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

May 21, 2019 updated by: German CLL Study Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

375

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, A-1090
        • Allgemeines Krankenhaus - Universitatskliniken
      • Vienna, Austria, A-1140
        • Hanuschkrankenhaus
  • Germany
      • Ansbach, Germany, D-91522
        • Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
      • Arnstadt, Germany, D-99310
        • Internistische Praxis - Arnstadt
      • Aschaffenburg, Germany, D-63739
        • Specialist Practice for Oncology
      • Augsburg, Germany, D-86156
        • Klinikum Augsburg
      • Aurich, Germany, D-26603
        • Kreiskrankenhaus Aurich
      • Bad Hersfeld, Germany, D-36251
        • Kreiskrankenhaus
      • Bad Mergentheim, Germany, D-97980
        • Caritas-Krankenhaus Bad Mergentheim
      • Bad Saarow, Germany, D-15526
        • Humaine - Clinic
      • Bad Salzuflen, Germany, D-32105
        • Internistische Praxis - Bad Salzuflen
      • Bayreuth, Germany, D-95448
        • Internistische Praxis - Bayreuth
      • Bergisch Gladbach, Germany, D-51429
        • Internistische Gemeinschaftspraxis - Bergisch Gladbach
      • Berlin, Germany, D-10117
        • Charité - Campus Charité Mitte
      • Berlin, Germany, D-12200
        • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
      • Berlin, Germany, D-13122
        • Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
      • Berlin, Germany, D-13353
        • Charité - Campus Virchow Klinikum
      • Berlin, Germany, D-10559
        • Onkolog - Haematolog Schwerpunktpraxis
      • Berlin, Germany, D-13055
        • Onkologische Gemeinschaftspraxis - Berlin
      • Berlin, Germany, D-13347
        • Internistische Gemeinschaftspraxis - Berlin
      • Berlin, Germany, D-13589
        • Evang. Waldkrankenhaus Spandau
      • Berlin, Germany, D-14052
        • Internistische Praxis - Berlin
      • Berlin, Germany, D-14195
        • Internistische Gemeinschaftspraxis - Berlin
      • Bietigheim, Germany, D-74321
        • Krankenhaus Bietigheim
      • Bremen, Germany, D-28239
        • DIAKO Ev. Diakonie Krankenhaus gGmbH
      • Chemnitz, Germany, D-09119
        • Internistische Praxis - Chemnitz
      • Cologne, Germany, D-50924
        • Medizinische Universitaetsklinik I at the University of Cologne
      • Cottbus, Germany, D-03046
        • Onkologische Schwerpunktpraxis
      • Dresden, Germany, D-01127
        • Onkologische Gemeinschaftspraxis - Dresden
      • Dusseldorf, Germany, D-40593
        • Krankenhaus Benrath
      • Eisenach, Germany, D-99817
        • St. Georg Klinikum Eisenach GmbH
      • Emden, Germany, D-26721
        • Hans - Susemihl - Krankenhaus
      • Erfurt, Germany, D-99085
        • Praxis DR. J. Weniger
      • Erfurt, Germany, D-99089
        • Klinikum Erfurt
      • Erfurt, Germany, D-99084
        • Internistische/Onkologische Praxis - Erfurt
      • Erfurt, Germany, D-99094
        • Praxis fuer Haematologie/Onkologie - Erfurt
      • Erlangen, Germany, D-91052
        • Onkologische Schwerpunkt Praxis
      • Eschweiler, Germany, D-52249
        • St. Antonius Hospital
      • Essen, Germany, D-45122
        • Universitaetsklinikum Essen
      • Essen, Germany, D-45239
        • Evangelisches Krankenhaus Essen Werden
      • Essen, Germany, D-45136
        • Onkologische Praxis - Essen
      • Esslingen, Germany, D-73730
        • Staedtische Kliniken Esslingen
      • Forchheim, Germany, D-91301
        • Internistische Gemeinschaftspraxis - Forchheim
      • Frankfurt, Germany, D-15236
        • Klinikum Frankfurt (Oder) GmbH
      • Freiburg, Germany, D-79098
        • Gemeinschaftspraxis - Freiburg
      • Garmisch-Partenkirchen, Germany, D-82467
        • Klinikum Garmisch - Partenkirchen GmbH
      • Gerlingen, Germany, D-70839
        • Internistische Praxis - Gerlingen
      • Germering, Germany, D-82110
        • Internistische Praxisgemeinschaft
      • Giessen, Germany, D-35392
        • Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
      • Goeppingen, Germany, D-73035
        • Klinik fuer Radioonkologie und Strahlentherapie
      • Goettingen, Germany, D-37075
        • Universitaetsklinikum Goettingen
      • Greifswald, Germany, D-17487
        • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
      • Greifswald, Germany, D-17489
        • Praxis fuer Haematologie und Internistische Onkologie - Greifswald
