Clinical trial NCT00262782: Fludarabine or Observation in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia
Official title: Prognostic Factors and Risk-Adapted Therapy in Patients With Early Stage Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: B-cell chronic lymphocytic leukemia
stage 0 chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
Lead sponsor: German CLL Study Group
Sponsor class: OTHER
First posted: 2005-12-07
Enrollment: 877
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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, 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 fludarabine is more effective than observation in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying fludarabine to see how well it works compared to observation only in treating patients with stage 0, stage I, or stage II B-cell chronic lymphocytic leukemia.

Detailed description: OBJECTIVES:

* Identify prognostic factors that predict a short survival in patients with stage 0-II B-cell chronic lymphocytic leukemia treated with fludarabine or observation only.

OUTLINE: This is a randomized study. Patients are stratified according to risk (high risk vs low risk). Patients in the low-risk group undergo observation only. Patients in the high-risk group are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive fludarabine.
* Arm II: Patients undergo observation only.

PROJECTED ACCRUAL: A total of 880 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Confirmed diagnosis of B-cell chronic lymphocytic leukemia

  * Rai stage 0-II (Binet stage A) disease
* Meets 1 of the following criteria:

  * High-risk disease, as defined by the following:

    * Serum thymidine kinase level \> 7.0 U/L
    * Elevated β2-microglobulin level
    * Presence of non-nodular bone marrow infiltration
    * Short lymphocyte doubling time
  * Low-risk disease

    * Meets none of the criteria (as listed above) for high-risk disease

PATIENT CHARACTERISTICS:

