Phase III Randomized Study of Imatinib Mesylate Alone or With Interferon alfa or Low-Dose Cytarabine Versus Interferon alfa Standard Therapy Followed By Allogeneic Stem Cell Transplantation in Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information
Alternate Title
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
Basic Trial Information
| Phase | Type | Status | Age | Protocol IDs |
|---|
| Phase III | Treatment | Active | Any age | III-MK-CML-IV
EU-20248, NCT00055874 |
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.
Entry 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
Prior/Concurrent Therapy:
Biologic therapy
Chemotherapy
- No prior chemotherapy other than hydroxyurea
Endocrine therapy
Radiotherapy
Surgery
Other
- Prior anagrelide allowed
- No participation in another clinical trial
Patient Characteristics:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
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
Expected Enrollment
1600
A total of 1,600 patients (400 per treatment arm) will be accrued for this study within 4-5 years.
Outcomes
Primary Outcome(s)Overall survival
Risk group-dependent survival
Progression-free survival
Hematologic, cytogenetic, and molecular response rates
Secondary Outcome(s)Adverse drug effects
Quality of life
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.
Published ResultsHehlmann R, Lauseker M, Jung-Munkwitz S, et al.: Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-α in newly diagnosed chronic myeloid leukemia. J Clin Oncol 29 (12): 1634-42, 2011.[PUBMED Abstract]
Burchert A, Müller MC, Kostrewa P, et al.: Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia. J Clin Oncol 28 (8): 1429-35, 2010.[PUBMED Abstract]
Saussele S, Lauseker M, Gratwohl A, et al.: Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood 115 (10): 1880-5, 2010.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
III Medizinische Klinik Mannheim
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| Ruediger Hehlmann, MD, Protocol chair | | |
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Trial Sites
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| Germany |
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Aachen |
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| | Krankenhaus / Klinikum Krefeld |
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| | Michaela Johnen, MD | |
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Aurich |
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| | Kreiskrankenhaus Aurich |
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| | Langer, MD | |
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Email:
langer@kkh-aurich.de |
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Bad Hersfeld |
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| | Kreiskrankenhaus |
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| | P J Majunke, MD | |
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Berlin |
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| | Gemeinschaftspraxis fuer Haematologie und Internistische Onkologie |
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| | Friedrich Ludwig, MD | |
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Email:
onkopraxis-lmu@GMX.de |
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| | Haematologisch-Onkologische Schwerpunktpraxis |
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| | Ilona Blau, MD | |
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| | Schwerpunktpraxis fuer Haematologie und Internistische Onkologie |
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| | Christian Sperling, MD | |
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| | St. Hedwig Krankenhaus |
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| | Christian Boewer, MD | |
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Bielefeld |
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| | Onkologische Schwerpunktpraxis Bielefeld |
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| | Marianne Just, MD | |
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Bonn |
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| | Augustinum |
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| | Karl Grips, MD | |
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Brandenburg |
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| | Hamatologische Sprechstunde |
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| | Fischer-Lampsatis, MD | |
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Bremen |
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| | Praxis Dres. F.& G. Doering |
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| | Gabriele Doering, MD | |
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Delmenhorst |
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| | Staedtisches Kliniken Delmenhorst |
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| | Funke, MD | |
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Essen |
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| | Evangelisches Krankenhaus Essen Werden |
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| | Franz-Karl Baur, MD | |
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| | Universitaetsklinikum Essen |
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| | Ulrich Duehrsen | |
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Frankfurt |
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| | Klinikum der J.W. Goethe Universitaet |
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| | Dieter Hoelzer, MD, PhD | |
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Germering |
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| | Internistische Praxisgemeinschaft |
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| | Johann Mittermueller, MD | |
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Goslar |
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| | DR Herbert - Nieper Krankenhaus Goslar |
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| | Andreas Hoyer, MD | |
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Gottingen |
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| | Universitaetsklinikum Goettingen |
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| | Claudia Binder, MD, PhD | |
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Hagen |
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| | St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH |
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| | Hartmut Eimermacher, MD | |
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Hamburg |
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| | Asklepios Klinik St. Georg |
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| | Rutjes, MD | |
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| | University Medical Center Hamburg - Eppendorf |
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| | Maike de Wit, MD, PhD | |
|
| | Peter Mundhenk, MD | |
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Hamm |
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| | Evangelische Krankenhaus Hamm |
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| | Leopold Balleisen, MD | |
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Email:
LBalleisen@evkhamm.de |
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Heidelberg |
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| | Medizinische Universitaetsklinik und Poliklinik |
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| | Anthony Ho, MD, PhD | |
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Email:
anthony_ho@med.uni-heidelberg.de |
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| | Ruprecht - Karls - Universitaet Heidelberg |
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| | Stefan Fruehauf, MD | |
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| | Universitatsklinikum Heidelberg |
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| | Elke Brants | |
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Homburg |
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| | Medical University Hospital Homburg |
|
| | Hans Pees, MD | |
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| | Universitaetsklinikum des Saarlandes |
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| | Michael Pfreundschuh, MD | |
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Email:
michael.pfreundschuh@uniklinik-saarland.de |
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Kaiserslautern |
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| | Westpfalz-Klinikum GmbH |
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| | Katja Buhl | |
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Karlsruhe |
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| | St. Vincentius - Kliniken |
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| | Gerhard Goeckel, MD | |
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Email:
gerhard.goeckel@vincentius-ka.de |
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| | J. Mezger, MD | |
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| | Staedtisches Klinikum Karlsruhe gGmbH |
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| | Contact Person | |
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Kempten |
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| | Klinikum Kempten Oberallgaeu |
