Chemotherapy and Biological Therapy With or Without Bone Marrow or Peripheral Stem Cell Transplant in Treating Patients With Chronic Myelogenous Leukemia

Phase 3

• Conditions: Leukemia

• Registration Number: NCT00025402
• Lead Sponsor: III. Medizinische Klinik Mannheim

Brief Summary

RATIONALE: Giving chemotherapy, such as hydroxyurea, cytarabine, idarubicin, and etoposide before a donor bone marrow transplant or stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Interferon alfa may interfere with the growth of cancer cells and slow the growth of cancer. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether chemotherapy is more effective with or without interferon alfa and/or bone marrow or stem cell transplant in treating patients with chronic myelogenous leukemia.

PURPOSE: This randomized phase III trial is studying chemotherapy and biological therapy to see how well it works compared with chemotherapy, biological therapy, and donor bone marrow transplant or autologous stem cell transplant in treating patients with chronic phase chronic myelogenous leukemia.

Detailed Description

OBJECTIVES:

* Compare survival in patients with chronic myelogenous leukemia in early chronic phase treated with allogeneic bone marrow transplantation vs drug treatment with or without autologous peripheral blood stem cell transplantation.

* Compare survival of patients with late-phase disease treated with high-dose cytarabine vs low-dose cytarabine followed by autografting and interferon alfa maintenance.

* Compare survival of patients not responding cytogenetically to treatment with continued interferon alfa vs hydroxyurea.

* Determine frequency, time-point, and duration of hematological and cytogenetic remissions and of Philadelphia chromosome-negative and/or BCR-ABL-positive cells on the various treatments.

* Correlate the quality of hematological and cytogenetic remissions with survival time in patients treated with these regimens.

* Compare the course of the terminal phase in patients treated with these regimens.

* Compare the toxic effects of these regimens in these patients.

* Determine the effect of prognostic criteria and normal or subnormal WBC on chronic phase duration and survival time in patients treated with these regimens.

* Compare the effect of early vs late high-dose therapy plus autografting on feasibility, toxicity, and survival times in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to eligibility for transplantation (yes vs no).

All patients undergo cytoreduction comprising hydroxyurea (HU) IV daily.

Patients who are ineligible for or refuse transplantation are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive interferon alfa (IFN) subcutaneously (SC) daily. After 2 weeks of IFN therapy, patients also receive low-dose cytarabine (ARA-C) SC once daily for 10-15 days each month. Patients who do not achieve cytogenetic remission within 12 months continue to receive HU.

* Arm II: Patients receive IFN SC daily. After 2 weeks of IFN therapy, patients also receive low-dose ARA-C SC daily for 10-15 days each month. Patients who do not achieve cytogenetic remission within 12 months continue to receive IFN therapy SC daily.

Patients who are eligible for transplantation with a related donor undergo allogeneic bone marrow transplantation. Patients may receive HU or IFN prior to transplantation. Patients may also receive oral high-dose busulfan daily for 4 days with or without cyclophosphamide or cyclophosphamide with total body irradiation.

Patients who are eligible for transplantation but do not have a related donor undergo peripheral blood stem cell (PBSC) harvest and are randomized to 1 of 2 treatment arms.

* Arm III: Patients receive IFN and low-dose ARA-C as in arm I. Patients who accelerate on treatment may undergo autologous PBSC transplantation.

* Arm IV: Patients receive idarubicin IV, ARA-C IV over 2 hours, and etoposide IV on days 1-3. Patients then undergo leukapheresis. Beginning on day 8, patients receive filgrastim (G-CSF) SC daily until end of leukapheresis. Patients then receive oral high-dose busulfan daily for 4 consecutive days. The following day, patients undergo reinfusion of autologous PBSC. After blood count recovery, patients receive maintenance IFN 3 times weekly for 8 weeks and then daily.

Patients are followed every 3 months for 3 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study within 5 years.