Performance status

* Not specified

Life expectancy

* More than 6 months

Hematopoietic

* No autoimmune hemolytic anemia
* No thrombocytopenia

Hepatic

* Not specified

Renal

* Not specified

Other

* No severe organ dysfunction
* No other prior or concurrent malignancy

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: Wien
country: Austria
facility: Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik
city: Amberg
country: Germany
facility: Klinikum St. Marien
city: Arnstadt
country: Germany
facility: Internistische Praxis - Arnstadt
city: Augsburg
country: Germany
facility: Zentralklinikum Augsburg
city: Aurich
country: Germany
facility: Kreiskrankenhaus Aurich
city: Bad Friedrichshall
country: Germany
facility: Regional Hospital Am Plattenwald
city: Bad Hersfeld
country: Germany
facility: Regional Hospital Bad Hersfeld
city: Bad Reichenhall
country: Germany
facility: Arzt fuer Innere Medizin - Bad Reichenhall
city: Bad Saarow
country: Germany
facility: Humaine - Clinic
city: Bad Urach
country: Germany
facility: Ermstalklinik Bad Urach
city: Berlin
country: Germany
facility: Internistische Praxis - Berlin
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Haematologisch-Onkologische Schwerpunktpraxis
city: Berlin
country: Germany
facility: Internistische Praxis - Berlin
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charite - Campus Virchow Klinikum
city: Betzdorf
country: Germany
facility: Gemeinschaftspraxis - Betzdorf
city: Bremen
country: Germany
facility: Praxis Dres. F.& G. Doering
city: Burglengenfeld
country: Germany
facility: Krankenhaus Burglengenfeld
city: Cottbus
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Dessau
country: Germany
facility: Staedtisches Klinikum Dessau
city: Dresden
country: Germany
facility: Onkologische Gemeinschaftspraxis - Dresden
city: Duesseldorf
country: Germany
facility: Universitaetsklinik Duesseldorf
city: Duisburg
country: Germany
facility: Michael Schaefers und Partner
city: Ehingen
country: Germany
facility: Internistische Gemeinschaftpraxis - Ehingen
city: Erding
country: Germany
facility: Onkologische Schwerpunktpraxis - Erding
city: Erfurt
country: Germany
facility: Internistische/Onkologische Praxis - 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: Esslingen
country: Germany
facility: Staedtische Kliniken Esslingen
city: Forchheim
country: Germany
facility: Internistische Gemeinschaftspraxis - Forchheim
city: Garmisch-Partenkirchen
country: Germany
facility: Klinikum Garmisch - Partenkirchen
city: Germering
country: Germany
facility: Gemeinschaftspraxis - Germering
city: Germering
country: Germany
facility: Internistische Praxisgemeinschaft
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Gross-Gerau
country: Germany
facility: Onkologische Gemeinschaftspraxis - Gross-Gerau
city: Hagen
country: Germany
facility: St. Marien Hospital at Katholisches Krankenhaus hagen gem. GmbH
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Halle
country: Germany
facility: Internistische Praxis - Halle
city: Halle
country: Germany
facility: Internistische Gemeinschaftspraxis - Halle
city: Halle
country: Germany
facility: Martin Luther Universitaet
city: Hamburg
country: Germany
facility: Praxis fur Innere Medizin - Hamburg
city: Hamburg
country: Germany
facility: Allgemeines Krankenhaus St. Georg
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Schwerpunktpraxis Haematologie/Onkologie - Hannover
city: Hausham
country: Germany
facility: Facharzt fuer Allgemeinmedizin - Hausham
city: Hechingen
country: Germany
facility: Facharzt fuer Innere Medizin - Hechingen
city: Heidelberg
country: Germany
facility: Onkologische Schwerpunktpraxis Heidelberg
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
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: Iserlohn
country: Germany
facility: Praxis am Evangelischen Krankenhaus Bethanien
city: Jena
country: Germany
facility: Internistische Gemeinschaftspraxis - Jena
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Karlsruhe
country: Germany
facility: Staedt Klinikum Karlsruhe GGMBH
city: Karlsruhe
country: Germany
facility: Facharzt Fuer Jnnere Medizin
city: Karlsruhe
country: Germany
facility: St. Vincentius-Kliniken
city: Kassel
country: Germany
facility: Internistische Gemeinschaftspraxis - Kassel
city: Kiel
country: Germany
facility: Staedtische Krankenhaus Kiel
city: Koeln
country: Germany
facility: Praxis Fuer Haematologie Internistische Onkologie
city: Koln
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
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: Magdeburg
country: Germany
facility: Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
city: Mannheim
country: Germany
facility: Gemeinschaftspraxis
city: Marburg
country: Germany
facility: Philipps-Universitaet Marburg Klinikum
city: Memmingen
country: Germany
facility: Internistische Gemeinschaftspraxis - Memmingen
city: Minden
country: Germany
facility: Klinikum Minden
city: Moenchengladbach
country: Germany
facility: Haematologische Praxis - Moenchengladbach
city: Muenster
country: Germany
