Clinical trial NCT00276848: Fludarabine With or Without Cyclophosphamide in Treating Patients With Advanced Chronic Lymphocytic Leukemia
Official title: Fludarabine Versus Fludarabine Plus Cyclophosphamide in First Line Therapy of Younger Patients (Up to 65 Years) With Advanced Chronic Lymphocytic Leukemia (CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
Lead sponsor: German CLL Study Group
Sponsor class: OTHER
First posted: 2006-01-13
Enrollment: 375
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival
timeFrame: 18 Month after end of treatment of the last patient
measure: Overall survival
timeFrame: 18 Month after end of treatment of the last patient
measure: Duration of remission
timeFrame: 18 Month after end of treatment of the last patient
Secondary outcomes:
measure: Incidence of side effects
timeFrame: up to 28 days after the last dose of study medication
measure: Quality of life
timeFrame: 18 Month after end of treatment of the last patient
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus - Universitatskliniken
city: Vienna
country: Austria
facility: Hanuschkrankenhaus
city: Ansbach
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
city: Arnstadt
country: Germany
facility: Internistische Praxis - Arnstadt
city: Aschaffenburg
country: Germany
facility: Specialist Practice for Oncology
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Aurich
country: Germany
facility: Kreiskrankenhaus Aurich
city: Bad Hersfeld
country: Germany
facility: Kreiskrankenhaus
city: Bad Mergentheim
country: Germany
facility: Caritas-Krankenhaus Bad Mergentheim
city: Bad Saarow
country: Germany
facility: Humaine - Clinic
city: Bad Salzuflen
country: Germany
facility: Internistische Praxis - Bad Salzuflen
city: Bayreuth
country: Germany
facility: Internistische Praxis - Bayreuth
city: Bergisch Gladbach
country: Germany
facility: Internistische Gemeinschaftspraxis - Bergisch Gladbach
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Onkolog - Haematolog Schwerpunktpraxis
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Onkologische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Charite - Campus Virchow Klinikum
city: Berlin
country: Germany
facility: Evang. Waldkrankenhaus Spandau
city: Berlin
country: Germany
facility: Internistische Praxis - Berlin
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Bietigheim
country: Germany
facility: Krankenhaus Bietigheim
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie Krankenhaus gGmbH
city: Chemnitz
country: Germany
facility: Internistische Praxis - Chemnitz
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Cottbus
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Dresden
country: Germany
facility: Onkologische Gemeinschaftspraxis - Dresden
city: Dusseldorf
country: Germany
facility: Krankenhaus Benrath
city: Eisenach
country: Germany
facility: St. Georg Klinikum Eisenach GmbH
city: Emden
country: Germany
facility: Hans - Susemihl - Krankenhaus
city: Erfurt
country: Germany
facility: Internistische/Onkologische Praxis - Erfurt
city: Erfurt
country: Germany
facility: Praxis DR. J. Weniger
city: Erfurt
country: Germany
facility: Klinikum Erfurt
city: Erfurt
country: Germany
facility: Praxis fuer Haematologie/Onkologie - Erfurt
city: Erlangen
country: Germany
facility: Onkologische Schwerpunkt Praxis
city: Eschweiler
country: Germany
facility: St. Antonius Hospital
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Essen
country: Germany
facility: Onkologische Praxis - Essen
city: Essen
country: Germany
facility: Evangelisches Krankenhaus Essen Werden
city: Esslingen
country: Germany
facility: Staedtische Kliniken Esslingen
city: Forchheim
country: Germany
facility: Internistische Gemeinschaftspraxis - Forchheim
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Freiburg
country: Germany
facility: Gemeinschaftspraxis - Freiburg
city: Garmisch-Partenkirchen
country: Germany
facility: Klinikum Garmisch - Partenkirchen GmbH
city: Gerlingen
country: Germany
facility: Internistische Praxis - Gerlingen
city: Germering
country: Germany
facility: Internistische Praxisgemeinschaft
city: Giessen
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
city: Goeppingen
country: Germany
facility: Klinik fuer Radioonkologie und Strahlentherapie
city: Goettingen
country: Germany
facility: Universitaetsklinikum Goettingen
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Greifswald
country: Germany
facility: Praxis fuer Haematologie und Internistische Onkologie - Greifswald
city: Gustrow
country: Germany
facility: Internistisch-Haematologische Gemeinschaftspraxis - Gustrow
city: Hagen
country: Germany
facility: St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
city: Halle
country: Germany
facility: Internistische Praxis - Halle
city: Halle
country: Germany
facility: Internistische Gemeinschaftspraxis - Halle
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Hamm
country: Germany
facility: Evangelische Krankenhaus Hamm
city: Hamm
country: Germany
facility: St. Marien-Hospital Hamm - Klinik Knappenstrasse
city: Hannover
country: Germany
facility: Schwerpunktpraxis Haematologie/Onkologie - Hannover
city: Heidelberg
country: Germany
facility: Universitaets-Kinderklinik Heidelberg
city: Heilbronn
country: Germany
facility: SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen
city: Herrsching
country: Germany
facility: Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
city: Hildesheim
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Hoevelhof
country: Germany
facility: Onkologische Gemeinschaftspraxis - Hoevelhof
city: Holzminden
country: Germany
facility: Evang. Hospital
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Idar-Oberstein
country: Germany
facility: Clinic for Bone Marrow Transplantation and Hematology and Oncology
city: Ingolstadt
country: Germany
facility: Internistische Praxis - Ingolstadt
city: Jena
country: Germany
facility: Internistische Gemeinschaftspraxis - Jena
