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
- Conditions
- Leukemia
- Registration Number
- NCT00055874
- Lead Sponsor
- Heidelberg University
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1551
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Progression-free survival Hematologic, cytogenetic, and molecular response rates Risk group-dependent survival Overall survival
- Secondary Outcome Measures
Name Time Method Adverse drug effects Quality of life
Trial Locations
- Locations (63)
Kreiskrankenhaus Aurich
🇩🇪Aurich, Germany
Krankenhaus / Klinikum Krefeld
🇩🇪Aachen, Germany
Haematologisch-Onkologische Schwerpunktpraxis
🇩🇪Berlin, Germany
St. Hedwig Krankenhaus
🇩🇪Berlin, Germany
Kreiskrankenhaus
🇩🇪Bad Hersfeld, Germany
Schwerpunktpraxis fuer Haematologie und Internistische Onkologie
🇩🇪Berlin, Germany
Gemeinschaftspraxis fuer Haematologie und Internistische Onkologie
🇩🇪Berlin, Germany
Onkologische Schwerpunktpraxis Bielefeld
🇩🇪Bielefeld, Germany
Hamatologische Sprechstunde
🇩🇪Brandenburg, Germany
Praxis Dres. F.& G. Doering
🇩🇪Bremen, Germany
Augustinum
🇩🇪Bonn, Germany
Staedtisches Kliniken Delmenhorst
🇩🇪Delmenhorst, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Klinikum der J.W. Goethe Universitaet
🇩🇪Frankfurt, Germany
Evangelisches Krankenhaus Essen Werden
🇩🇪Essen, Germany
DR Herbert - Nieper Krankenhaus Goslar
🇩🇪Goslar, Germany
Internistische Praxisgemeinschaft
🇩🇪Germering, Germany
St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
🇩🇪Hagen, Germany
Universitaetsklinikum Goettingen
🇩🇪Gottingen, Germany
Evangelische Krankenhaus Hamm
🇩🇪Hamm, Germany
Universitatsklinikum Heidelberg
🇩🇪Heidelberg, Germany
University Medical Center Hamburg - Eppendorf
🇩🇪Hamburg, Germany
Asklepios Klinik St. Georg
🇩🇪Hamburg, Germany
Medizinische Universitaetsklinik und Poliklinik
🇩🇪Heidelberg, Germany
Medical University Hospital Homburg
🇩🇪Homburg, Germany
Ruprecht - Karls - Universitaet Heidelberg
🇩🇪Heidelberg, Germany
Westpfalz-Klinikum GmbH
🇩🇪Kaiserslautern, Germany
Staedtisches Klinikum Karlsruhe gGmbH
🇩🇪Karlsruhe, Germany
Internistisches Fachaerzte Zentrum Langen
🇩🇪Langen, Germany
St. Vincentius - Kliniken
🇩🇪Karlsruhe, Germany
Klinikum Kempten Oberallgaeu
🇩🇪Kempten, Germany
Klinikum Krefeld GmbH
🇩🇪Krefeld, Germany
University Hospital Schleswig-Holstein - Kiel Campus
🇩🇪Kiel, 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
Hospital Maria-Hilf II
🇩🇪Monchengladbach, Germany
III Medizinische Klinik Mannheim
🇩🇪Mannheim, Germany
Haematologische Schwerpunktpraxis
🇩🇪Munich, Germany
Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
🇩🇪Muenster, Germany
Krankenhaus Muenchen Schwabing
🇩🇪Muenchen, Germany
Klinikum der Universitaet Muenchen - Grosshadern Campus
🇩🇪Munich, Germany
Klinikum der Universitaet Regensburg
🇩🇪Regensburg, Germany
Klinikum Remscheid GmbH
🇩🇪Remscheid, Germany
Hematologische Onkologische Praxis
🇩🇪Regensburg, Germany
Diakonie - Krankenhaus
🇩🇪Schwaebisch Hall, Germany
Kreiskrankenhaus Siegen
🇩🇪Siegen, Germany
St. Marien - Krankenhaus Siegen GMBH
🇩🇪Siegen, Germany
Hanse-Klinikum Stralsund - Krankenhaus West
🇩🇪Stralsund, Germany
Haematologische Praxis
🇩🇪Weiden, Germany
Robert-Bosch-Krankenhaus
🇩🇪Stuttgart, Germany
Onkologische Schwerpunktpraxis - Straubing
🇩🇪Straubing, Germany
Klinik fuer Onkologie - Katharinenhospital Stuttgart
🇩🇪Stuttgart, Germany
Schwerpunktpraxis fuer Rheumatologie und Haematologie/Internistische Onkologie
🇩🇪Tuebingen, Germany
Diakonie Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Hamatologisch - Onkologische Praxis Wurzburg
🇩🇪Wurzburg, Germany
Southwest German Cancer Center at Eberhard-Karls-University
🇩🇪Tuebingen, Germany
Praxis Fuer Haemotologie Und Internistischer Onkologie
🇩🇪Wuppertal, Germany
University Wurzburg
🇩🇪Wurzburg, Germany
Helios Kliniken Wuppertal University Hospital
🇩🇪Wuppertal, Germany
Universitaetsklinikum des Saarlandes
🇩🇪Homburg, Germany
Internistische Schwerpunktpraxis
🇩🇪Russelsheim, Germany