facility: Haematologisch-onkologische Gemeinschaftspraxis - Muenster
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: Murnau
country: Germany
facility: Klinikum Garmisch-Partenkirchen GmbH Abteilung fuer Innere Medizin Murnau
city: Neuenkirchen
country: Germany
facility: Internistische Praxis - Neuenkirchen
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: Hematologische Praxis
city: Osnabrueck
country: Germany
facility: Gemeinschaftliche Schwerpunktpraxis - Osnabrueck
city: Pforzheim
country: Germany
facility: Municipal Hospital Complex
city: Regensburg
country: Germany
facility: Hematologische Onkologische Praxis
city: Rheine
country: Germany
facility: Jakobi Krankenhaus
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: Schrobenhausen
country: Germany
facility: Onkologische Schwerpunktpraxis - Schrobenhausen
city: Schwenningen
country: Germany
facility: Praxis - Schwenningen
city: Siegen
country: Germany
facility: St. Marien - Krankenhaus Siegen GMBH
city: Siegen
country: Germany
facility: Evang. Jung-Stilling Hospital
city: Stade
country: Germany
facility: Praxisgemeinschaft - Stade
city: Straubing
country: Germany
facility: Onkologische Schwerpunktpraxis - Straubing
city: Stuttgart
country: Germany
facility: Haematologische Praxis
city: Stuttgart
country: Germany
facility: Diakonie Klinikum Stuttgart
city: Trier
country: Germany
facility: Onkologische Gemeinschaftspraxis - Trier
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: Weiden
country: Germany
facility: Gemeinschaftspraxis - Weiden
city: Weilheim
country: Germany
facility: Haematologisch-Onkologische Schwerpunktpraxis - Weilheim
city: Wendlingen
country: Germany
facility: Internistische Praxis - Wendlingen
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
Study officials:
affiliation: Medizinische Universitaetsklinik I at the University of Cologne
name: Michael Hallek, MD
role: STUDY_CHAIR
References:
citation: Gobel M, Eisele L, Mollmann M, Huttmann A, Johansson P, Scholtysik R, Bergmann M, Busch R, Dohner H, Hallek M, Seiler T, Stilgenbauer S, Klein-Hitpass L, Duhrsen U, Durig J. Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. PLoS One. 2013 Aug 23;8(8):e72107. doi: 10.1371/journal.pone.0072107. eCollection 2013.
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: Bergmann MA, Eichhorst BF, Busch R, et al.: Early and risk-adapted therapy with fludarabine in high-risk Binet stage A CLL patients prolongs progression free survival but not overall survival: results of the CLL1 protocol of the German CLL Study Group (GCLLSG). [Abstract] Blood 110 (11): A-2038, 2007.
citation: Bergmann MA, Eichhorst BF, Busch R, et al.: Prospective evaluation of prognostic parameters in early stage chronic lymphocytic leukemia (CLL): results of the CLL1-protocol of the German CLL Study Group (GCLLSG). [Abstract] Blood 110 (11): A-625, 2007.
citation: Hoechstetter MA, Busch R, Eichhorst B, Buhler A, Winkler D, Eckart MJ, Vehling-Kaiser U, Schimke H, Jager U, Hurtz HJ, Hopfinger G, Hartmann F, Fuss H, Abenhardt W, Blau I, Freier W, Muller L, Goebeler M, Wendtner CM, Bahlo J, Fischer K, Bentz M, Emmerich B, Dohner H, Hallek M, Stilgenbauer S. Early, risk-adapted treatment with fludarabine in Binet stage A chronic lymphocytic leukemia patients: results of the CLL1 trial of the German CLL study group. Leukemia. 2017 Dec;31(12):2833-2837. doi: 10.1038/leu.2017.246. Epub 2017 Aug 14. No abstract available.
citation: Hoechstetter MA, Busch R, Eichhorst B, Buhler A, Winkler D, Bahlo J, Robrecht S, Eckart MJ, Vehling-Kaiser U, Jacobs G, Jager U, Hurtz HJ, Hopfinger G, Hartmann F, Fuss H, Abenhardt W, Blau I, Freier W, Muller L, Goebeler M, Wendtner C, Fischer K, Herling CD, Starck M, Bentz M, Emmerich B, Dohner H, Stilgenbauer S, Hallek M. Prognostic model for newly diagnosed CLL patients in Binet stage A: results of the multicenter, prospective CLL1 trial of the German CLL study group. Leukemia. 2020 Apr;34(4):1038-1051. doi: 10.1038/s41375-020-0727-y. Epub 2020 Feb 10.
citation: Jaramillo S, Agathangelidis A, Schneider C, Bahlo J, Robrecht S, Tausch E, Bloehdorn J, Hoechstetter M, Fischer K, Eichhorst B, Goede V, Hallek M, Dohner H, Rosenquist R, Ghia P, Stamatopoulos K, Stilgenbauer S. Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG). Haematologica. 2020 Nov 1;105(11):2598-2607. doi: 10.3324/haematol.2019.231027.
citation: Kreuzberger N, Damen JA, Trivella M, Estcourt LJ, Aldin A, Umlauff L, Vazquez-Montes MD, Wolff R, Moons KG, Monsef I, Foroutan F, Kreuzer KA, Skoetz N. Prognostic models for newly-diagnosed chronic lymphocytic leukaemia in adults: a systematic review and meta-analysis. Cochrane Database Syst Rev. 2020 Jul 31;7(7):CD012022. doi: 10.1002/14651858.CD012022.pub2.
citation: Pflug N, Bahlo J, Shanafelt TD, Eichhorst BF, Bergmann MA, Elter T, Bauer K, Malchau G, Rabe KG, Stilgenbauer S, Dohner H, Jager U, Eckart MJ, Hopfinger G, Busch R, Fink AM, Wendtner CM, Fischer K, Kay NE, Hallek M. Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood. 2014 Jul 3;124(1):49-62. doi: 10.1182/blood-2014-02-556399. Epub 2014 May 5.