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Chronic Lymphocytic LeukemiaPhase 3NCT00276848

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

A Phase 3 study testing Fludarabine plus Cyclophosphamide and Fludarabine in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 135 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Fludarabine plus Cyclophosphamide and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
375 participants
Where
135 sitesin 2 countries
Study dates
Jul 1999to Jul 2007
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

135 sites in 2 countries.

135 sites in 2 countries

Germany133 sites

  • Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie

    Ansbach, D-91522

  • Internistische Praxis - Arnstadt

    Arnstadt, D-99310

  • Specialist Practice for Oncology

    Aschaffenburg, D-63739

  • Klinikum Augsburg

    Augsburg, D-86156

  • Kreiskrankenhaus Aurich

    Aurich, D-26603

  • Kreiskrankenhaus

    Bad Hersfeld, D-36251

  • Caritas-Krankenhaus Bad Mergentheim

    Bad Mergentheim, D-97980

  • Humaine - Clinic

    Bad Saarow, D-15526

  • Internistische Praxis - Bad Salzuflen

    Bad Salzuflen, D-32105

  • Internistische Praxis - Bayreuth

    Bayreuth, D-95448

  • Internistische Gemeinschaftspraxis - Bergisch Gladbach

    Bergisch Gladbach, D-51429

  • Charite - Campus Charite Mitte

    Berlin, D-10117

  • Onkolog - Haematolog Schwerpunktpraxis

    Berlin, D-10559

  • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

    Berlin, D-12200

  • Onkologische Gemeinschaftspraxis - Berlin

    Berlin, D-13055

  • Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch

    Berlin, D-13122

  • Internistische Gemeinschaftspraxis - Berlin

    Berlin, D-13347

  • Charite - Campus Virchow Klinikum

    Berlin, D-13353

  • Evang. Waldkrankenhaus Spandau

    Berlin, D-13589

  • Internistische Praxis - Berlin

    Berlin, D-14052

  • Internistische Gemeinschaftspraxis - Berlin

    Berlin, D-14195

  • Krankenhaus Bietigheim

    Bietigheim, D-74321

  • DIAKO Ev. Diakonie Krankenhaus gGmbH

    Bremen, D-28239

  • Internistische Praxis - Chemnitz

    Chemnitz, D-09119

  • Praxis Fuer Haematologie Internistische Onkologie

    Cologne, D-50677

  • Medizinische Universitaetsklinik I at the University of Cologne

    Cologne, D-50924

  • Onkologische Schwerpunktpraxis

    Cottbus, D-03046

  • Onkologische Gemeinschaftspraxis - Dresden

    Dresden, D-01127

  • Krankenhaus Benrath

    Düsseldorf, D-40593

  • St. Georg Klinikum Eisenach GmbH

    Eisenach, D-99817

  • Hans - Susemihl - Krankenhaus

    Emden, D-26721

  • Internistische/Onkologische Praxis - Erfurt

    Erfurt, D-99084

  • Praxis DR. J. Weniger

    Erfurt, D-99085

  • Klinikum Erfurt

    Erfurt, D-99089

  • Praxis fuer Haematologie/Onkologie - Erfurt

    Erfurt, D-99094

  • Onkologische Schwerpunkt Praxis

    Erlangen, D-91052

  • St. Antonius Hospital

    Eschweiler, D-52249

  • Universitaetsklinikum Essen

    Essen, D-45122

  • Onkologische Praxis - Essen

    Essen, D-45136

  • Evangelisches Krankenhaus Essen Werden

    Essen, D-45239

  • Staedtische Kliniken Esslingen

    Esslingen am Neckar, D-73730

  • Internistische Gemeinschaftspraxis - Forchheim

    Forchheim, D-91301

  • Klinikum Frankfurt (Oder) GmbH

    Frankfurt, D-15236

  • Gemeinschaftspraxis - Freiburg

    Freiburg im Breisgau, D-79098

  • Klinikum Garmisch - Partenkirchen GmbH

    Garmisch-Partenkirchen, D-82467

  • Internistische Praxis - Gerlingen

    Gerlingen, D-70839

  • Internistische Praxisgemeinschaft

    Germering, D-82110

  • Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie

    Giessen, D-35392

  • Klinik fuer Radioonkologie und Strahlentherapie

    Göppingen, D-73035

  • Universitaetsklinikum Goettingen

    Göttingen, D-37075

  • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet

    Greifswald, D-17487

  • Praxis fuer Haematologie und Internistische Onkologie - Greifswald

    Greifswald, D-17489

  • Internistisch-Haematologische Gemeinschaftspraxis - Gustrow

    Güstrow, D-18273

  • St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

    Hagen, D-58095

  • Internistische Praxis - Halle

    Halle, D-06108

  • Internistische Gemeinschaftspraxis - Halle

