STI571 ProspectIve RandomIzed Trial: SPIRIT

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Drug: Imatinib mesylate 400 mg
* Drug: Imatinib mesylate 600 mg
* Drug: Imatinib 400 mg + Peg-Interferon
* Drug: Imatinib mesylate 400 mg + Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years of age Patients with Bcr-Abl positive CML in chronic phase. Patients within 14 weeks of diagnosis and previously untreated for CML except for hydroxyurea and/or anagrelide. No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly ECOG performance score of 0-2 acceptable hepatic, renal, and cardiac function Informed consent signed up Exclusion Criteria: Depressive syndrome not controlled Uncontrolled medical illnesses. Women with childbearing potential and male patients who are unwilling or unable to use an adequate method to avoid pregancy for the entire period of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib mesylate 400 mg<br> | Drug: Imatinib mesylate 400 mg<br> <br> Drug: Imatinib mesylate 600 mg<br> <br> Drug: Imatinib 400 mg + Peg-Interferon<br> <br> Drug: Imatinib mesylate 400 mg + Cytarabine<br> <br> |
| Experimental: Imatinib mesylate 600 mg<br> | Drug: Imatinib mesylate 400 mg<br> <br> Drug: Imatinib mesylate 600 mg<br> <br> Drug: Imatinib 400 mg + Peg-Interferon<br> <br> Drug: Imatinib mesylate 400 mg + Cytarabine<br> <br> |
| Experimental: Imatinib mesylate 400 mg +Peg interferon<br> | Drug: Imatinib mesylate 400 mg<br> <br> Drug: Imatinib mesylate 600 mg<br> <br> Drug: Imatinib 400 mg + Peg-Interferon<br> <br> Drug: Imatinib mesylate 400 mg + Cytarabine<br> <br> |
| Experimental: Imatinib mesylate 400 mg +Cytarabine<br> | Drug: Imatinib mesylate 400 mg<br> <br> Drug: Imatinib mesylate 600 mg<br> <br> Drug: Imatinib 400 mg + Peg-Interferon<br> <br> Drug: Imatinib mesylate 400 mg + Cytarabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival improvement |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular response improvement at 1 year |  | 1 year | 
| Hematological, cytogenetic responses improvement |  | 1 year | 
| Duration of responses improvement |  |  | 
| Survival without progression improvement |  |  | 
| Acceptable toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CML, Imatinib, Interferon, Cytarabine