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Kaiserslautern
country: Germany
facility: Onkologische Gemeinschaftspraxis - Kaiserslautern
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH
city: Karlsruhe
country: Germany
facility: St. Vincentius-Kliniken
city: Kassel
country: Germany
facility: Internistische Gemeinschaftspraxis - Kassel
city: Kempten
country: Germany
facility: Klinikum Kempten Oberallgaeu
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein - Kiel Campus
city: Koeln
country: Germany
facility: Praxis Fuer Haematologie Internistische Onkologie
city: Kronach
country: Germany
facility: Internistische Onkologische Praxis - Kronach
city: Landshut
country: Germany
facility: Internistische Praxis - Landshut
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis - Leer
city: Lemgo
country: Germany
facility: Klinikum Lippe - Lemgo
city: Ludwigsburg
country: Germany
facility: Internistische Praxis - Ludwigsburg
city: Magdeburg
country: Germany
facility: Staedtisches Klinikum Magdeburg - Altstadt
city: Magdeburg
country: Germany
facility: Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
city: Mannheim
country: Germany
facility: III Medizinische Klinik Mannheim
city: Moenchengladbach
country: Germany
facility: Haematologische Praxis - Moenchengladbach
city: Muenchen
country: Germany
facility: Hamatologie/Onkologie Praxisgemeinschaft - Muenchen
city: Muenster
country: Germany
facility: University of Muenster
city: Muhr am See
country: Germany
facility: Internistische Praxis - Muhr am See
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Innenstadt Campus
city: Munich
country: Germany
facility: Munich Oncologic Practice at Elisenhof
city: Munich
country: Germany
facility: Krankenhaus Muenchen Schwabing
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
city: Neunkirchen
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. Schmidt
city: Norderstedt
country: Germany
facility: Praxis fuer Haematologie und Interne Onkologie
city: Nordhausen
country: Germany
facility: Sudharz-Krankenhaus Nordhausen gGmbH
city: Nuernberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Offenbach
country: Germany
facility: Internistische Gemeinschaftspraxis - Offenbach
city: Oldenburg
country: Germany
facility: Internistische Gemeinschaftspraxis - Oldenburg
city: Ostfildern
country: Germany
facility: Paracelsus Karankenhaus Ruit
city: Pasewalk
country: Germany
facility: Asklepios Klinik Pasewalk
city: Plauen
country: Germany
facility: Vogtland - Klinikum Plauen GMBH
city: Postdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Potsdam
country: Germany
facility: Internistische Gemeinschaftspraxis - Potsdam
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brueder Regensburg
city: Rosenheim
country: Germany
facility: Staedtische Klinikum-Kinderklinik
city: Rostock
country: Germany
facility: Haematologische/Onkologische Schwerpunktpraxis - Rostock
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresia
city: Saarbruecke
country: Germany
facility: Schwerpunktpraxis fuer Haematologie und Onkologie
city: Schwerin
country: Germany
facility: Klinikum Schwerin
city: Siegen
country: Germany
facility: St. Marien - Krankenhaus Siegen GMBH
city: Stuttgart
country: Germany
facility: Haematologische Praxis
city: Stuttgart
country: Germany
facility: Klinik fuer Onkologie - Katharinenhospital Stuttgart
city: Stuttgart
country: Germany
facility: Diakonie Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Internistische Gemeinschaftspraxis - Stuttgart
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromaerinnen
city: Trier
country: Germany
facility: Onkologische Gemeinschaftspraxis - Trier
city: Tuebingen
country: Germany
facility: Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie
city: Tuebingen
country: Germany
facility: Southwest German Cancer Center at Eberhard-Karls-University
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
city: Vechta
country: Germany
facility: St. Marienhospital - Vechta
city: Weilheim
country: Germany
facility: Haematologisch-Onkologische Schwerpunktpraxis - Weilheim
city: Wendlingen
country: Germany
facility: Internistische Praxis - Wendlingen
city: Worms
country: Germany
facility: Gemeinschaftspraxis
city: Wuerzburg
country: Germany
facility: Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg
city: Wuppertal 2
country: Germany
facility: Kliniken St. Antonius
city: Wurzburg
country: Germany
facility: Hamatologisch - Onkologische Praxis Wurzburg
city: Zittau
country: Germany
facility: Internistische Praxis - Zittau
Study officials:
affiliation: Medizinische Universitaetsklinik I at the University of Cologne
name: Michael Hallek, MD
role: STUDY_CHAIR
References:
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.
citation: 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.
citation: 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.
citation: Jebaraj BMC, Tausch E, Landau DA, Bahlo J, Robrecht S, Taylor-Weiner AN, Bloehdorn J, Scheffold A, Mertens D, Bottcher S, Kneba M, Jager U, Zenz T, Wenger MK, Fingerle-Rowson G, Wendtner C, Fink AM, Wu CJ, Eichhorst B, Fischer K, Hallek M, Dohner H, Stilgenbauer S. Short telomeres are associated with inferior outcome, genomic complexity, and clonal evolution in chronic lymphocytic leukemia. Leukemia. 2019 Sep;33(9):2183-2194. doi: 10.1038/s41375-019-0446-4. Epub 2019 Mar 25.
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.
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 first-line therapy: a study by the German CLL Study Group. J Clin Oncol. 2007 May 1;25(13):1722-31. doi: 10.1200/JCO.2006.05.6929. Epub 2007 Mar 26.
citation: Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, Siehl S, Jager U, Bergmann M, Stilgenbauer S, Schweighofer C, Wendtner CM, Dohner H, Brittinger G, Emmerich B, Hallek M; German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006 Feb 1;107(3):885-91. doi: 10.1182/blood-2005-06-2395. Epub 2005 Oct 11.