Study Timeline

• Study Start: 1997-07
• Study First Submitted: 2001-10-11
• Status Verified: 2002-07
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Last Update Submitted: 2013-12-17
• Last Update Posted: 2013-12-18

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Toxicity
Survival
Correlation of quality of hematological and cytogenetic remission with survival time
Course of the terminal phase
Frequency, time-point, and duration of hematologic and cytogenetic remissions and of Philadelphia chromosome-negative and/or BCL-ABL-positive cells
Effect of prognostic criteria and normal or subnormal WBC on chronic phase duration and survival time
Effect of early vs late high-dose therapy and autografting on feasibility, toxicity and survival times

Trial Locations

Locations (178)

Tumorzentrum Berlin-Moabit; 🇩🇪 Berlin, Germany

Wenckebach - Krankenhaus; 🇩🇪 Berlin, Germany

Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie; 🇩🇪 Ansbach, Germany

Haematologisch Onkologische Praxis; 🇩🇪 Aachen, Germany

II. Medizinische Klinik; 🇩🇪 Aschaffenburg, Germany

Haematologische Praxis; 🇩🇪 Stuttgart, Germany

Krankenhaus Neukoelln; 🇩🇪 Berlin, Germany

Klinikum Augsburg; 🇩🇪 Augsburg, Germany

Kinderklinik der Freier Universitaet Berlin; 🇩🇪 Berlin, Germany

Kinderklinik - Universitaetsklinikum Aachen; 🇩🇪 Aachen, Germany

Urologische Klinik - Universitaetsklinikum Aachen; 🇩🇪 Aachen, Germany

Klinikum Bremen-Mitte; 🇩🇪 Bremen, Germany

Marienhospital Bottrop gGmbH; 🇩🇪 Bottrop, Germany

Internistiche Praxis; 🇩🇪 Erfurt, Germany

Onkolog Gemeinschaftspraxis; 🇩🇪 Frankfurt, Germany

St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH; 🇩🇪 Hagen, Germany

Klinik fuer Radioonkologie und Strahlentherapie; 🇩🇪 Goeppingen, Germany

Universitaetsklinikum Freiburg; 🇩🇪 Freiburg, Germany

Klinikum Herford; 🇩🇪 Herford, Germany

Kreiskrankenhaus Mellrichstadt; 🇩🇪 Mellrichstad, Germany

Klinikum Kempten Oberallgaeu; 🇩🇪 Kempten, Germany

Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster; 🇩🇪 Muenster, Germany

St. Marien-Hospital Hamm - Klinik Knappenstrasse; 🇩🇪 Hamm, Germany

Medizinische Universitaetsklinik und Poliklinik; 🇩🇪 Heidelberg, Germany

Caritas - Krakenhaus Lebach; 🇩🇪 Lebach, Germany

Medizinische Kl. Klinikum Innenstadt Universitaet Muenchen; 🇩🇪 Munich, Germany

Gemeinschaftspraxis Brunoehler; 🇩🇪 Karlsruhe, Germany

Haematologische / Onkologische Schwerpunktpraxis; 🇩🇪 Krefeld, Germany

Philipps-Universitaet Marburg Klinikum; 🇩🇪 Marburg, Germany