    Halle, D-06110

  • Asklepios Klinik St. Georg

    Hamburg, D-20099

  • Universitaetsklinikum Hamburg-Eppendorf

    Hamburg, D-20246

  • Evangelische Krankenhaus Hamm

    Hamm, D-59063

  • St. Marien-Hospital Hamm - Klinik Knappenstrasse

    Hamm, D-59071

  • Schwerpunktpraxis Haematologie/Onkologie - Hannover

    Hanover, D-30169

  • Universitaets-Kinderklinik Heidelberg

    Heidelberg, D-69120

  • SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen

    Heilbronn, D-74064

  • Privatklinik Dr. R. Schindlbeck GmbH & Co. KG

    Herrsching am Ammersee, D-82211

  • Onkologische Schwerpunktpraxis

    Hildesheim, D-31134

  • Evang. Hospital

    Holzminden, D-37603

  • Universitaetsklinikum des Saarlandes

    Homburg, D-66421

  • Onkologische Gemeinschaftspraxis - Hoevelhof

    Hövelhof, D-33161

  • Clinic for Bone Marrow Transplantation and Hematology and Oncology

    Idar-Oberstein, D-55743

  • Internistische Praxis - Ingolstadt

    Ingolstadt, D-85049

  • Internistische Gemeinschaftspraxis - Jena

    Jena, D-07743

  • Westpfalz-Klinikum GmbH

    Kaiserslautern, D-67653

  • Onkologische Gemeinschaftspraxis - Kaiserslautern

    Kaiserslautern, D-67655

  • Staedtisches Klinikum Karlsruhe gGmbH

    Karlsruhe, D-76133

  • St. Vincentius-Kliniken

    Karlsruhe, D-76137

  • Internistische Gemeinschaftspraxis - Kassel

    Kassel, D-34117

  • Klinikum Kempten Oberallgaeu

    Kempten, D-87439

  • University Hospital Schleswig-Holstein - Kiel Campus

    Kiel, D-24105

  • Internistische Onkologische Praxis - Kronach

    Kronach, D-96317

  • Internistische Praxis - Landshut

    Landshut, D-84028

  • Onkologische Schwerpunktpraxis - Leer

    Leer, D-26789

  • Klinikum Lippe - Lemgo

    Lemgo, D-32657

  • Internistische Praxis - Ludwigsburg

    Ludwigsburg, D-71638

  • Staedtisches Klinikum Magdeburg - Altstadt

    Magdeburg, D-39104

  • Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

    Magdeburg, D-39120

  • III Medizinische Klinik Mannheim

    Mannheim, D-68305

  • Haematologische Praxis - Moenchengladbach

    Mönchengladbach, D-41239

  • Internistische Praxis - Muhr am See

    Muhr am See, D-91735

  • Hamatologie/Onkologie Praxisgemeinschaft - Muenchen

    München, D-81245

  • Klinikum der Universitaet Muenchen - Innenstadt Campus

    Munich, D-80331

  • Munich Oncologic Practice at Elisenhof

    Munich, D-80335

  • Krankenhaus Muenchen Schwabing

    Munich, D-80804

  • Klinikum der Universitaet Muenchen - Grosshadern Campus

    Munich, D-81377

  • Klinikum Rechts Der Isar - Technische Universitaet Muenchen

    Munich, D-81675

  • University of Muenster

    Münster, D-48129

  • Onkologische Schwerpunktpraxis Dr. Schmidt

    Neunkirchen, D-66538

  • Praxis fuer Haematologie und Interne Onkologie

    Norderstedt, D-22844

  • Sudharz-Krankenhaus Nordhausen gGmbH

    Nordhausen, D-99734

  • Klinikum Nuernberg - Klinikum Nord

    Nuremberg, D-90419

  • Internistische Gemeinschaftspraxis - Offenbach

    Offenbach, D-63065

  • Internistische Gemeinschaftspraxis - Oldenburg

    Oldenburg, D-26121

  • Paracelsus Karankenhaus Ruit

    Ostfildern, D-73760

  • Asklepios Klinik Pasewalk

    Pasewalk, D-17309

  • Vogtland - Klinikum Plauen GMBH

    Plauen, D-08529

  • Klinikum Ernst Von Bergmann

    Postdam, D-14467

  • Internistische Gemeinschaftspraxis - Potsdam

    Potsdam, D-14467

  • Krankenhaus Barmherzige Brueder Regensburg

    Regensburg, D-93049

  • Staedtische Klinikum-Kinderklinik

    Rosenheim, D-83022

  • Haematologische/Onkologische Schwerpunktpraxis - Rostock

    Rostock, D-18057

  • Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock

    Rostock, D-18057

  • Caritasklinik St. Theresia

    Saarbrücken, D-66113

  • Schwerpunktpraxis fuer Haematologie und Onkologie

    Saarbruecke, D-66113

  • Klinikum Schwerin

    Schwerin, D-19049

  • St. Marien - Krankenhaus Siegen GMBH

    Siegen, D-57072

  • Haematologische Praxis

    Stuttgart, D-70173

  • Klinik fuer Onkologie - Katharinenhospital Stuttgart

    Stuttgart, D-70174

  • Diakonie Klinikum Stuttgart

    Stuttgart, D-70176

  • Internistische Gemeinschaftspraxis - Stuttgart

    Stuttgart, D-70176

  • Marienhospital Stuttgart

    Stuttgart, D-70199

  • Robert-Bosch-Krankenhaus

    Stuttgart, D-70376

  • Krankenanstalt Mutterhaus der Borromaerinnen

    Trier, D-54290

  • Onkologische Gemeinschaftspraxis - Trier

    Trier, D-54290

  • Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie

    Tübingen, D-72070

  • Southwest German Cancer Center at Eberhard-Karls-University

    Tübingen, D-72076

  • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

    Ulm, D-89081

  • St. Marienhospital - Vechta

    Vechta, D-49377

  • Haematologisch-Onkologische Schwerpunktpraxis - Weilheim

    Weilheim, D-82362

  • Internistische Praxis - Wendlingen

    Wendlingen, D-73240

  • Gemeinschaftspraxis

    Worms, D-67547

  • Kliniken St. Antonius

    Wuppertal, D-42283

  • Hamatologisch - Onkologische Praxis Wurzburg

    Würzburg, D-97070

  • Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg

    Würzburg, D-97070

  • Internistische Praxis - Zittau

    Zittau, D-02763

Other trials in Germany

Austria2 sites

  • Allgemeines Krankenhaus - Universitatskliniken

    Vienna, A-1090

  • Hanuschkrankenhaus

    Vienna, A-1140

Other trials in Austria

About this study

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

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.

Read the 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.

Being tested
Fludarabine plus Cyclophosphamide, Fludarabine
Keywords
stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fludarabine plus CyclophosphamideDrug

    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

  • FludarabineDrug

    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

Study groups in NCT00276848
Study groupRoleWhat they receive
Fludarabine plus CyclophosphamideActive comparatorNot described
Receives: Drug: Fludarabine plus Cyclophosphamide
FludarabineActive comparatorNot described
Receives: Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival

    date of randomization until progression of disease or death of any cause

    Measured: 18 Month after end of treatment of the last patient

  2. Overall survival

    Date of randomization until date of death

    Measured: 18 Month after end of treatment of the last patient

  3. Duration of remission

    Clinical response was defined according to the guidelines of the NCI-sponsored workshop

    Measured: 18 Month after end of treatment of the last patient

Secondary outcomes (2)

  1. Incidence of side effects

    Toxic effects of treatment were evaluated according to the Common Toxicity Criteria (CTC 1.0)

    Measured: up to 28 days after the last dose of study medication

  2. Quality of life

    EORTC QUOL Questionnaire

    Measured: 18 Month after end of treatment of the last patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2006 (estimated)
  2. Study startJul 1999
  3. Primary completionJul 2003
  4. Study completionJul 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
375 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00276848
Sponsor's protocol ID
CLL4
Other IDs
EU-20538, GCLLSG-153, ISRCTN75653261, MEDAC-GCLLSG-CLL4, CDR0000455094
Status last verified
May 2019
First submitted
12 Jan 2006
Last updated
23 May 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 21139079

  • 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.

    PubMed 24412156

  • 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.

    PubMed 24584349

  • 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.

    PubMed 30911113

  • 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.

    PubMed 31092457

  • 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.

    PubMed 17389338

  • 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.

    PubMed 16219797

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fludarabine plus Cyclophosphamide and Fludarabine in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 135 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 135 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (time frame: 18 Month after end of treatment of the last patient). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00276848, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2019.

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