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

NCT ID: NCT00025402

Last Updated: 2013-12-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-07-31

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.

Conditions

Leukemia

Keywords

chronic phase chronic myelogenous leukemia; chronic myelogenous leukemia, BCR-ABL1 positive; Philadelphia chromosome negative chronic myelogenous leukemia; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia, BCR-ABL1 negative

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

recombinant interferon alfa

Intervention Type: BIOLOGICAL

busulfan

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

hydroxyurea

Intervention Type: DRUG

idarubicin

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia in chronic phase

• Previously untreated
• Patients negative for Philadelphia chromosome and BCR-ABL translocation must fulfill at least 1 of the following criteria:

• Impaired health status with reduced exercise tolerance
• Spleen-related symptoms in cases of splenomegaly
• Weight loss greater than 10% in 6 months
• Fever greater than 38.5 degrees C on 5 consecutive days
• Clinically relevant bone pain
• Leukocytosis greater than 5,000/mm^3
• Thrombocytosis greater than 100,000/mm^3

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No other concurrent malignancy that is likely to require treatment during study or that is likely to reduce life expectancy
• No severe concurrent disease or other cause that would preclude study
• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior interferon

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

III. Medizinische Klinik Mannheim

OTHER

Sponsor Role: lead

Principal Investigators

Ruediger Hehlmann, MD

Role: STUDY_CHAIR

III. Medizinische Klinik Mannheim

Locations

Masaryk University Hospital

Brno, , Czechia

Haematologisch Onkologische Praxis

Aachen, , Germany

Kinderklinik - Universitaetsklinikum Aachen

Aachen, , Germany

Urologische Klinik - Universitaetsklinikum Aachen

Aachen, , Germany

Kreiskrankenhaus

Aalen, , Germany

Klinikum St. Marien

Amberg, , Germany

Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie

Ansbach, , Germany

II. Medizinische Klinik

Aschaffenburg, , Germany

Haematologische Praxis

Augsburg, , Germany

Klinikum Augsburg

Augsburg, , Germany

Kreiskrankenhaus

Bad Hersfeld, , Germany

Krankenhaus Hohe Warte Mediziniche Klinik

Bayreuth, , Germany

St. Hedwig Kranken Haus

Berlin, , Germany

Tumorzentrum Berlin-Moabit

Berlin, , Germany

Wenckebach - Krankenhaus

Berlin, , Germany

Helios Klinikum Berlin

Berlin, , Germany

Haematologisch-Onkologische Schwerpunktpraxis

Berlin, , Germany

Charite - Campus Charite Mitte

Berlin, , Germany

Onkolog - Haematolog Schwerpunktpraxis

Berlin, , Germany

Krankenhaus Neukoelln

Berlin, , Germany

Charite - Campus Virchow Klinikum

Berlin, , Germany

Kinderklinik der Freier Universitaet Berlin

Berlin, , Germany

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, , Germany

Franziskus Hospital

Bietigheim, , Germany

Krankenhaus Bietigheim

Bietigheim, , Germany

Europahochhaus

Bochum, , Germany

Universitaetsklinikum Bonn

Bonn, , Germany

Medizinische Poliklinik

Bonn, , Germany

Marienhospital Bottrop gGmbH

Bottrop, , Germany

Kreiskrankenhaus Boeblingen

Böblingen, , Germany

Staedtisches Klinikum Braunschweig

Braunschweig, , Germany

Klinikum Bremen-Mitte

Bremen, , Germany

St. Joseph Hospital

Bremerhaven, , Germany

Zentralkrankenhaus

Bremerhaven, , Germany

Medizinische Klinik Am Lukas - Krankenhaus

Bünde, , Germany

Klinikum Coburg

Coburg, , 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

Medizinische Klinik I

Dresden, , Germany

Michael Schaefers und Partner

Duisburg, , Germany

St. Johannes Hospital - Medical Klinik II

Duisburg, , Germany

Krankenhaus Dueren