Klinikum Krefeld GmbH; 🇩🇪 Krefeld, Germany

Krankenhaus Maria Hilf GmbH; 🇩🇪 Moenchengladbach, Germany

Universitaets - Kinderpoliklinik; 🇩🇪 Muenchen, Germany

Praxis Fuer Haematologie/Onkologie; 🇩🇪 Luebeck, Germany

Schwerpunktpraxis fuer Haematologie und Onkologie; 🇩🇪 Saarbruecken, Germany

Kreiskrankenhaus Radebeul; 🇩🇪 Radebeul, Germany

Krankenhaus Muenchen Neuperlach; 🇩🇪 Munich, Germany

St. Elisabeth Krankenhaus; 🇩🇪 Ravensburg, Germany

Prosper-Hospital Recklinghausen; 🇩🇪 Recklinghausen, Germany

Klinikum Remscheid GmbH; 🇩🇪 Remscheid, Germany

Robert-Bosch-Krankenhaus; 🇩🇪 Stuttgart, Germany

Kliniken St. Antonius; 🇩🇪 Wuppertal 2, Germany

Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie; 🇩🇪 Tuebingen, Germany

Kreiskrankenhaus Siegen; 🇩🇪 Siegen, Germany

FMH f. Innere Medizin and Hematologie; 🇨🇭 Grosshochstetten, Switzerland

Klinik Hirslanden; 🇨🇭 Zurich, Switzerland

Universitaetsklinikum Ulm; 🇩🇪 Ulm, Germany

Hospital Universitario Virgen de la Victoria; 🇪🇸 Malaga, Spain

Praxis Fuer Internistische Haematologie / Onkologie; 🇩🇪 Troisdorf, Germany

Bezirksspital Dornach; 🇨🇭 Dornach, Switzerland

Kantonsspital - St. Gallen; 🇨🇭 St. Gallen, Switzerland

Klinik fuer Onkologie - Katharinenhospital Stuttgart; 🇩🇪 Stuttgart, Germany

Helios Kliniken Wuppertal University Hospital; 🇩🇪 Wuppertal, Germany

Kantonsspital, Luzerne; 🇨🇭 Luzerne, Switzerland

Masaryk University Hospital; 🇨🇿 Brno, Czech Republic

Universitaetsspital-Basel; 🇨🇭 Basel, Switzerland

St. Irmgardis Krankenhaus; 🇩🇪 Viersen-Suechteln, Germany

Kreiskrankenhaus; 🇩🇪 Waldroel, Germany

Krankenhaus Hohe Warte Mediziniche Klinik; 🇩🇪 Bayreuth, Germany

Klinikum St. Marien; 🇩🇪 Amberg, Germany

St. Hedwig Kranken Haus; 🇩🇪 Berlin, Germany

Onkologische Schwerpunktpraxis Bielefeld; 🇩🇪 Bielefeld, Germany

Helios Klinikum Berlin; 🇩🇪 Berlin, Germany

Franziskus Hospital; 🇩🇪 Bietigheim, Germany

Krankenhaus Bietigheim; 🇩🇪 Bietigheim, Germany

Europahochhaus; 🇩🇪 Bochum, Germany

Universitaetsklinikum Bonn; 🇩🇪 Bonn, Germany

Staedtisches Klinikum Braunschweig; 🇩🇪 Braunschweig, Germany

Kreiskrankenhaus Boeblingen; 🇩🇪 Boeblingen, Germany

Medizinische Poliklinik; 🇩🇪 Bonn, Germany

Klinikum Coburg; 🇩🇪 Coburg, Germany

Medizinische Klinik Am Lukas - Krankenhaus; 🇩🇪 Buende, Germany

Praxis Gemeinschaft; 🇩🇪 Cologne, Germany

Praxis Fuer Haematologie Internistische Onkologie; 🇩🇪 Cologne, Germany

Medizinische Universitaetsklinik I at the University of Cologne; 🇩🇪 Cologne, Germany

