Cladribine, Cytarabine, and Imatinib Mesylate in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Blastic Phase Chronic Myelogenous Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cladribine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cladribine and cytarabine together with imatinib mesylate may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate when given together with cladribine and cytarabine in treating patients with refractory or relapsed acute myeloid leukemia or blastic phase chronic myelogenous leukemia.

Detailed Description
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OBJECTIVES: Determine the safety and feasibility of cladribine, cytarabine, and imatinib mesylate in patients with refractory or relapsed acute myeloid leukemia or blastic phase chronic myelogenous leukemia. Determine the maximum tolerated dose of imatinib mesylate in patients treated with this regimen. Correlate the expression of c-kit and the presence of c-kit mutations with clinical response in patients treated with this regimen. Correlate the in vitro inhibitory effects of imatinib mesylate and cytarabine on the proliferation and survival of leukemic cells with clinical response in patients treated with this regimen. OUTLINE: This is a dose-escalation study of imatinib mesylate. Patients receive oral imatinib mesylate once daily on days 1-15 and cladribine IV over 2 hours and cytarabine IV over 4 hours on days 3-7. Patients also receive filgrastim (G-CSF) subcutaneously on days 2-7. Treatment repeats every 15 days for 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed periodically for up to 1 year. PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study.

Official Title
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A Phase I Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Refractory or Relapsed Leukemias

Conditions
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Leukemia

Intervention / Treatment
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* Biological: filgrastim
* Drug: cladribine
* Drug: cytarabine
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of acute myeloid leukemia (AML) or blastic phase chronic myelogenous leukemia (CML) Refractory AML defined as any of the following: Failure to achieve complete response (CR) after 2 courses of induction chemotherapy Persistent bone marrow blasts > 40% after 1 course of induction chemotherapy Relapse of disease within 3 months since CR Relapsed AML defined as the following: Any evidence of disease recurrence after CR (early relapse occurs within 3-12 months and late relapse occurs > 12 months later) No acute promyelocytic leukemia (AML-M3 FAB subgroup) PATIENT CHARACTERISTICS: Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin ≤ 2.0 mg/dL AST ≤ 2.5 times upper limit of normal No known chronic liver disease (e.g., chronic active hepatitis or cirrhosis) Renal Creatinine < 2.5 mg/dL (if 2.0-2.5 mg/dL, glomerular filtration rate must be measured and dose of cytarabine adjusted if necessary) Cardiovascular No New York Heart Association grade III-IV heart disease No congestive heart failure No myocardial infarction within the past 6 months Ejection fraction ≥ 30% Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 3 months after completion of study treatment No uncontrolled systemic active infection No known HIV infection No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs No history of other curatively treated malignancy except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy No other concurrent biologic agents Chemotherapy See Disease Characteristics No other concurrent chemotherapy Endocrine therapy No concurrent birth control pills Other More than 1 week since any prior investigational agent No other concurrent investigational agents or therapies No other concurrent anticancer agents No concurrent therapeutic anticoagulation with warfarin Low molecular weight heparin or heparin allowed for therapeutic anticoagulation Mini-dose warfarin (e.g., 1 mg per day) allowed for prophylaxis of central venous catheter thrombosis

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: cladribine|nan|
|Drug: cytarabine|nan|
|Drug: imatinib mesylate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia, adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult acute megakaryoblastic leukemia (M7), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia without maturation (M1), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), blastic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia