Imatinib Mesylate and Decitabine in Treating Patients With Chronic Myelogenous Leukemia

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

Detailed Description
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OBJECTIVES: I. Determine the duration of response and response rate in patients with accelerated or blastic phase chronic myelogenous leukemia treated with imatinib mesylate and decitabine. II. Determine the survival rate of patients treated with this regimen. III. Determine the toxicity of this regimen in these patients. IV. Determine the effects of this regimen on gene methylation in the leukemic cells of these patients. OUTLINE: Patients are stratified according to prior exposure to imatinib mesylate (yes vs no). Patients receive oral imatinib mesylate daily and decitabine IV over 1 hour daily, 5 days per week, for 2 consecutive weeks. Courses repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 20-80 patients (10-40 per stratum) will be accrued for this study within 20 months.

Official Title
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Phase II Study of Imatinib Mesylate (Gleevec, STI-571) (NSC#716051) and Decitabine (5-AZA-2'-Deoxycitidine) (NSC#127716), in Chronic Myelogenous Leukemia in Accelerated and Blastic Phases

Conditions
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Accelerated Phase Chronic Myelogenous Leukemia, Blastic Phase Chronic Myelogenous Leukemia, Childhood Chronic Myelogenous Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Relapsing Chronic Myelogenous Leukemia

Intervention / Treatment
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* Drug: imatinib mesylate
* Drug: decitabine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed chronic myelogenous leukemia Philadelphia chromosome positive by cytogenetics OR fluorescent in situ hybridization Accelerated or non-lymphoid blastic phase Performance status - ECOG 0-2 Bilirubin no greater than 2 times upper limit of normal (ULN) AST no greater than 2 times ULN Creatinine less than 2.0 mg/dL Normal cardiac function No New York Heart Association class III or IV heart disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior decitabine At least 2 weeks since other prior chemotherapy (unless there is evidence of rapidly progressive disease) and recovered Concurrent hydroxyurea allowed during the first 2 courses of study therapy in patients with rapidly progressing disease Prior imatinib mesylate allowed Patients who received at least 4 weeks of prior imatinib mesylate must have failed therapy, as evidenced by resistance after 8 weeks or disease progression No concurrent grapefruit or grapefruit juice
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: Treatment (imatinib mesylate, decitabine)<br>Patients receive oral imatinib mesylate daily and decitabine IV over 1 hour daily, 5 days per week, for 2 consecutive weeks. Courses repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity. | Drug: imatinib mesylate<br>* Given orally<br>* Other names: Glivec;Drug: decitabine<br>* Given IV<br>* Other names: DAC;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete and partial response |  | 6 months | 
| Hematologic improvement |  | Up to 1 year | 
| Duration of response |  | Date of documented response until relapse, assessed up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 |  | Up to 4 years |