Imatinib Mesylate With or Without Interferon Alfa or Cytarabine Compared With Interferon Alfa Followed by Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

May 2, 2018 updated by: Prof. Dr. Dr. h.c. R. Hehlmann, Heidelberg University

Treatment Optimization Trial in Chronic Myeloid Leukemia (CML) - Randomized Controlled Comparison of Imatinib vs. Imatinib/Interferon-alpha vs. Imatinib/Low-Dose AraC vs. Interferon-alpha Standard Therapy and Determination of the Role of Allografting in Newly Diagnosed Chronic Phase

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, imatinib mesylate may stop the growth of cancer cells by blocking the enzymes needed for cancer cell growth. 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 which treatment regimen is most effective in treating chronic phase chronic myelogenous leukemia.

PURPOSE: This randomized phase III trial is studying imatinib mesylate with or without interferon alfa or cytarabine to see how well it works compared with interferon alfa followed by donor stem cell transplant in treating patients with newly diagnosed chronic phase chronic myelogenous leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the hematologic, cytogenetic, and molecular response rates in patients with newly diagnosed chronic phase chronic myelogenous leukemia treated with imatinib mesylate alone or with interferon alfa or low-dose cytarabine vs interferon alfa standard therapy.
  • Compare the group-dependent, progression-free and overall survival and time to progression in patients treated with these regimens.
  • Compare the efficacy of allogeneic stem cell transplantation vs imatinib mesylate-based therapy in patients eligible for transplantation.
  • Compare the efficacy of reduced-intensity conditioning vs standard conditioning in patients over 45 years of age.
  • Determine the time to and duration of hematologic, cytogenetic, and molecular responses and correlate these factors in patients treated with these regimens.
  • Compare the short- and long-term adverse effects of these regimens in these patients.
  • Compare the presentation, duration, and responses to therapy of accelerated and blastic phases in patients treated with these regimens.
  • Determine the survival of high-risk patients after early allografting.
  • Determine the influence of pre-transplantation therapies on the outcome of allogeneic stem cell transplantation in these patients.

OUTLINE: This is a randomized, multicenter, pilot study. Patients are stratified according to participating center. Patients with low- to intermediate-risk disease are randomized to 1 of 4 treatment arms. Patients with high-risk disease are randomized to 1 of 3 treatment arms with imatinib mesylate-based regimens.

  • Arm I: Patients receive oral imatinib mesylate once daily for up to 12 months in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral imatinib mesylate as in arm I. Patients also receive interferon alfa subcutaneously (SC) 3 times a week beginning at least 3 months after the start of imatinib mesylate.
  • Arm III: Patients receive oral imatinib mesylate as in arm I. Patients also receive cytarabine SC up to twice daily for 5 days monthly beginning at least 3 months after the start of imatinib mesylate.
  • Arm IV: After initial cytoreduction with hydroxyurea, patients receive interferon alfa SC daily with or without hydroxyurea. In the absence of a complete response after 3 months, patients may also receive low-dose cytarabine SC once daily. Treatment continues for up to 21 months.

Patients who fail interferon alfa therapy are crossed over to receive imatinib mesylate.

Patients who fail therapy with imatinib mesylate and are eligible for an allogeneic transplantation are stratified according to availability of donor (HLA-identical related vs unrelated), status, and participating center. Patients are randomized to receive an allogeneic transplantation or continue any salvage therapy.

Patients who are not eligible for allogeneic transplantation receive hydroxyurea and cytarabine or high-dose chemotherapy with autologous stem cell rescue followed by interferon- or imatinib mesylate-based therapy.

Patients over 45 years of age are further randomized to receive an age-adjusted standard conditioning regimen or reduced intensity preparative regimen (mini transplantation) prior to allogeneic transplantation.

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

PROJECTED ACCRUAL: A total of 1,600 patients (400 per treatment arm) will be accrued for this study within 4-5 years.

