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

Leukemia Clinical Trial

Official title:

Randomized Multicenter Treatment Optimization Study In Chronic Myeloid Leukemia (CML) Interferon-a Vs. Allogeneic Stem Cell Transplantation Vs. High-Dose Chemotherapy Followed By Autografting And Interferon-a Maintainance In Early Chronic Phase

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00025402
• Other study ID #: CDR0000068957
• Secondary ID: III-MK-CML-3AEU-
• Status: Active, not recruiting
• Phase: Phase 3
• First received: October 11, 2001
• Last updated: December 17, 2013
• Start date: July 1997

Study information

• Verified date: July 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Biological:
• filgrastim

• recombinant interferon alfa

Drug:
• busulfan

• cyclophosphamide

• cytarabine

• etoposide

• hydroxyurea

• idarubicin

Procedure:
• allogeneic bone marrow transplantation

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Czech Republic	Masaryk University Hospital	Brno
Germany	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	Charite - Campus Charite Mitte	Berlin
Germany	Charite - Campus Virchow Klinikum	Berlin
Germany	Haematologisch-Onkologische Schwerpunktpraxis	Berlin
Germany	Helios Klinikum Berlin	Berlin
Germany	Kinderklinik der Freier Universitaet Berlin	Berlin
Germany	Krankenhaus Neukoelln	Berlin
Germany	Onkolog - Haematolog Schwerpunktpraxis	Berlin
Germany	St. Hedwig Kranken Haus	Berlin
Germany	Tumorzentrum Berlin-Moabit	Berlin
Germany	Wenckebach - Krankenhaus	Berlin
Germany	Onkologische Schwerpunktpraxis Bielefeld	Bielefeld
Germany	Franziskus Hospital	Bietigheim
Germany	Krankenhaus Bietigheim	Bietigheim
Germany	Europahochhaus	Bochum
Germany	Kreiskrankenhaus Boeblingen	Boeblingen
Germany	Medizinische Poliklinik	Bonn
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Marienhospital Bottrop gGmbH	Bottrop
Germany	Staedtisches Klinikum Braunschweig	Braunschweig
Germany	Klinikum Bremen-Mitte	Bremen
Germany	St. Joseph Hospital	Bremerhaven
Germany	Zentralkrankenhaus	Bremerhaven
Germany	Medizinische Klinik Am Lukas - Krankenhaus	Buende
Germany	Klinikum Coburg	Coburg
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Praxis Fuer Haematologie Internistische Onkologie	Cologne
Germany	Praxis Gemeinschaft	Cologne
Germany	Onkologische Schwerpunktpraxis	Cottbus
Germany	Medizinische Klinik I	Dresden
Germany	Stadt. KH Dresden - Neustadt	Dresden
Germany	Krankenhaus Dueren	Dueren
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Michael Schaefers und Partner	Duisburg
Germany	St. Johannes Hospital - Medical Klinik II	Duisburg
Germany	Hans - Susemihl - Krankenhaus	Emden
Germany	Internistiche Praxis	Erfurt
Germany	Klinikum Erfurt	Erfurt
Germany	Praxis DR. J. Weniger	Erfurt
Germany	Medizinische Klinik III - Universitaetsklinikum Erlangen	Erlangen
Germany	Onkologische Schwerpunkt Praxis	Erlangen
Germany	St. Antonius Hospital	Eschweiler
Germany	Evangelisches Krankenhaus Essen Werden	Essen
Germany	Universitaetsklinikum Essen	Essen
Germany	Malteser Krankenhaus	Flensburg
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Onkolog Gemeinschaftspraxis	Frankfurt
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	II Medizinische Klinik - Klinikum Fuerth	Fuerth
Germany	Kreiskrankenhaus Fuessen	Fuessen
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	Klinik fuer Radioonkologie und Strahlentherapie	Goeppingen
Germany	Universitaetsklinikum Goettingen	Goettingen
Germany	DR Herbert - Nieper Krankenhaus Goslar	Goslar
Germany	Allgemeines Krankenhaus Hagen	Hagen
Germany	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH	Hagen
Germany	Allgemeines Krankenhaus Altona	Hamburg
Germany	Asklepios Klinik Barmbek	Hamburg
Germany	Haematologisch-Onkologische Praxis Altona	Hamburg
Germany	Hermann - Holthusen Institute for Radiotherapy	Hamburg
Germany	Onkologischer Schwerpunkt Lerchenfeld	Hamburg
Germany	Universitaetsklinikum Hamburg-Eppendorf	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	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
