Clinical trial NCT00262795: Fludarabine or Chlorambucil as First-Line Therapy in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia
Official title: Fludarabine Versus Chlorambucil in First Line Therapy of Elderly Patients (More Than 65 Years) With Advanced Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: stage 0 chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
Lead sponsor: German CLL Study Group
Sponsor class: OTHER
First posted: 2005-12-07
Enrollment: 206
Sex: ALL
Minimum age (years): 65
Maximum age (years): 79
Standard ages: 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 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Hanuschkrankenhaus
city: Amberg
country: Germany
facility: Klinikum St. Marien
city: Ansbach
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
city: Augsburg
country: Germany
facility: Zentralklinikum Augsburg
city: Bad Saarow
country: Germany
facility: Humaine - Clinic
city: Bayreuth
country: Germany
facility: Krankenhaus Hohe Warte Mediziniche Klinik
city: Berlin
country: Germany
facility: Onkologisches Versorgungszentrum Friedrichshain
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charite - Campus Virchow Klinikum
city: Bochum
country: Germany
facility: Saint Josef - Hospital Bochum
city: Bremen
country: Germany
facility: Praxis Dres. F.& G. Doering
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: Emden
country: Germany
facility: Hans - Susemihl - Krankenhaus
city: Erding
country: Germany
facility: Kreiskrankenhaus Erding
city: Erfurt
country: Germany
facility: Internistische/Onkologische Praxis - Erfurt
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Erlangen
country: Germany
facility: Onkologische Schwerpunkt Praxis
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Essen
country: Germany
facility: Evangelisches Krankenhaus Essen Werden
city: Freiburg
country: Germany
facility: Gemeinschaftspraxis - Freiburg
city: Garmisch-Partenkirchen
country: Germany
facility: Klinikum Garmisch - Partenkirchen
city: Gera
country: Germany
facility: Gemeinschaftspraxis Innere Medizin Hämatologie/Onkologie - Gera
city: Gerlingen
country: Germany
facility: Internistische Praxis - Gerlingen
city: Germering
country: Germany
facility: Internistische Praxisgemeinschaft
city: Goettingen
country: Germany
facility: Universitaetsklinikum Goettingen
city: Gustrow
country: Germany
facility: Internistisch-Haematologische Gemeinschaftspraxis - Gustrow
city: Halle
country: Germany
facility: Internistische Praxis - Halle
city: Halle
country: Germany
facility: Internistische Gemeinschaftspraxis - Halle
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Hamm
country: Germany
facility: St. Marien-Hospital Hamm - Klinik Knappenstrasse
city: Hannover
country: Germany
facility: Schwerpunktpraxis Haematologie/Onkologie - Hannover
city: Heiligenstadt
country: Germany
facility: Eichsfeld Klinikum gGmbH
city: Herrsching
country: Germany
facility: Medizinischen Klinik Dr. R. Schindlbeck
city: Hildesheim
country: Germany
facility: Oncological Specialist Practice
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Idar-Oberstein
country: Germany
facility: Clinic for Bone Marrow Transplantation and Hematology and Oncology
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Karlsruhe
country: Germany
facility: Staedt Klinikum Karlsruhe GGMBH
city: Kassel
country: Germany
facility: Internistische Gemeinschaftspraxis - Kassel
city: Kiel
country: Germany
facility: Staedtische Krankenhaus Kiel
city: Krefeld
country: Germany
facility: Krankenhaus Maria-Hilf Krefeld
city: Kronach
country: Germany
facility: Internistische Onkologische Praxis - Kronach
city: Landshut
country: Germany
facility: Internistische Praxis - Landshut
city: Lemgo
country: Germany
facility: Klinikum Lippe - Lemgo
city: Ludwigsburg
country: Germany
facility: Internistische Praxis - Ludwigsburg
city: Luedenscheid
country: Germany
facility: Kreiskrankenhaus Luedenscheid
city: Mannheim
country: Germany
facility: III Medizinische Klinik Mannheim
city: Muenster
country: Germany
facility: Haematologisch-onkologische Gemeinschaftspraxis - Muenster
city: Munchber
country: Germany
facility: Regional Hospital Munchberg
city: Munchen
country: Germany
facility: Hamatologie/Onkologie Praxisgemeinschaft - Munchen
city: Munich
country: Germany
facility: Klinikum Innenstadt
city: Munich
country: Germany
facility: Krankenhaus Muenchen Schwabing
city: Munich
country: Germany
facility: Hamatologische Schwerpunktpraxis
city: Munich
country: Germany
facility: Munich Oncologic Practice at Elisenhof
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Staedtisches Krankenhaus Muenchen - Harlaching
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: Nuernberg
country: Germany
facility: Praxisklinik fuer Innere Medizin - Nuernberg
city: Nuernberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Oberstaufen
country: Germany
facility: Internistische Gemeinschaftspraxis - Oberstaufen
city: Offenbach
country: Germany
facility: Internistische Gemeinschaftspraxis - Offenbach
city: Oldenburg
country: Germany
facility: Internistische Gemeinschaftspraxis - Oldenburg
city: Postdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Rostock
country: Germany
facility: Haematologische/Onkologische Schwerpunktpraxis - Rostock
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
city: Russelsheim
country: Germany
facility: Internistische Schwerpunktpraxis
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresia
city: Saarbruecken
country: Germany
facility: Internistische Gemeinschaftspraxis - Saarbruecken
city: Saarbruecke
country: Germany
facility: Schwerpunktpraxis Fuer Haematologie Und Onkologie
city: Sigmaringen
country: Germany
facility: Kliniken Landkreis Sigmaringen GMBH
city: Stuttgart
country: Germany
facility: Internistische Gemeinschaftspraxis - Stuttgart
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart
city: Stuttgart
country: Germany
facility: Haematologische Praxis
city: Stuttgart
country: Germany
facility: Klinik fuer Onkologie - Katharinenhospital Stuttgart
city: Trier
country: Germany
facility: Onkologische Gemeinschaftspraxis - Trier
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromaerinnen
city: Tuebingen
country: Germany
facility: Southwest German Cancer Center at Eberhard-Karls-University
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Vechta
country: Germany
facility: St. Marien Hospital
city: Worms
country: Germany
facility: Gemeinschaftspraxis
city: Wuppertal 2
country: Germany
facility: Kliniken St. Antonius
city: Wurzburg
country: Germany
facility: Hamatologisch - Onkologische Praxis Wurzburg
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: 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, 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.