Fludarabine With or Without Cyclophosphamide in Treating Patients With Advanced Chronic Lymphocytic Leukemia
Sponsor
German CLL Study Group (Other)
Overall Status
Completed
CT.gov ID
NCT00276848
Collaborator
(none)
375
135
2
96
2.8
0
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 Design
Study Type:
Interventional
Actual Enrollment
:
375 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date
:
Jul 1, 1999
Actual Primary Completion Date
:
Jul 1, 2003
Actual Study Completion Date
:
Jul 1, 2007
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Progression-free survival [18 Month after end of treatment of the last patient]
date of randomization until progression of disease or death of any cause
- Overall survival [18 Month after end of treatment of the last patient]
Date of randomization until date of death
- Duration of remission [18 Month after end of treatment of the last patient]
Clinical response was defined according to the guidelines of the NCI-sponsored workshop
Secondary Outcome Measures
- Incidence of side effects [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)
- Quality of life [18 Month after end of treatment of the last patient]
EORTC QUOL Questionnaire
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Allgemeines Krankenhaus - Universitatskliniken | Vienna | Austria | A-1090 | |
| 2 | Hanuschkrankenhaus | Vienna | Austria | A-1140 | |
| 3 | Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie | Ansbach | Germany | D-91522 | |
| 4 | Internistische Praxis - Arnstadt | Arnstadt | Germany | D-99310 | |
| 5 | Specialist Practice for Oncology | Aschaffenburg | Germany | D-63739 | |
| 6 | Klinikum Augsburg | Augsburg | Germany | D-86156 | |
| 7 | Kreiskrankenhaus Aurich | Aurich | Germany | D-26603 | |
| 8 | Kreiskrankenhaus | Bad Hersfeld | Germany | D-36251 | |
| 9 | Caritas-Krankenhaus Bad Mergentheim | Bad Mergentheim | Germany | D-97980 | |
| 10 | Humaine - Clinic | Bad Saarow | Germany | D-15526 | |
| 11 | Internistische Praxis - Bad Salzuflen | Bad Salzuflen | Germany | D-32105 | |
| 12 | Internistische Praxis - Bayreuth | Bayreuth | Germany | D-95448 | |
| 13 | Internistische Gemeinschaftspraxis - Bergisch Gladbach | Bergisch Gladbach | Germany | D-51429 | |
| 14 | Charite - Campus Charite Mitte | Berlin | Germany | D-10117 | |
| 15 | Onkolog - Haematolog Schwerpunktpraxis | Berlin | Germany | D-10559 | |
| 16 | Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin | Berlin | Germany | D-12200 | |
| 17 | Onkologische Gemeinschaftspraxis - Berlin | Berlin | Germany | D-13055 | |
| 18 | Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch | Berlin | Germany | D-13122 | |
| 19 | Internistische Gemeinschaftspraxis - Berlin | Berlin | Germany | D-13347 | |
| 20 | Charite - Campus Virchow Klinikum | Berlin | Germany | D-13353 | |
| 21 | Evang. Waldkrankenhaus Spandau | Berlin | Germany | D-13589 | |
| 22 | Internistische Praxis - Berlin | Berlin | Germany | D-14052 | |
| 23 | Internistische Gemeinschaftspraxis - Berlin | Berlin | Germany | D-14195 | |
| 24 | Krankenhaus Bietigheim | Bietigheim | Germany | D-74321 | |
| 25 | DIAKO Ev. Diakonie Krankenhaus gGmbH | Bremen | Germany | D-28239 | |
| 26 | Internistische Praxis - Chemnitz | Chemnitz | Germany | D-09119 | |
| 27 | Medizinische Universitaetsklinik I at the University of Cologne | Cologne | Germany | D-50924 | |