Onkologische Schwerpunktpraxis; 🇩🇪 Cottbus, Germany

Stadt. KH Dresden - Neustadt; 🇩🇪 Dresden, Germany

Krankenhaus Dueren; 🇩🇪 Dueren, Germany

Universitaetsklinikum Duesseldorf; 🇩🇪 Duesseldorf, Germany

Medizinische Klinik I; 🇩🇪 Dresden, Germany

Michael Schaefers und Partner; 🇩🇪 Duisburg, Germany

Hans - Susemihl - Krankenhaus; 🇩🇪 Emden, Germany

Klinikum Erfurt; 🇩🇪 Erfurt, Germany

Praxis DR. J. Weniger; 🇩🇪 Erfurt, Germany

Onkologische Schwerpunkt Praxis; 🇩🇪 Erlangen, Germany

Medizinische Klinik III - Universitaetsklinikum Erlangen; 🇩🇪 Erlangen, Germany

St. Antonius Hospital; 🇩🇪 Eschweiler, Germany

Klinikum der J.W. Goethe Universitaet; 🇩🇪 Frankfurt, Germany

II Medizinische Klinik - Klinikum Fuerth; 🇩🇪 Fuerth, Germany

Kreiskrankenhaus Fuessen; 🇩🇪 Fuessen, Germany

Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie; 🇩🇪 Giessen, Germany

Evangelisches Krankenhaus Essen Werden; 🇩🇪 Essen, Germany

Klinikum Garmisch - Partenkirchen GmbH; 🇩🇪 Garmisch-Partenkirchen, Germany

DR Herbert - Nieper Krankenhaus Goslar; 🇩🇪 Goslar, Germany

Allgemeines Krankenhaus Altona; 🇩🇪 Hamburg, Germany

Klinik und Poliklinik fuer Urologie und Kinderurologie; 🇩🇪 Giessen, Germany

Universitaetsklinikum Goettingen; 🇩🇪 Goettingen, Germany

Allgemeines Krankenhaus Hagen; 🇩🇪 Hagen, Germany

Hermann - Holthusen Institute for Radiotherapy; 🇩🇪 Hamburg, Germany

Evangelische Krankenhaus Hamm; 🇩🇪 Hamm, Germany

Krankenhaus Siloah - Medizinische Klinik II; 🇩🇪 Hannover, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Haematologisch-Onkologische Praxis Altona; 🇩🇪 Hamburg, Germany

Universitaetsklinikum des Saarlandes; 🇩🇪 Homburg, Germany

Clinic for Bone Marrow Transplantation and Hematology and Oncology; 🇩🇪 Idar-Oberstein, Germany

Diakonissen - Krankenhaus; 🇩🇪 Karlsruhe-Rueppur, Germany

Klinikum Kassel; 🇩🇪 Kassel, Germany

Praxis am Evangelischen Krankenhaus Bethanien; 🇩🇪 Iserlohn, Germany

Staedtisches Klinikum Karlsruhe gGmbH; 🇩🇪 Karlsruhe, Germany

St. Vincentius-Kliniken; 🇩🇪 Karlsruhe, Germany

University Hospital Schleswig-Holstein - Kiel Campus; 🇩🇪 Kiel, Germany

Vinzentiuskrankenhaus; 🇩🇪 Landau, Germany

Klinikum Lippe - Lemgo; 🇩🇪 Lemgo, Germany

Onkologische Schwerpunktpraxis - Leer; 🇩🇪 Leer, Germany

St Marienkrankenhaus; 🇩🇪 Ludwigshafen, Rhein, Germany

Onkologische Schwerpunktpraxis Lueneburg; 🇩🇪 Lueneburg, Germany

Luisenkrankenhaus; 🇩🇪 Lindenfels, Germany

Gemeinschaftspraxis; 🇩🇪 Nuernberg, Germany

Klinikum Minden; 🇩🇪 Minden, Germany

Krankenhaus Muenchen Schwabing; 🇩🇪 Munich, Germany

Praxis fuer Innere Medizin und Haematologie; 🇩🇪 Munich, Germany

Klinikum Rechts Der Isar - Technische Universitaet Muenchen; 🇩🇪 Munich, Germany

Klinikum Nuernberg - Klinikum Nord; 🇩🇪 Nuernberg, Germany

Ruppiner Klinikum GMBH; 🇩🇪 Neuruppin, Germany

Klinikum Nuernberg - Klinikum Sued; 🇩🇪 Nuernberg, Germany

Paracelsus - Klinik Osnabrueck; 🇩🇪 Osnabrueck, Germany

Hematologische Praxis; 🇩🇪 Oldenburg, Germany

Klinikum Oldenburg; 🇩🇪 Oldenburg, Germany

Saechsische Schweiz Klinik; 🇩🇪 Sebnitz, Germany

Staedt Krankenhaus; 🇩🇪 Sebnitz, Germany

Staedtisches Krankenhaus; 🇩🇪 Pforzheim, Germany

Diakonie Klinikum Stuttgart; 🇩🇪 Stuttgart, Germany

Hematologische Onkologische Praxis; 🇩🇪 Regensburg, Germany

Jakobi Krankenhaus; 🇩🇪 Rheine, Germany

Klinikum Der Hansestadt Stralsund - Klin. West; 🇩🇪 Stralsund, Germany

Klinikum Der Stadt Villingen - Schwenningen; 🇩🇪 Villingen-Schwenningen, Germany

Southwest German Cancer Center at Eberhard-Karls-University; 🇩🇪 Tuebingen, Germany