Study Type

Interventional

Enrollment (Actual)

1551

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

  • Germany
      • Aachen, Germany, 52074
        • Krankenhaus / Klinikum Krefeld
      • Aurich, Germany, 26603
        • Kreiskrankenhaus Aurich
      • Bad Hersfeld, Germany, 36251
        • Kreiskrankenhaus
      • Berlin, Germany, D-10117
        • Schwerpunktpraxis fuer Haematologie und Internistische Onkologie
      • Berlin, Germany, 13357
        • Haematologisch-Onkologische Schwerpunktpraxis
      • Berlin, Germany, 10115
        • St. Hedwig Krankenhaus
      • Berlin, Germany, D-12103
        • Gemeinschaftspraxis fuer Haematologie und Internistische Onkologie
      • Bielefeld, Germany, D-33602
        • Onkologische Schwerpunktpraxis Bielefeld
      • Bonn, Germany, D-53117
        • Augustinum
      • Brandenburg, Germany, 14770
        • Hamatologische Sprechstunde
      • Bremen, Germany, D-28205
        • Praxis Dres. F.& G. Doering
      • Delmenhorst, Germany, 27753
        • Staedtisches Kliniken Delmenhorst
      • Essen, Germany, D-45122
        • Universitaetsklinikum Essen
      • Essen, Germany, D-45239
        • Evangelisches Krankenhaus Essen Werden
      • Frankfurt, Germany, D-60590
        • Klinikum der J.W. Goethe Universitaet
      • Germering, Germany, 82110
        • Internistische Praxisgemeinschaft
      • Goslar, Germany, 38642
        • DR Herbert - Nieper Krankenhaus Goslar
      • Gottingen, Germany, D-37075
        • Universitaetsklinikum Goettingen
      • Hagen, Germany, D-58095
        • St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
      • Hamburg, Germany, D-20246
        • University Medical Center Hamburg - Eppendorf
      • Hamburg, Germany, D-20099
        • Asklepios Klinik St. Georg
      • Hamm, Germany, DOH-59063
        • Evangelische Krankenhaus Hamm
      • Heidelberg, Germany, 69115
        • Medizinische Universitaetsklinik und Poliklinik
      • Heidelberg, Germany, 69115
        • Universitätsklinikum Heidelberg
      • Heidelberg, Germany, D-69120
        • Ruprecht - Karls - Universitaet Heidelberg
      • Homburg, Germany, D-66424
        • Universitaetsklinikum des Saarlandes
      • Homburg, Germany, 66421
        • Medical University Hospital Homburg
      • Kaiserslautern, Germany, D-67653
        • Westpfalz-Klinikum GmbH
      • Karlsruhe, Germany, 76133
        • Staedtisches Klinikum Karlsruhe gGmbH
      • Karlsruhe, Germany, D-76137
        • St. Vincentius - Kliniken
      • Kempten, Germany, 87439
        • Klinikum Kempten Oberallgaeu
      • Kiel, Germany, D-24116
        • University Hospital Schleswig-Holstein - Kiel Campus
      • Krefeld, Germany, D-47805
        • Klinikum Krefeld GmbH
      • Langen, Germany, D-63225
        • Internistisches Fachaerzte Zentrum Langen
      • Lebach, Germany, 66822
        • Caritas - Krakenhaus Lebach
      • Leer, Germany, D-26789
        • Onkologische Schwerpunktpraxis - Leer
      • Lemgo, Germany, D-32657
        • Klinikum Lippe - Lemgo
      • Ludwigshafen am Rhein, Germany, D-67063
        • Klinikum der Stadt Ludwigshafen am Rhein
      • Mannheim, Germany, D-68305
        • III Medizinische Klinik Mannheim
      • Monchengladbach, Germany, D-41063
        • Hospital Maria-Hilf II
      • Muenchen, Germany, 80804
        • Krankenhaus Muenchen Schwabing
      • Muenster, Germany, D-48149
        • Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
      • Munich, Germany, D-81377
        • Klinikum der Universitaet Muenchen - Grosshadern Campus
      • Munich, Germany, D-81679
        • Haematologische Schwerpunktpraxis
      • Regensburg, Germany, 93047
        • Hematologische Onkologische Praxis
      • Regensburg, Germany, D-93042
        • Klinikum der Universitaet Regensburg
      • Remscheid, Germany, D-42859
        • Klinikum Remscheid GmbH
      • Russelsheim, Germany, 65428
        • Internistische Schwerpunktpraxis
      • Schwaebisch Hall, Germany, 74523
        • Diakonie - Krankenhaus
      • Siegen, Germany, D-57072
        • St. Marien - Krankenhaus Siegen GMBH
      • Siegen, Germany, D-57076
        • Kreiskrankenhaus Siegen
      • Stralsund, Germany, D-18410
        • Hanse-Klinikum Stralsund - Krankenhaus West
      • Straubing, Germany, 94315
        • Onkologische Schwerpunktpraxis - Straubing
      • Stuttgart, Germany, 70376
        • Robert-Bosch-Krankenhaus
      • Stuttgart, Germany, D-70174
        • Klinik fuer Onkologie - Katharinenhospital Stuttgart
      • Stuttgart, Germany, D-70176
        • Diakonie Klinikum Stuttgart
      • Stuttgart, Germany, D-70173
        • Haematologische Praxis
      • Trier, Germany, D-54290
      • Tuebingen, Germany, D-72076
        • Southwest German Cancer Center at Eberhard-Karls-University
      • Tuebingen, Germany, D-72072
        • Schwerpunktpraxis fuer Rheumatologie und Haematologie/Internistische Onkologie
      • Weiden, Germany, D-92637
        • Haematologische Praxis
      • Wuppertal, Germany, D-42283
        • Helios Kliniken Wuppertal University Hospital
      • Wuppertal, Germany, 42105
        • Praxis Fuer Haemotologie Und Internistischer Onkologie
      • Wurzburg, Germany, 97070
        • Hamatologisch - Onkologische Praxis Wurzburg
      • Wurzburg, Germany, D-97070
        • University Würzburg
  • Switzerland
      • Basel, Switzerland, CH 4051