| 28 | Onkologische Schwerpunktpraxis | Cottbus | Germany | D-03046 | |
| 29 | Onkologische Gemeinschaftspraxis - Dresden | Dresden | Germany | D-01127 | |
| 30 | Krankenhaus Benrath | Dusseldorf | Germany | D-40593 | |
| 31 | St. Georg Klinikum Eisenach GmbH | Eisenach | Germany | D-99817 | |
| 32 | Hans - Susemihl - Krankenhaus | Emden | Germany | D-26721 | |
| 33 | Internistische/Onkologische Praxis - Erfurt | Erfurt | Germany | D-99084 | |
| 34 | Praxis DR. J. Weniger | Erfurt | Germany | D-99085 | |
| 35 | Klinikum Erfurt | Erfurt | Germany | D-99089 | |
| 36 | Praxis fuer Haematologie/Onkologie - Erfurt | Erfurt | Germany | D-99094 | |
| 37 | Onkologische Schwerpunkt Praxis | Erlangen | Germany | D-91052 | |
| 38 | St. Antonius Hospital | Eschweiler | Germany | D-52249 | |
| 39 | Universitaetsklinikum Essen | Essen | Germany | D-45122 | |
| 40 | Onkologische Praxis - Essen | Essen | Germany | D-45136 | |
| 41 | Evangelisches Krankenhaus Essen Werden | Essen | Germany | D-45239 | |
| 42 | Staedtische Kliniken Esslingen | Esslingen | Germany | D-73730 | |
| 43 | Internistische Gemeinschaftspraxis - Forchheim | Forchheim | Germany | D-91301 | |
| 44 | Klinikum Frankfurt (Oder) GmbH | Frankfurt | Germany | D-15236 | |
| 45 | Gemeinschaftspraxis - Freiburg | Freiburg | Germany | D-79098 | |
| 46 | Klinikum Garmisch - Partenkirchen GmbH | Garmisch-Partenkirchen | Germany | D-82467 | |
| 47 | Internistische Praxis - Gerlingen | Gerlingen | Germany | D-70839 | |
| 48 | Internistische Praxisgemeinschaft | Germering | Germany | D-82110 | |
| 49 | Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie | Giessen | Germany | D-35392 | |
| 50 | Klinik fuer Radioonkologie und Strahlentherapie | Goeppingen | Germany | D-73035 | |
| 51 | Universitaetsklinikum Goettingen | Goettingen | Germany | D-37075 | |
| 52 | Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet | Greifswald | Germany | D-17487 | |
| 53 | Praxis fuer Haematologie und Internistische Onkologie - Greifswald | Greifswald | Germany | D-17489 | |
| 54 | Internistisch-Haematologische Gemeinschaftspraxis - Gustrow | Gustrow | Germany | D-18273 | |
| 55 | St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH | Hagen | Germany | D-58095 | |
| 56 | Internistische Praxis - Halle | Halle | Germany | D-06108 | |
| 57 | Internistische Gemeinschaftspraxis - Halle | Halle | Germany | D-06110 | |
| 58 | Asklepios Klinik St. Georg | Hamburg | Germany | D-20099 | |
| 59 | Universitaetsklinikum Hamburg-Eppendorf | Hamburg | Germany | D-20246 | |
| 60 | Evangelische Krankenhaus Hamm | Hamm | Germany | D-59063 | |
| 61 | St. Marien-Hospital Hamm - Klinik Knappenstrasse | Hamm | Germany | D-59071 | |
| 62 | Schwerpunktpraxis Haematologie/Onkologie - Hannover | Hannover | Germany | D-30169 | |
| 63 | Universitaets-Kinderklinik Heidelberg | Heidelberg | Germany | D-69120 | |
| 64 | SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen | Heilbronn | Germany | D-74064 | |
| 65 | Privatklinik Dr. R. Schindlbeck GmbH & Co. KG | Herrsching | Germany | D-82211 | |
| 66 | Onkologische Schwerpunktpraxis | Hildesheim | Germany | D-31134 | |
| 67 | Onkologische Gemeinschaftspraxis - Hoevelhof | Hoevelhof | Germany | D-33161 | |
| 68 | Evang. Hospital | Holzminden | Germany | D-37603 | |
| 69 | Universitaetsklinikum des Saarlandes | Homburg | Germany | D-66421 | |