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	Gemeinschaftspraxis Brunoehler	Karlsruhe
Germany	St. Vincentius-Kliniken	Karlsruhe
Germany	Staedtisches Klinikum Karlsruhe gGmbH	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	Luebeck
Germany	Onkologische Schwerpunktpraxis Lueneburg	Lueneburg
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	Moenchengladbach
Germany	Universitaets - Kinderpoliklinik	Muenchen
Germany	Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster	Muenster
Germany	Gemeinschaftspraxis	Munich
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Krankenhaus Muenchen Neuperlach	Munich
Germany	Krankenhaus Muenchen Schwabing	Munich
Germany	Medizinische Kl. Klinikum Innenstadt Universitaet Muenchen	Munich
Germany	Praxis fuer Innere Medizin und Haematologie	Munich
Germany	Staedtisches Krankenhaus Muenchen - Harlaching	Munich
Germany	Ruppiner Klinikum GMBH	Neuruppin
Germany	Gemeinschaftspraxis	Niddatel-IIbenstadt
Germany	Praxis fuer Haematologie und Interne Onkologie	Norderstedt
Germany	Gemeinschaftspraxis	Nuernberg
Germany	Klinikum Nuernberg - Klinikum Nord	Nuernberg
Germany	Klinikum Nuernberg - Klinikum Sued	Nuernberg
Germany	Hematologische Praxis	Oldenburg
Germany	Klinikum Oldenburg	Oldenburg
Germany	Paracelsus - Klinik Osnabrueck	Osnabrueck
Germany	Staedtisches Krankenhaus	Pforzheim
Germany	Kreiskrankenhaus Radebeul	Radebeul
Germany	St. Elisabeth Krankenhaus	Ravensburg
Germany	Prosper-Hospital Recklinghausen	Recklinghausen
Germany	Hematologische Onkologische Praxis	Regensburg
Germany	Klinikum der Universitaet Regensburg	Regensburg
Germany	Krankenhaus Barmherzige Brueder Regensburg	Regensburg
Germany	Klinikum Remscheid GmbH	Remscheid
Germany	Jakobi Krankenhaus	Rheine
Germany	Caritasklinik St. Theresia	Saarbrucken
Germany	Schwerpunktpraxis fuer Haematologie und Onkologie	Saarbruecken
Germany	Saechsische Schweiz Klinik	Sebnitz
Germany	Staedt Krankenhaus	Sebnitz
Germany	Kreiskrankenhaus Siegen	Siegen
Germany	St. Marien - Krankenhaus Siegen GMBH	Siegen
Germany	Klinikum Der Hansestadt Stralsund - Klin. West	Stralsund
Germany	Diakonie Klinikum Stuttgart	Stuttgart
Germany	Haematologische Praxis	Stuttgart
Germany	Klinik fuer Onkologie - Katharinenhospital Stuttgart	Stuttgart
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	Krankenanstalt Mutterhaus der Borromaerinnen	Trier
Germany	Praxis Fuer Internistische Haematologie / Onkologie	Troisdorf
Germany	Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie	Tuebingen
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
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	Helios Kliniken Wuppertal University Hospital	Wuppertal
Germany	Praxis Fuer Haemotologie Und Internistischer Onkologie	Wuppertal
Germany	Kliniken St. Antonius	Wuppertal 2
Poland	Medical University of Gdansk	Gdansk
Poland	Silesian Medical Academy	Katowice
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Facharzt FMH Fuer Innere Medizin and Oncology	Baar
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	Grosshochstetten
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital, Luzerne	Luzerne
Switzerland	Institut Central des Hopitaux Valaisans	Sion
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Klinik Hirslanden	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
III. Medizinische Klinik Mannheim

Countries where clinical trial is conducted

Czech Republic,  Germany,  Poland,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival			No
Primary	Frequency, time-point, and duration of hematologic and cytogenetic remissions and of Philadelphia chromosome-negative and/or BCL-ABL-positive cells			No
Primary	Correlation of quality of hematological and cytogenetic remission with survival time			No
Primary	Course of the terminal phase			No
Primary	Toxicity			Yes
Primary	Effect of prognostic criteria and normal or subnormal WBC on chronic phase duration and survival time			No
Primary	Effect of early vs late high-dose therapy and autografting on feasibility, toxicity and survival times			Yes