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 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Newly diagnosed chronic phase chronic myelogenous leukemia (CML)

    • bcr-abl positive
    • No blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood
  • Availability of a HLA-identical sibling or unrelated donor

PATIENT CHARACTERISTICS:

Age

  • Any age

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Not specified

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No second malignancy requiring therapy
  • No evidence of disease-related symptoms or extramedullary disease (including hepatosplenomegaly)
  • No serious diseases that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior interferon

Chemotherapy

  • No prior chemotherapy other than hydroxyurea

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy

Surgery

  • Not specified

Other

  • Prior anagrelide allowed
  • No participation in another clinical trial

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression-free survival
Overall survival
Risk group-dependent survival
Hematologic, cytogenetic, and molecular response rates

Secondary Outcome Measures

Outcome Measure
Quality of life
Adverse drug effects

Collaborators and Investigators

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

Sponsor

Heidelberg University

Investigators

  • Study Chair: Ruediger Hehlmann, MD, III. Medizinische Klinik Mannheim

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

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

June 1, 2002

Primary Completion (Actual)

March 31, 2012

Study Completion (Actual)

March 31, 2017

Study Registration Dates

First Submitted

March 6, 2003

First Submitted That Met QC Criteria

March 6, 2003

First Posted (Estimate)

March 7, 2003

Study Record Updates

Last Update Posted (Actual)

May 3, 2018

Last Update Submitted That Met QC Criteria

May 2, 2018

Last Verified

November 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • III-MK-CML-IV
  • CDR0000271424 (Registry Identifier: PDQ (Physician Data Query))
  • EU-20248

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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