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

NCT ID: NCT00055874

Last Updated: 2018-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1551 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-06-30
• Study Completion Date: 2017-03-31

Brief Summary

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.

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.

Conditions

Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

recombinant interferon alfa

Intervention Type: BIOLOGICAL

cytarabine

Intervention Type: DRUG

hydroxyurea

Intervention Type: DRUG

imatinib mesylate

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

autologous bone marrow transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Dr. h.c. R. Hehlmann

Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ruediger Hehlmann, MD

Role: STUDY_CHAIR

III. Medizinische Klinik Mannheim

Locations

Krankenhaus / Klinikum Krefeld

Aachen, , Germany

Kreiskrankenhaus Aurich

Aurich, , Germany

Kreiskrankenhaus

Bad Hersfeld, , Germany

St. Hedwig Krankenhaus

Berlin, , Germany

Haematologisch-Onkologische Schwerpunktpraxis

Berlin, , Germany

Schwerpunktpraxis fuer Haematologie und Internistische Onkologie

Berlin, , Germany

Gemeinschaftspraxis fuer Haematologie und Internistische Onkologie

Berlin, , Germany

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, , Germany

Augustinum

Bonn, , Germany

Hamatologische Sprechstunde

Brandenburg, , Germany

Praxis Dres. F.& G. Doering

Bremen, , Germany

Staedtisches Kliniken Delmenhorst

Delmenhorst, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Evangelisches Krankenhaus Essen Werden

Essen, , Germany

Klinikum der J.W. Goethe Universitaet

Frankfurt, , Germany

Internistische Praxisgemeinschaft

Germering, , Germany

DR Herbert - Nieper Krankenhaus Goslar

Goslar, , Germany

Universitaetsklinikum Goettingen

Göttingen, , Germany

St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

Hagen, , Germany

Asklepios Klinik St. Georg

Hamburg, , Germany

University Medical Center Hamburg - Eppendorf

Hamburg, , Germany

Evangelische Krankenhaus Hamm

Hamm, , Germany

Medizinische Universitaetsklinik und Poliklinik

Heidelberg, , Germany

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Ruprecht - Karls - Universitaet Heidelberg

Heidelberg, , Germany

Medical University Hospital Homburg

Homburg, , Germany

Universitaetsklinikum des Saarlandes

Homburg, , Germany

Westpfalz-Klinikum GmbH

Kaiserslautern, , Germany

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, , Germany

St. Vincentius - Kliniken

Karlsruhe, , Germany

Klinikum Kempten Oberallgaeu

Kempten, , Germany

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, , Germany

Klinikum Krefeld GmbH

Krefeld, , Germany

Internistisches Fachaerzte Zentrum Langen

Langen, , Germany

Caritas - Krakenhaus Lebach

Lebach, , Germany

Onkologische Schwerpunktpraxis - Leer

Leer, , Germany

Klinikum Lippe - Lemgo

Lemgo, , Germany

Klinikum der Stadt Ludwigshafen am Rhein

Ludwigshafen am Rhein, , Germany

III Medizinische Klinik Mannheim

Mannheim, , Germany

Hospital Maria-Hilf II

Mönchengladbach, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Haematologische Schwerpunktpraxis

Munich, , Germany

Krankenhaus Muenchen Schwabing

München, , Germany

Haematologisch - Onkologische Gemeinschaftspraxis - Muenster

Münster, , Germany

Hematologische Onkologische Praxis

Regensburg, , Germany

Klinikum der Universitaet Regensburg

Regensburg, , Germany

Klinikum Remscheid GmbH

Remscheid, , Germany

Internistische Schwerpunktpraxis

Rüsselsheim am Main, , Germany

Diakonie - Krankenhaus

Schwäbisch Hall, , Germany

St. Marien - Krankenhaus Siegen GMBH

Siegen, , Germany

Kreiskrankenhaus Siegen

Siegen, , Germany

Hanse-Klinikum Stralsund - Krankenhaus West

Stralsund, , Germany

Onkologische Schwerpunktpraxis - Straubing

Straubing, , Germany

Robert-Bosch-Krankenhaus

Stuttgart, , Germany

Haematologische Praxis

Stuttgart, , Germany

Klinik fuer Onkologie - Katharinenhospital Stuttgart

Stuttgart, , Germany

Diakonie Klinikum Stuttgart

Stuttgart, , Germany

Trier, , Germany

Schwerpunktpraxis fuer Rheumatologie und Haematologie/Internistische Onkologie

Tübingen, , Germany

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, , Germany

Haematologische Praxis

Weiden, , Germany

Praxis Fuer Haemotologie Und Internistischer Onkologie

Wuppertal, , Germany

Helios Kliniken Wuppertal University Hospital

Wuppertal, , Germany

Hamatologisch - Onkologische Praxis Wurzburg

Würzburg, , Germany

University Wurzburg

Würzburg, , Germany

Basel, , Switzerland

Countries

Germany; Switzerland

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Other Identifiers

CDR0000271424

Identifier Type: REGISTRY

Identifier Source: secondary_id

EU-20248

Identifier Type: -

Identifier Source: secondary_id

III-MK-CML-IV

Identifier Type: -

Identifier Source: org_study_id