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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00055874
• Other study ID #: III-MK-CML-IV
• Secondary ID: CDR0000271424EU-
• Status: Completed
• Phase: Phase 3
• Start date: June 2002
• Est. completion date: March 31, 2017

Study information

• Verified date: November 2011
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1551
• Est. completion date: March 31, 2017
• Est. primary completion date: March 31, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• recombinant interferon alfa

Drug:
• cytarabine

• hydroxyurea

• imatinib mesylate

Procedure:
• allogeneic bone marrow transplantation

• autologous bone marrow transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
Germany	Krankenhaus / Klinikum Krefeld	Aachen
Germany	Kreiskrankenhaus Aurich	Aurich
Germany	Kreiskrankenhaus	Bad Hersfeld
Germany	Gemeinschaftspraxis fuer Haematologie und Internistische Onkologie	Berlin
Germany	Haematologisch-Onkologische Schwerpunktpraxis	Berlin
Germany	Schwerpunktpraxis fuer Haematologie und Internistische Onkologie	Berlin
Germany	St. Hedwig Krankenhaus	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	Evangelisches Krankenhaus Essen Werden	Essen
Germany	Universitaetsklinikum Essen	Essen
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Internistische Praxisgemeinschaft	Germering
Germany	DR Herbert - Nieper Krankenhaus Goslar	Goslar
Germany	Universitaetsklinikum Goettingen	Gottingen
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	Ruprecht - Karls - Universitaet Heidelberg	Heidelberg
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Medical University Hospital Homburg	Homburg
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	St. Vincentius - Kliniken	Karlsruhe
Germany	Staedtisches Klinikum Karlsruhe gGmbH	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	Monchengladbach
Germany	Krankenhaus Muenchen Schwabing	Muenchen
Germany	Haematologisch - Onkologische Gemeinschaftspraxis - Muenster	Muenster
Germany	Haematologische Schwerpunktpraxis	Munich
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Hematologische Onkologische Praxis	Regensburg
Germany	Klinikum der Universitaet Regensburg	Regensburg
Germany	Klinikum Remscheid GmbH	Remscheid
Germany	Internistische Schwerpunktpraxis	Russelsheim
Germany	Diakonie - Krankenhaus	Schwaebisch Hall
Germany	Kreiskrankenhaus Siegen	Siegen
Germany	St. Marien - Krankenhaus Siegen GMBH	Siegen
Germany	Hanse-Klinikum Stralsund - Krankenhaus West	Stralsund
Germany	Onkologische Schwerpunktpraxis - Straubing	Straubing
Germany	Diakonie Klinikum Stuttgart	Stuttgart
Germany	Haematologische Praxis	Stuttgart
Germany	Klinik fuer Onkologie - Katharinenhospital Stuttgart	Stuttgart
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	Schwerpunktpraxis fuer Rheumatologie und Haematologie/Internistische Onkologie	Tuebingen
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Germany	Haematologische Praxis	Weiden
Germany	Helios Kliniken Wuppertal University Hospital	Wuppertal
Germany	Praxis Fuer Haemotologie Und Internistischer Onkologie	Wuppertal
Germany	Hamatologisch - Onkologische Praxis Wurzburg	Wurzburg
Germany	University Wurzburg	Wurzburg

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Countries where clinical trial is conducted

Germany,  Switzerland, 

References & Publications (3)

Burchert A, Müller MC, Kostrewa P, Erben P, Bostel T, Liebler S, Hehlmann R, Neubauer A, Hochhaus A. Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid — View Citation

Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Müller MC, Pletsch N, Proetel U, Haferlach C, Schlegelberger B, Balleisen L, Hänel M, Pfirrmann M, Krause SW, Nerl C, Pralle H, Gratwohl A, Hossfeld DK, Hasford J, Hochhaus A, Saussele S. Tolerability-ad — View Citation

Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, Kolb HJ, Ho AD, Falge C, Holler E, Schlimok G, Zander AR, Arnold R, Kanz L, Dengler R, Haferlach C, Schlegelberger B, Pfirrmann M, Müller MC, Schnittger S, Leitner A, Pletsch N, Hoc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival
Primary	Risk group-dependent survival
Primary	Progression-free survival
Primary	Hematologic, cytogenetic, and molecular response rates
Secondary	Adverse drug effects
Secondary	Quality of life