      • Gustrow, Germany, D-18273
        • Internistisch-Haematologische Gemeinschaftspraxis - Gustrow
      • Hagen, Germany, D-58095
        • St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
      • Halle, Germany, D-06108
        • Internistische Praxis - Halle
      • Halle, Germany, D-06110
        • Internistische Gemeinschaftspraxis - Halle
      • Hamburg, Germany, D-20099
        • Asklepios Klinik St. Georg
      • Hamburg, Germany, D-20246
        • Universitaetsklinikum Hamburg-Eppendorf
      • Hamm, Germany, D-59071
        • St. Marien-Hospital Hamm - Klinik Knappenstrasse
      • Hamm, Germany, D-59063
        • Evangelische Krankenhaus Hamm
      • Hannover, Germany, D-30169
        • Schwerpunktpraxis Haematologie/Onkologie - Hannover
      • Heidelberg, Germany, D-69120
        • Universitaets-Kinderklinik Heidelberg
      • Heilbronn, Germany, D-74064
        • SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen
      • Herrsching, Germany, D-82211
        • Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
      • Hildesheim, Germany, D-31134
        • Onkologische Schwerpunktpraxis
      • Hoevelhof, Germany, D-33161
        • Onkologische Gemeinschaftspraxis - Hoevelhof
      • Holzminden, Germany, D-37603
        • Evang. Hospital
      • Homburg, Germany, D-66421
        • Universitaetsklinikum des Saarlandes
      • Idar-Oberstein, Germany, D-55743
        • Clinic for Bone Marrow Transplantation and Hematology and Oncology
      • Ingolstadt, Germany, D-85049
        • Internistische Praxis - Ingolstadt
      • Jena, Germany, D-07743
        • Internistische Gemeinschaftspraxis - Jena
      • Kaiserslautern, Germany, D-67653
        • Westpfalz-Klinikum GmbH
      • Kaiserslautern, Germany, D-67655
        • Onkologische Gemeinschaftspraxis - Kaiserslautern
      • Karlsruhe, Germany, D-76137
        • St. Vincentius-Kliniken
      • Karlsruhe, Germany, D-76133
        • Staedtisches Klinikum Karlsruhe gGmbH
      • Kassel, Germany, D-34117
        • Internistische Gemeinschaftspraxis - Kassel
      • Kempten, Germany, D-87439
        • Klinikum Kempten Oberallgaeu
      • Kiel, Germany, D-24105
        • University Hospital Schleswig-Holstein - Kiel Campus
      • Koeln, Germany, D-50677
        • Praxis Fuer Haematologie Internistische Onkologie
      • Kronach, Germany, D-96317
        • Internistische Onkologische Praxis - Kronach
      • Landshut, Germany, D-84028
        • Internistische Praxis - Landshut
      • Leer, Germany, D-26789
        • Onkologische Schwerpunktpraxis - Leer
      • Lemgo, Germany, D-32657
        • Klinikum Lippe - Lemgo
      • Ludwigsburg, Germany, D-71638
        • Internistische Praxis - Ludwigsburg
      • Magdeburg, Germany, D-39120
        • Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
      • Magdeburg, Germany, D-39104
        • Staedtisches Klinikum Magdeburg - Altstadt
      • Mannheim, Germany, D-68305
        • III Medizinische Klinik Mannheim
      • Moenchengladbach, Germany, D-41239
        • Haematologische Praxis - Moenchengladbach
      • Muenchen, Germany, D-81245
        • Hamatologie/Onkologie Praxisgemeinschaft - Muenchen
      • Muenster, Germany, D-48129
        • University of Muenster
      • Muhr am See, Germany, D-91735
        • Internistische Praxis - Muhr am See
      • Munich, Germany, D-81377
        • Klinikum der Universitaet Muenchen - Grosshadern Campus
      • Munich, Germany, D-81675
        • Klinikum Rechts der Isar - Technische Universitaet Muenchen
      • Munich, Germany, D-80335
        • Munich Oncologic Practice at Elisenhof
      • Munich, Germany, D-80804
        • Krankenhaus Muenchen Schwabing
      • Munich, Germany, D-80331
        • Klinikum der Universitaet Muenchen - Innenstadt Campus
      • Neunkirchen, Germany, D-66538
        • Onkologische Schwerpunktpraxis Dr. Schmidt
      • Norderstedt, Germany, D-22844
        • Praxis fuer Haematologie und Interne Onkologie
      • Nordhausen, Germany, D-99734
        • Südharz-Krankenhaus Nordhausen gGmbH
      • Nuernberg, Germany, D-90419
        • Klinikum Nuernberg - Klinikum Nord
      • Offenbach, Germany, D-63065
        • Internistische Gemeinschaftspraxis - Offenbach
      • Oldenburg, Germany, D-26121
        • Internistische Gemeinschaftspraxis - Oldenburg
      • Ostfildern, Germany, D-73760
        • Paracelsus Karankenhaus Ruit
      • Pasewalk, Germany, D-17309
