Imatinib Mesylate Plus Cytarabine in Treating Patients With Chronic Myelogenous Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: This phase II trial is studying giving imatinib mesylate together with cytarabine to see how well it works in treating patients with chronic phase chronic myelogenous leukemia.

Detailed Description
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OBJECTIVES: Determine the rate and duration of complete or major and minor cytogenetic responses after 6 and 12 months of treatment in patients with chronic phase chronic myelogenous leukemia treated with imatinib mesylate and cytarabine. Determine the rate and duration of complete hematologic responses after 6 and 12 months of treatment in patients treated with this regimen. Determine the rate of molecular response in patients with a complete cytogenetic response after 6 and 12 months of treatment with this regimen. Determine the pharmacokinetics of this regimen in these patients. Determine the safety of this regimen in these patients. OUTLINE: This is a nonrandomized, open-label, multicenter study. Patients receive oral imatinib mesylate on days 1-28 and cytarabine subcutaneously on days 15-28. Courses repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients are followed for 30-60 days. PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Official Title
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A Phase II Study To Determine The Anti-Leukemic Effects Of STI571 In Combination With Ara-C In Patients With Chronic Myelogenous Leukemia In Chronic Phase

Conditions
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Leukemia

Intervention / Treatment
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* Drug: cytarabine
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Cytogenetically confirmed chronic phase chronic myelogenous leukemia (CML) Less than 15% blasts in peripheral blood or bone marrow Less than 30% blasts and promyelocytes in peripheral blood or bone marrow Less than 20% basophils in blood or bone marrow Platelet count at least 100,000/mm^3 Philadelphia chromosome positive No more than 6 months since initial diagnosis No presence of leukemia beyond the bone marrow, blood, liver, or spleen (i.e., chloroma) Refused allogeneic stem cell transplantation as first-line therapy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST or ALT no greater than 2 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class III or IV heart disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for at least 3 months after study participation No other serious uncontrolled medical condition No history of noncompliance to medical regimens or potential unreliability PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior biologic therapy for CML Chemotherapy: No prior chemotherapy for CML except hydroxyurea Concurrent hydroxyurea to control blood counts during first 3 months of treatment allowed No other concurrent chemotherapy Endocrine therapy: No prior endocrine therapy for CML Radiotherapy: No prior radiotherapy for CML Surgery: Not specified Other: More than 28 days since prior investigational anticancer agents Prior anagrelide hydrochloride for CML allowed Concurrent anagrelide hydrochloride to control blood counts during first 3 months of treatment allowed No concurrent grapefruit juice or grapefruit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cytarabine/ Imatinib Mesylate<br> | Drug: cytarabine<br>* Once daily subcutaneous injection of Ara-C (Cytarabine) at a dose of 20 mg (10 mg or 5 mg if they have been dose reduced) per square meter of calculated body surface area, on days 15-28 of each sequential 28 day cycle<br>Drug: imatinib mesylate<br>* Once daily oral administration of STI571 (Imatinib Mesylate) at a dose of 400 mg for 12 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Rate of Major Cytogenetic Response at 6 Months | Cytogenetic response is defined in terms of the percentage of Philadelphia (Ph) chromosome. Major cytogenetic response is defined as 0-34% Ph-positive cells. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Rate of Complete Cytogenetic Response at 6 Months |  | 6 months | 
| The Rate of Complete and Major Cytogenetic Responses at 12 Months |  | 12 months | 
| The Rate of Minor Cytogenetic Responses at 6 and 12 Months |  | 6 and 12 months | 
| The Rate of Complete Hematologic Responses at 6 and 12 Months |  | 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic phase chronic myelogenous leukemia, Philadelphia chromosome positive chronic myelogenous leukemia