| 70 | Clinic for Bone Marrow Transplantation and Hematology and Oncology | Idar-Oberstein | Germany | D-55743 | |
| 71 | Internistische Praxis - Ingolstadt | Ingolstadt | Germany | D-85049 | |
| 72 | Internistische Gemeinschaftspraxis - Jena | Jena | Germany | D-07743 | |
| 73 | Westpfalz-Klinikum GmbH | Kaiserslautern | Germany | D-67653 | |
| 74 | Onkologische Gemeinschaftspraxis - Kaiserslautern | Kaiserslautern | Germany | D-67655 | |
| 75 | Staedtisches Klinikum Karlsruhe gGmbH | Karlsruhe | Germany | D-76133 | |
| 76 | St. Vincentius-Kliniken | Karlsruhe | Germany | D-76137 | |
| 77 | Internistische Gemeinschaftspraxis - Kassel | Kassel | Germany | D-34117 | |
| 78 | Klinikum Kempten Oberallgaeu | Kempten | Germany | D-87439 | |
| 79 | University Hospital Schleswig-Holstein - Kiel Campus | Kiel | Germany | D-24105 | |
| 80 | Praxis Fuer Haematologie Internistische Onkologie | Koeln | Germany | D-50677 | |
| 81 | Internistische Onkologische Praxis - Kronach | Kronach | Germany | D-96317 | |
| 82 | Internistische Praxis - Landshut | Landshut | Germany | D-84028 | |
| 83 | Onkologische Schwerpunktpraxis - Leer | Leer | Germany | D-26789 | |
| 84 | Klinikum Lippe - Lemgo | Lemgo | Germany | D-32657 | |
| 85 | Internistische Praxis - Ludwigsburg | Ludwigsburg | Germany | D-71638 | |
| 86 | Staedtisches Klinikum Magdeburg - Altstadt | Magdeburg | Germany | D-39104 | |
| 87 | Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg | Magdeburg | Germany | D-39120 | |
| 88 | III Medizinische Klinik Mannheim | Mannheim | Germany | D-68305 | |
| 89 | Haematologische Praxis - Moenchengladbach | Moenchengladbach | Germany | D-41239 | |
| 90 | Hamatologie/Onkologie Praxisgemeinschaft - Muenchen | Muenchen | Germany | D-81245 | |
| 91 | University of Muenster | Muenster | Germany | D-48129 | |
| 92 | Internistische Praxis - Muhr am See | Muhr am See | Germany | D-91735 | |
| 93 | Klinikum der Universitaet Muenchen - Innenstadt Campus | Munich | Germany | D-80331 | |
| 94 | Munich Oncologic Practice at Elisenhof | Munich | Germany | D-80335 | |
| 95 | Krankenhaus Muenchen Schwabing | Munich | Germany | D-80804 | |
| 96 | Klinikum der Universitaet Muenchen - Grosshadern Campus | Munich | Germany | D-81377 | |
| 97 | Klinikum Rechts Der Isar - Technische Universitaet Muenchen | Munich | Germany | D-81675 | |
| 98 | Onkologische Schwerpunktpraxis Dr. Schmidt | Neunkirchen | Germany | D-66538 | |
| 99 | Praxis fuer Haematologie und Interne Onkologie | Norderstedt | Germany | D-22844 | |
| 100 | Sudharz-Krankenhaus Nordhausen gGmbH | Nordhausen | Germany | D-99734 | |
| 101 | Klinikum Nuernberg - Klinikum Nord | Nuernberg | Germany | D-90419 | |
| 102 | Internistische Gemeinschaftspraxis - Offenbach | Offenbach | Germany | D-63065 | |
| 103 | Internistische Gemeinschaftspraxis - Oldenburg | Oldenburg | Germany | D-26121 | |
| 104 | Paracelsus Karankenhaus Ruit | Ostfildern | Germany | D-73760 | |
| 105 | Asklepios Klinik Pasewalk | Pasewalk | Germany | D-17309 | |
| 106 | Vogtland - Klinikum Plauen GMBH | Plauen | Germany | D-08529 | |
| 107 | Klinikum Ernst Von Bergmann | Postdam | Germany | D-14467 | |
| 108 | Internistische Gemeinschaftspraxis - Potsdam | Potsdam | Germany | D-14467 | |
| 109 | Krankenhaus Barmherzige Brueder Regensburg | Regensburg | Germany | D-93049 | |