        • Asklepios Klinik Pasewalk
      • Plauen, Germany, D-08529
        • Vogtland - Klinikum Plauen GMBH
      • Postdam, Germany, D-14467
        • Klinikum Ernst von Bergmann
      • Potsdam, Germany, D-14467
        • Internistische Gemeinschaftspraxis - Potsdam
      • Regensburg, Germany, D-93049
        • Krankenhaus Barmherzige Brueder Regensburg
      • Rosenheim, Germany, D-83022
        • Staedtische Klinikum-Kinderklinik
      • Rostock, Germany, D-18057
        • Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
      • Rostock, Germany, D-18057
        • Haematologische/Onkologische Schwerpunktpraxis - Rostock
      • Saarbrucken, Germany, D-66113
        • Caritasklinik St. Theresia
      • Saarbruecke, Germany, D-66113
        • Schwerpunktpraxis fuer Haematologie und Onkologie
      • Schwerin, Germany, D-19049
        • Klinikum Schwerin
      • Siegen, Germany, D-57072
        • St. Marien - Krankenhaus Siegen GMBH
      • Stuttgart, Germany, D-70174
        • Klinik fuer Onkologie - Katharinenhospital Stuttgart
      • Stuttgart, Germany, D-70176
        • Diakonie Klinikum Stuttgart
      • Stuttgart, Germany, D-70173
        • Haematologische Praxis
      • Stuttgart, Germany, D-70199
        • Marienhospital Stuttgart
      • Stuttgart, Germany, D-70376
        • Robert-Bosch-Krankenhaus
      • Stuttgart, Germany, D-70176
        • Internistische Gemeinschaftspraxis - Stuttgart
      • Trier, Germany, D-54290
        • Krankenanstalt Mutterhaus der Borromaerinnen
      • Trier, Germany, D-54290
        • Onkologische Gemeinschaftspraxis - Trier
      • Tuebingen, Germany, D-72076
        • Southwest German Cancer Center at Eberhard-Karls-University
      • Tuebingen, Germany, D-72070
        • Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie
      • Ulm, Germany, D-89081
        • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
      • Vechta, Germany, D-49377
        • St. Marienhospital - Vechta
      • Weilheim, Germany, D-82362
        • Haematologisch-Onkologische Schwerpunktpraxis - Weilheim
      • Wendlingen, Germany, D-73240
        • Internistische Praxis - Wendlingen
      • Worms, Germany, D-67547
        • Gemeinschaftspraxis
      • Wuerzburg, Germany, D-97070
        • Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg
      • Wuppertal 2, Germany, D-42283
        • Kliniken St. Antonius
      • Wurzburg, Germany, D-97070
        • Hamatologisch - Onkologische Praxis Wurzburg
      • Zittau, Germany, D-02763
        • Internistische Praxis - Zittau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Fludarabine plus Cyclophosphamide
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
Active Comparator: Fludarabine
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 18 Month after end of treatment of the last patient
date of randomization until progression of disease or death of any cause
18 Month after end of treatment of the last patient
Overall survival
Time Frame: 18 Month after end of treatment of the last patient
Date of randomization until date of death
18 Month after end of treatment of the last patient
Duration of remission
Time Frame: 18 Month after end of treatment of the last patient
Clinical response was defined according to the guidelines of the NCI-sponsored workshop
18 Month after end of treatment of the last patient

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of side effects
Time Frame: up to 28 days after the last dose of study medication
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
Quality of life
Time Frame: 18 Month after end of treatment of the last patient
EORTC QUOL Questionnaire
18 Month after end of treatment of the last patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German CLL Study Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 1999

Primary Completion (Actual)

July 1, 2003

Study Completion (Actual)

July 1, 2007

Study Registration Dates

First Submitted

January 12, 2006

First Submitted That Met QC Criteria

January 12, 2006

First Posted (Estimate)

January 13, 2006

Study Record Updates

Last Update Posted (Actual)

May 23, 2019

Last Update Submitted That Met QC Criteria

May 21, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL4
  • EU-20538
  • GCLLSG-153
  • ISRCTN75653261
  • MEDAC-GCLLSG-CLL4
  • CDR0000455094 (Other Identifier: Clinical Data Repository)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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