck GmbH & Co. KG	Herrsching
Germany	Onkologische Schwerpunktpraxis	Hildesheim
Germany	Onkologische Gemeinschaftspraxis - Hoevelhof	Hoevelhof
Germany	Evang. Hospital	Holzminden
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Clinic for Bone Marrow Transplantation and Hematology and Oncology	Idar-Oberstein
Germany	Internistische Praxis - Ingolstadt	Ingolstadt
Germany	Internistische Gemeinschaftspraxis - Jena	Jena
Germany	Onkologische Gemeinschaftspraxis - Kaiserslautern	Kaiserslautern
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	St. Vincentius-Kliniken	Karlsruhe
Germany	Staedtisches Klinikum Karlsruhe gGmbH	Karlsruhe
Germany	Internistische Gemeinschaftspraxis - Kassel	Kassel
Germany	Klinikum Kempten Oberallgaeu	Kempten
Germany	University Hospital Schleswig-Holstein - Kiel Campus	Kiel
Germany	Praxis Fuer Haematologie Internistische Onkologie	Koeln
Germany	Internistische Onkologische Praxis - Kronach	Kronach
Germany	Internistische Praxis - Landshut	Landshut
Germany	Onkologische Schwerpunktpraxis - Leer	Leer
Germany	Klinikum Lippe - Lemgo	Lemgo
Germany	Internistische Praxis - Ludwigsburg	Ludwigsburg
Germany	Staedtisches Klinikum Magdeburg - Altstadt	Magdeburg
Germany	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg
Germany	III Medizinische Klinik Mannheim	Mannheim
Germany	Haematologische Praxis - Moenchengladbach	Moenchengladbach
Germany	Hamatologie/Onkologie Praxisgemeinschaft - Muenchen	Muenchen
Germany	University of Muenster	Muenster
Germany	Internistische Praxis - Muhr am See	Muhr am See
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum der Universitaet Muenchen - Innenstadt Campus	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Krankenhaus Muenchen Schwabing	Munich
Germany	Munich Oncologic Practice at Elisenhof	Munich
Germany	Onkologische Schwerpunktpraxis Dr. Schmidt	Neunkirchen
Germany	Praxis fuer Haematologie und Interne Onkologie	Norderstedt
Germany	Sudharz-Krankenhaus Nordhausen gGmbH	Nordhausen
Germany	Klinikum Nuernberg - Klinikum Nord	Nuernberg
Germany	Internistische Gemeinschaftspraxis - Offenbach	Offenbach
Germany	Internistische Gemeinschaftspraxis - Oldenburg	Oldenburg
Germany	Paracelsus Karankenhaus Ruit	Ostfildern
Germany	Asklepios Klinik Pasewalk	Pasewalk
Germany	Vogtland - Klinikum Plauen GMBH	Plauen
Germany	Klinikum Ernst Von Bergmann	Postdam
Germany	Internistische Gemeinschaftspraxis - Potsdam	Potsdam
Germany	Krankenhaus Barmherzige Brueder Regensburg	Regensburg
Germany	Staedtische Klinikum-Kinderklinik	Rosenheim
Germany	Haematologische/Onkologische Schwerpunktpraxis - Rostock	Rostock
Germany	Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock	Rostock
Germany	Caritasklinik St. Theresia	Saarbrucken
Germany	Schwerpunktpraxis fuer Haematologie und Onkologie	Saarbruecke
Germany	Klinikum Schwerin	Schwerin
Germany	St. Marien - Krankenhaus Siegen GMBH	Siegen
Germany	Diakonie Klinikum Stuttgart	Stuttgart
Germany	Haematologische Praxis	Stuttgart
Germany	Internistische Gemeinschaftspraxis - Stuttgart	Stuttgart
Germany	Klinik fuer Onkologie - Katharinenhospital Stuttgart	Stuttgart
Germany	Marienhospital Stuttgart	Stuttgart
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	Krankenanstalt Mutterhaus der Borromaerinnen	Trier
Germany	Onkologische Gemeinschaftspraxis - Trier	Trier
Germany	Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie	Tuebingen
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Germany	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm
Germany	St. Marienhospital - Vechta	Vechta
Germany	Haematologisch-Onkologische Schwerpunktpraxis - Weilheim	Weilheim
Germany	Internistische Praxis - Wendlingen	Wendlingen
Germany	Gemeinschaftspraxis	Worms
Germany	Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg	Wuerzburg
Germany	Kliniken St. Antonius	Wuppertal 2
Germany	Hamatologisch - Onkologische Praxis Wurzburg	Wurzburg
Germany	Internistische Praxis - Zittau	Zittau

Sponsors (1)

Lead Sponsor	Collaborator
German CLL Study Group

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (7)

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. — View Citation

Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, Siehl S, Jäger U, Bergmann M, Stilgenbauer S, Schweighofer C, Wendtner CM, Döhner H, Brittinger G, Emmerich B, Hallek M; German CLL Study Group. Fludarabine plus cyclophosphamide vers — View Citation

Eichhorst BF, Busch R, Obwandner T, Kuhn-Hallek I, Herschbach P, Hallek M; German CLL Study Group. Health-related quality of life in younger patients with chronic lymphocytic leukemia treated with fludarabine plus cyclophosphamide or fludarabine alone for — View Citation

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. — View Citation

Goede V, Cramer P, Busch R, Bergmann M, Stauch M, Hopfinger G, Stilgenbauer S, Döhner 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. — View Citation

Jebaraj BMC, Tausch E, Landau DA, Bahlo J, Robrecht S, Taylor-Weiner AN, Bloehdorn J, Scheffold A, Mertens D, Böttcher S, Kneba M, Jäger U, Zenz T, Wenger MK, Fingerle-Rowson G, Wendtner C, Fink AM, Wu CJ, Eichhorst B, Fischer K, Hallek M, Döhner H, Stilgenbauer S. Short telomeres are associated with inferior outcome, genomic complexity, and clonal evolution in chronic lymphocytic leukemia. Leukemia. 2019 Mar 25. doi: 10.1038/s41375-019-0446-4. [Epub ahead of print] — View Citation

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	Progression-free survival	date of randomization until progression of disease or death of any cause	18 Month after end of treatment of the last patient
Primary	Overall survival	Date of randomization until date of death	18 Month after end of treatment of the last patient
Primary	Duration of remission	Clinical response was defined according to the guidelines of the NCI-sponsored workshop	18 Month after end of treatment of the last patient
Secondary	Incidence of side effects	Toxic effects of treatment were evaluated according to the Common Toxicity Criteria (CTC 1.0)	up to 28 days after the last dose of study medication
Secondary	Quality of life	EORTC QUOL Questionnaire	18 Month after end of treatment of the last patient

External Links

•   Click here for more information about this study: CLL4 (German CLL Study Group)