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| | Gatter, MD | |
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Kiel |
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| | University Hospital Schleswig-Holstein - Kiel Campus |
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| | Robert Schoch, MD | |
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Krefeld |
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| | Klinikum Krefeld GmbH |
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| | Sabine Helmer, MD | |
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Langen |
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| | Internistisches Fachaerzte Zentrum Langen |
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| | Andreas Koehler, MD | |
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Lebach |
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| | Caritas - Krakenhaus Lebach |
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| | Harald Jost, MD | |
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Leer |
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| | Onkologische Schwerpunktpraxis - Leer |
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| | Lothar Mueller, MD | |
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Email:
Lothar.Mueller@onkologie-leer.de |
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Lemgo |
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| | Klinikum Lippe - Lemgo |
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| | Contact Person | |
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Ludwigshafen am Rhein |
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| | Klinikum der Stadt Ludwigshafen am Rhein |
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| | Henrich, MD | |
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Email:
henrichd@klilu.de |
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Mannheim |
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| | III Medizinische Klinik Mannheim |
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| | Michael Schatz, MD | |
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Monchengladbach |
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| | Hospital Maria-Hilf II |
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| | Lange, MD | |
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Muenchen |
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| | Krankenhaus Muenchen Schwabing |
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| | Christof Fischer, MD | |
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Muenster |
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| | Haematologisch - Onkologische Gemeinschaftspraxis - Muenster |
|
| | Juergen Wehmeyer, MD | |
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Email:
wehmeyer@onkologie-muenster.de |
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Munich |
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| | Haematologische Schwerpunktpraxis |
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| | Helmut Hitz, MD | |
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| | Klinikum der Universitaet Muenchen - Grosshadern Campus |
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| | Torsten Haferlach, MD | |
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Regensburg |
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| | Hematologische Onkologische Praxis |
|
| | Robert Dengler, MD | |
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Email:
robert.dougler@t-online.de |
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| | Klinikum der Universitaet Regensburg |
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| | Stefan Krause, MD | |
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Remscheid |
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| | Klinikum Remscheid GmbH |
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| | Arthur Wehmeier, MD | |
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| | F. Meierkord, MD | |
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Russelsheim |
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| | Internistische Schwerpunktpraxis |
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| | M. Baldus, MD | |
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Schwaebisch Hall |
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| | Diakonie - Krankenhaus |
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| | Thomas Geer, MD | |
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Email:
tgeer@diaksha.de |
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Siegen |
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| | Kreiskrankenhaus Siegen |
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| | Schulz, MD | |
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| | St. Marien - Krankenhaus Siegen GMBH |
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| | Winfried Gassmann, MD | |
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Stralsund |
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| | Hanse-Klinikum Stralsund - Krankenhaus West |
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| | Thomas Heinz Ittel, MD | |
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Email:
medizinische.klinik@klinikum-stralsund.de |
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Straubing |
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| | Onkologische Schwerpunktpraxis - Straubing |
|
| | Matthias Demandt, MD | |
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Stuttgart |
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| | Diakonie Klinikum Stuttgart |
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| | Else Heidemann, MD | |
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| | Haematologische Praxis |
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| | Gregor Springer, MD | |
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| | Klinik fuer Onkologie - Katharinenhospital Stuttgart |
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| | Hans-Guenther Mergenthaler, MD | |
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Email:
h.mergenthaler@katharinehospital.de |
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| | Robert-Bosch-Krankenhaus |
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| | Walter Aulitzky, MD | |
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Email:
walter.aulitzky@rbk.de |
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Trier |
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| | Bernhard Rendenbach, MD | |
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Email:
info@straurenlau.de |
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Tuebingen |
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| | Schwerpunktpraxis fuer Rheumatologie und Haematologie/Internistische Onkologie |
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| | Swen Jacki, MD | |
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| | Southwest German Cancer Center at Eberhard-Karls-University |
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| | Tim Henrik Brummendorf, MD | |
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Email:
tim.bruemmendorf@med.uni-tuebingen.de |
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Weiden |
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| | Haematologische Praxis |
|
| | Johann Weiss, MD | |
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| |
Wuppertal |
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| | Helios Kliniken Wuppertal University Hospital |
|
| | Aruna Raghavachar, MD, PhD | |
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Email:
araghavachar@wuppertal.helios-kliniken.de |
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| | Praxis Fuer Haemotologie Und Internistischer Onkologie |
|
| | Werner Fett, MD | |
| |
Email:
fett-onkologe@t-online.de |
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Wurzburg |
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| | Hamatologisch - Onkologische Praxis Wurzburg |
|
| | Rudolf Schlag, MD | |
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| | University Wurzburg |
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| | M. Goebeler, MD | |
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| Switzerland |
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| |
Basel |
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|
|
| | Walter Weber-Stadelmann, MD | |
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Email:
cancer@bluewin.ch |
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| Registry Information |
|
| 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 |
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| Trial Start Date | | 2002-06-28 |
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| Trial Completion Date | | 2016-12-31 (estimated) |
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| Registered in ClinicalTrials.gov | | NCT00055874 |
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| Date Submitted to PDQ | | 2003-01-22 |
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| Information Last Verified | | 2011-11-09 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.
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