| 110 | Staedtische Klinikum-Kinderklinik | Rosenheim | Germany | D-83022 | |
| 111 | Haematologische/Onkologische Schwerpunktpraxis - Rostock | Rostock | Germany | D-18057 | |
| 112 | Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock | Rostock | Germany | D-18057 | |
| 113 | Caritasklinik St. Theresia | Saarbrucken | Germany | D-66113 | |
| 114 | Schwerpunktpraxis fuer Haematologie und Onkologie | Saarbruecke | Germany | D-66113 | |
| 115 | Klinikum Schwerin | Schwerin | Germany | D-19049 | |
| 116 | St. Marien - Krankenhaus Siegen GMBH | Siegen | Germany | D-57072 | |
| 117 | Haematologische Praxis | Stuttgart | Germany | D-70173 | |
| 118 | Klinik fuer Onkologie - Katharinenhospital Stuttgart | Stuttgart | Germany | D-70174 | |
| 119 | Diakonie Klinikum Stuttgart | Stuttgart | Germany | D-70176 | |
| 120 | Internistische Gemeinschaftspraxis - Stuttgart | Stuttgart | Germany | D-70176 | |
| 121 | Marienhospital Stuttgart | Stuttgart | Germany | D-70199 | |
| 122 | Robert-Bosch-Krankenhaus | Stuttgart | Germany | D-70376 | |
| 123 | Krankenanstalt Mutterhaus der Borromaerinnen | Trier | Germany | D-54290 | |
| 124 | Onkologische Gemeinschaftspraxis - Trier | Trier | Germany | D-54290 | |
| 125 | Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie | Tuebingen | Germany | D-72070 | |
| 126 | Southwest German Cancer Center at Eberhard-Karls-University | Tuebingen | Germany | D-72076 | |
| 127 | Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm | Ulm | Germany | D-89081 | |
| 128 | St. Marienhospital - Vechta | Vechta | Germany | D-49377 | |
| 129 | Haematologisch-Onkologische Schwerpunktpraxis - Weilheim | Weilheim | Germany | D-82362 | |
| 130 | Internistische Praxis - Wendlingen | Wendlingen | Germany | D-73240 | |
| 131 | Gemeinschaftspraxis | Worms | Germany | D-67547 | |
| 132 | Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg | Wuerzburg | Germany | D-97070 | |
| 133 | Kliniken St. Antonius | Wuppertal 2 | Germany | D-42283 | |
| 134 | Hamatologisch - Onkologische Praxis Wurzburg | Wurzburg | Germany | D-97070 | |
| 135 | Internistische Praxis - Zittau | Zittau | Germany | D-02763 |
Sponsors and Collaborators
- German CLL Study Group
Investigators
- Study Chair: Michael Hallek, MD, Medizinische Universitaetsklinik I at the University of Cologne
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 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.
- 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.
- Goede V, Cramer P, Busch R, Bergmann M, Stauch M, Hopfinger G, Stilgenbauer S, Döhner 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.
- Jebaraj BMC, Tausch E, Landau DA, Bahlo J, Robrecht S, Taylor-Weiner AN, Bloehdorn J, Scheffold A, Mertens D, Böttcher S, Kneba M, Jäger U, Zenz T, Wenger MK, Fingerle-Rowson G, Wendtner C, Fink AM, Wu CJ, Eichhorst B, Fischer K, Hallek M, Döhner 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.
- 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.
Responsible Party:
German CLL Study Group
ClinicalTrials.gov Identifier:
NCT00276848
Other Study ID Numbers:
- CLL4
- EU-20538
- GCLLSG-153
- ISRCTN75653261
- MEDAC-GCLLSG-CLL4
- CDR0000455094
First Posted:
Jan 13, 2006
Last Update Posted:
May 23, 2019
Last Verified:
May 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by German CLL Study Group
Additional relevant MeSH terms: