A Phase III Prospective Randomized Comparison of Imatinib at a Dose of 400mg in Combination With Peg-Interferon-alpha2a (Peg-IFNa2a) or Cytarabine (Ara-C)Versus Imatinib at a Dose of 600mg Versus Imatinib a Dose of 400mg for Previously Untreated Chronic Myelogenous Leukemia (CML) in Chronic Phase
Imatinib at 400 mg daily has emerged as the preferred therapy for newly diagnosed CML
patients who do not undergo allogeneic stem cell transplant.
A phase III randomized study, comparing imatinib at 400 mg per day to interferon plus
cytarabine in newly diagnosed chronic phase CML patients enrolled 1106 patients from June
2000 to January 2001. 553 patients were randomized to each treatment. For comparative
purposes, at 6 months, 75% of patients randomized to imatinib obtained a major cytogenetic
response with 51% complete responses. Despite these impressive results, only a minority of
patients treated with imatinib in this study achieved a molecular remission. When analyzed
by log reduction in Bcr-Abl transcript levels using quantitative RT-PCR, 39% of patients
achieved a 3-log reduction in Bcr-Abl levels, but only 13% and 3% achieved a 4- and 5-log
reduction, respectively.2 To improve upon these results, various groups have tried higher
doses of imatinib, and combinations of imatinib with interferon alpha or cytarabine. Each of
these studies has used cytogenetic responses as the major endpoint.
Each of these therapies has increased toxicity as compared to 400 mg of imatinib alone and
the rates of molecular remissions have not been reported.
Thus the purpose of this study is to first determine whether higher doses of imatinib or
combining Imatinib with interferon or Ara-C would result in higher rates of molecular
responses and if so, in better survival.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival improvement
François GUILHOT, MD
Department of Oncology hematology and Cell therapy, University Hospital , 86021 Poitiers - FRANCE
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)