STI571 ProspectIve RandomIzed Trial: SPIRIT
To test whether increasing the dose of imatinib or combining it with IFNalpha or ara-C increases the rate of molecular response (as measured by the decrease in BCR-ABL transcripts after 12 months of treatment) in patients with previously untreated CML in chronic phase.
To compare overall survival in a selected arm according to molecular response at 1 year from randomization with the reference arm.
Chronic Myeloid Leukemia
Drug: Imatinib mesylate 400 mg
Drug: Imatinib mesylate 600 mg
Drug: Imatinib 400 mg + Peg-Interferon
Drug: Imatinib mesylate 400 mg + Cytarabine
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Overall survival improvement [ Designated as safety issue: No ]
- Molecular response improvement at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Hematological, cytogenetic responses improvement [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Duration of responses improvement [ Designated as safety issue: No ]
- Survival without progression improvement
- Acceptable toxicity [ Designated as safety issue: Yes ]
|Study Start Date:||September 2003|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
|Experimental: Imatinib mesylate 400 mg||Drug: Imatinib mesylate 400 mg Drug: Imatinib mesylate 600 mg Drug: Imatinib 400 mg + Peg-Interferon Drug: Imatinib mesylate 400 mg + Cytarabine|
|Experimental: Imatinib mesylate 600 mg||Drug: Imatinib mesylate 400 mg Drug: Imatinib mesylate 600 mg Drug: Imatinib 400 mg + Peg-Interferon Drug: Imatinib mesylate 400 mg + Cytarabine|
|Experimental: Imatinib mesylate 400 mg +Peg interferon||Drug: Imatinib mesylate 400 mg Drug: Imatinib mesylate 600 mg Drug: Imatinib 400 mg + Peg-Interferon Drug: Imatinib mesylate 400 mg + Cytarabine|
|Experimental: Imatinib mesylate 400 mg +Cytarabine|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00219739
|Poitiers, France, 86021|
|Study Chair:||François GUILHOT, MD||Department of Oncology hematology and Cell therapy, University Hospital , 86021 Poitiers - FRANCE|