Düren, , Germany

Universitaetsklinikum Duesseldorf

Düsseldorf, , Germany

Hans - Susemihl - Krankenhaus

Emden, , Germany

Internistiche Praxis

Erfurt, , 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

Universitaetsklinikum Essen

Essen, , Germany

Evangelisches Krankenhaus Essen Werden

Essen, , Germany

Malteser Krankenhaus

Flensburg, , Germany

Onkolog Gemeinschaftspraxis

Frankfurt, , Germany

Klinikum der J.W. Goethe Universitaet

Frankfurt, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

II Medizinische Klinik - Klinikum Fuerth

Fürth, , Germany

Kreiskrankenhaus Fuessen

Füssen, , Germany

Klinikum Garmisch - Partenkirchen GmbH

Garmisch-Partenkirchen, , Germany

Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie

Giessen, , Germany

Klinik und Poliklinik fuer Urologie und Kinderurologie

Giessen, , Germany

DR Herbert - Nieper Krankenhaus Goslar

Goslar, , Germany

Klinik fuer Radioonkologie und Strahlentherapie

Göppingen, , Germany

Universitaetsklinikum Goettingen

Göttingen, , Germany

Allgemeines Krankenhaus Hagen

Hagen, , Germany

St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

Hagen, , Germany

Allgemeines Krankenhaus Altona

Hamburg, , Germany

Hermann - Holthusen Institute for Radiotherapy

Hamburg, , Germany

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Onkologischer Schwerpunkt Lerchenfeld

Hamburg, , Germany

Asklepios Klinik Barmbek

Hamburg, , Germany

Haematologisch-Onkologische Praxis Altona

Hamburg, , Germany

Evangelische Krankenhaus Hamm

Hamm, , Germany

St. Marien-Hospital Hamm - Klinik Knappenstrasse

Hamm, , Germany

Haematologie Und Internistische Onkologie

Hanau, , Germany

Krankenhaus Siloah - Medizinische Klinik II

Hanover, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Medizinische Universitaetsklinik und Poliklinik

Heidelberg, , Germany

Klinikum Herford

Herford, , Germany

Universitaetsklinikum des Saarlandes

Homburg, , Germany

Clinic for Bone Marrow Transplantation and Hematology and Oncology

Idar-Oberstein, , Germany

Praxis am Evangelischen Krankenhaus Bethanien

Iserlohn, , Germany

Klinikum der Friedrich-Schiller Universitaet Jena

Jena, , Germany

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, , Germany

Gemeinschaftspraxis Brunoehler

Karlsruhe, , Germany

St. Vincentius-Kliniken

Karlsruhe, , Germany

Diakonissen - Krankenhaus

Karlsruhe-Rueppur, , Germany

Klinikum Kassel

Kassel, , Germany

Klinikum Kempten Oberallgaeu

Kempten, , Germany

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, , Germany

Klinik Konstanz

Konstanz, , Germany

Haematologische / Onkologische Schwerpunktpraxis

Krefeld, , Germany

Klinikum Krefeld GmbH

Krefeld, , Germany

Vinzentiuskrankenhaus

Landau, , Germany

Caritas - Krakenhaus Lebach

Lebach, , Germany

Onkologische Schwerpunktpraxis - Leer

Leer, , Germany

Klinikum Lippe - Lemgo

Lemgo, , Germany

Luisenkrankenhaus

Lindenfels, , Germany

Klinikum der Stadt Ludwigshafen am Rhein

Ludwigshafen am Rhein, , Germany

St Marienkrankenhaus

Ludwigshafen, Rhein, , Germany

Praxis Fuer Haematologie/Onkologie

Lübeck, , Germany

Onkologische Schwerpunktpraxis Lueneburg

Lüneburg, , Germany

Gemeinschaftspraxis

Mannheim, , Germany

III Medizinische Klinik Mannheim

Mannheim, , Germany

Philipps-Universitaet Marburg Klinikum

Marburg, , Germany

Kreiskrankenhaus Mellrichstadt

Mellrichstad, , Germany

Klinikum Minden

Minden, , Germany

Krankenhaus Maria Hilf GmbH

Mönchengladbach, , Germany

Gemeinschaftspraxis

Munich, , Germany

Munich, , Germany

Krankenhaus Muenchen Schwabing

Munich, , Germany

Medizinische Kl. Klinikum Innenstadt Universitaet Muenchen

Munich, , Germany

Praxis fuer Innere Medizin und Haematologie

Munich, , Germany

Munich, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Staedtisches Krankenhaus Muenchen - Harlaching