Bundeswehr Krakenhaus; 🇩🇪 Ulm, Germany

Krankenhaus St. Michael; 🇩🇪 Voeklingen, Germany

St. Willehad Hospital; 🇩🇪 Wilhelmshaven, Germany

Deutsche Klinik fuer Diagnostik; 🇩🇪 Wiesbaden, Germany

Praxis Fuer Haemotologie Und Internistischer Onkologie; 🇩🇪 Wuppertal, Germany

Haematologisch-Onkologische Schwerpunktpraxis; 🇩🇪 Berlin, Germany

Asklepios Klinik Barmbek; 🇩🇪 Hamburg, Germany

Universitaetsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Onkologischer Schwerpunkt Lerchenfeld; 🇩🇪 Hamburg, Germany

St. Johannes Hospital - Medical Klinik II; 🇩🇪 Duisburg, Germany

Haematologie Und Internistische Onkologie; 🇩🇪 Hanau, Germany

III Medizinische Klinik Mannheim; 🇩🇪 Mannheim, Germany

Staedtisches Krankenhaus Muenchen - Harlaching; 🇩🇪 Munich, Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus; 🇩🇪 Munich, Germany

Praxis fuer Haematologie und Interne Onkologie; 🇩🇪 Norderstedt, Germany

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland

Caritasklinik St. Theresia; 🇩🇪 Saarbrucken, Germany

Krankenhaus Barmherzige Brueder Regensburg; 🇩🇪 Regensburg, Germany

Klinikum der Universitaet Regensburg; 🇩🇪 Regensburg, Germany

St. Marien - Krankenhaus Siegen GMBH; 🇩🇪 Siegen, Germany

Krankenanstalt Mutterhaus der Borromaerinnen; 🇩🇪 Trier, Germany

Facharzt Fuer Onkologie-Hematologie; 🇨🇭 Bern, Switzerland

Inneremedizin FMH; 🇨🇭 Breitenbach, Switzerland

St. Joseph Hospital; 🇩🇪 Bremerhaven, Germany

Charite - Campus Virchow Klinikum; 🇩🇪 Berlin, Germany

Universitaetsklinikum Essen; 🇩🇪 Essen, Germany

Charite - Campus Charite Mitte; 🇩🇪 Berlin, Germany

Malteser Krankenhaus; 🇩🇪 Flensburg, Germany

Klinik Konstanz; 🇩🇪 Konstanz, Germany

Onkolog - Haematolog Schwerpunktpraxis; 🇩🇪 Berlin, Germany

Zentralkrankenhaus; 🇩🇪 Bremerhaven, Germany

Klinikum der Friedrich-Schiller Universitaet Jena; 🇩🇪 Jena, Germany

Klinikum der Stadt Ludwigshafen am Rhein; 🇩🇪 Ludwigshafen am Rhein, Germany

Silesian Medical Academy; 🇵🇱 Katowice, Poland

Kantonspital Aarau; 🇨🇭 Aarau, Switzerland

Facharzt FMH Fuer Innere Medizin and Oncology; 🇨🇭 Baar, Switzerland

Oncology Institute of Southern Switzerland; 🇨🇭 Bellinzona, Switzerland

Inselspital Bern; 🇨🇭 Bern, Switzerland

Medical University of Gdansk; 🇵🇱 Gdansk, Poland

Hopital Cantonal Universitaire de Geneve; 🇨🇭 Geneva, Switzerland

Institut Central des Hopitaux Valaisans; 🇨🇭 Sion, Switzerland

UniversitaetsSpital Zuerich; 🇨🇭 Zurich, Switzerland