Munich, , Germany

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, , Germany

Krankenhaus Muenchen Neuperlach

Munich, , Germany

Universitaets - Kinderpoliklinik

München, , Germany

Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster

Münster, , Germany

Ruppiner Klinikum GMBH

Neuruppin, , Germany

Gemeinschaftspraxis

Niddatel-IIbenstadt, , Germany

Praxis fuer Haematologie und Interne Onkologie

Norderstedt, , Germany

Gemeinschaftspraxis

Nuremberg, , Germany

Klinikum Nuernberg - Klinikum Nord

Nuremberg, , Germany

Klinikum Nuernberg - Klinikum Sued

Nuremberg, , Germany

Hematologische Praxis

Oldenburg, , Germany

Klinikum Oldenburg

Oldenburg, , Germany

Paracelsus - Klinik Osnabrueck

Osnabrück, , Germany

Staedtisches Krankenhaus

Pforzheim, , Germany

Kreiskrankenhaus Radebeul

Radebeul, , Germany

St. Elisabeth Krankenhaus

Ravensburg, , Germany

Prosper-Hospital Recklinghausen

Recklinghausen, , Germany

Hematologische Onkologische Praxis

Regensburg, , Germany

Krankenhaus Barmherzige Brueder Regensburg

Regensburg, , Germany

Klinikum der Universitaet Regensburg

Regensburg, , Germany

Klinikum Remscheid GmbH

Remscheid, , Germany

Jakobi Krankenhaus

Rheine, , Germany

Caritasklinik St. Theresia

Saarbrücken, , Germany

Schwerpunktpraxis fuer Haematologie und Onkologie

Saarbrücken, , Germany

Saechsische Schweiz Klinik

Sebnitz, , Germany

Staedt Krankenhaus

Sebnitz, , Germany

St. Marien - Krankenhaus Siegen GMBH

Siegen, , Germany

Kreiskrankenhaus Siegen

Siegen, , Germany

Klinikum Der Hansestadt Stralsund - Klin. West

Stralsund, , Germany

Robert-Bosch-Krankenhaus

Stuttgart, , Germany

Haematologische Praxis

Stuttgart, , Germany

Klinik fuer Onkologie - Katharinenhospital Stuttgart

Stuttgart, , Germany

Diakonie Klinikum Stuttgart

Stuttgart, , Germany

Krankenanstalt Mutterhaus der Borromaerinnen

Trier, , Germany

Trier, , Germany

Praxis Fuer Internistische Haematologie / Onkologie

Troisdorf, , Germany

Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie

Tübingen, , Germany

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, , Germany

Bundeswehr Krakenhaus

Ulm, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

St. Irmgardis Krankenhaus

Viersen-Suechteln, , Germany

Klinikum Der Stadt Villingen - Schwenningen

Villingen-Schwenningen, , Germany

Krankenhaus St. Michael

Voeklingen, , Germany

Kreiskrankenhaus

Waldroel, , Germany

Deutsche Klinik fuer Diagnostik

Wiesbaden, , Germany

St. Willehad Hospital

Wilhelmshaven, , Germany

Praxis Fuer Haemotologie Und Internistischer Onkologie

Wuppertal, , Germany

Helios Kliniken Wuppertal University Hospital

Wuppertal, , Germany

Kliniken St. Antonius

Wuppertal, , Germany

Medical University of Gdansk

Gdansk, , Poland

Silesian Medical Academy

Katowice, , Poland

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Kantonspital Aarau

Aarau, , Switzerland

Facharzt FMH Fuer Innere Medizin and Oncology

Baar, , Switzerland

Basel, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Facharzt Fuer Onkologie-Hematologie

Bern, , Switzerland

Inselspital Bern

Bern, , Switzerland

Inneremedizin FMH

Breitenbach, , Switzerland

Bezirksspital Dornach

Dornach, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

FMH f. Innere Medizin and Hematologie

Gross Höchstetten, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital, Luzerne

Luzerne, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Institut Central des Hopitaux Valaisans

Sion, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Czechia; Germany; Poland; Spain; Switzerland

Other Identifiers

III-MK-CML-3A

Identifier Type: -

Identifier Source: secondary_id

EU-20118

Identifier Type: -

Identifier Source: secondary_id

CDR0000068957

Identifier Type: -

Identifier Source: org_study_id