Arsenic Trioxide and Imatinib Mesylate 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. Combining chemotherapy with imatinib mesylate may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combining arsenic trioxide with imatinib mesylate in treating patients who have chronic phase chronic myelogenous leukemia.

Detailed Description
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OBJECTIVES: Determine the safety and tolerability of arsenic trioxide and imatinib mesylate in patients with resistant chronic phase chronic myelogenous leukemia. Determine potential dose-limiting toxic effects in patients treated with this regimen. Determine the pharmacokinetics of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral imatinib mesylate once daily and arsenic trioxide IV over 1-2 hours on days 1-5 of week 1 and then twice weekly. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 18-24 patients (at least 6 patients for phase I and at least 12 patients for phase II) will be accrued for this study .

Official Title
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A Phase I/II Study To Determine The Safety, Tolerability, And Anti-Leukemic Effects of Trisenox (Arsenic Trioxide) In Combination With Gleevec (STI571) In Patients With Resistant Chronic Myelogenous Leukemia In Chronic Phase

Conditions
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Leukemia

Intervention / Treatment
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* Drug: arsenic trioxide
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Cytogenetically confirmed Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia, meeting one of the following criteria: Chronic phase Less than 15% blasts in peripheral blood or marrow Less than 30% blasts and promyelocytes in peripheral blood or marrow Less than 20% basophils in blood or marrow Platelet count at least 100,000/mm^3 (unless therapy related) No progressive (increase of at least 10 cm in any 4 of the past 24 weeks) or existing (greater than 10 cm) splenomegaly Complete hematologic response (CHR) No immature myeloid cells in peripheral blood No increased basophils in peripheral blood WBC less than upper limit of normal (ULN) Platelet count less than ULN No major (less than 35% Ph+) or complete (0% Ph+) cytogenetic response after at least 6 months of imatinib mesylate Loss of prior major cytogenetic response or failure to achieve major cytogenetic response PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Bilirubin less than 1.5 times ULN AST or ALT less than 2.5 times ULN Renal Creatinine less than 1.5 times ULN Cardiovascular No New York Heart Association grade III or IV congestive heart failure No untreated symptomatic cardiac ischemia No underlying cardiac arrhythmia, including but not limited to any of the following: Conduction abnormality/atrioventricular heart block Nodal/junctional arrhythmia/dysrhythmia Sinus bradycardia or tachycardia Supraventricular tachycardia Ventricular arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 methods of effective barrier contraception during and for 3 months after study Electrolyte levels (especially potassium and magnesium) normal (CHR patients) No history of noncompliance that would preclude study participation No other concurrent serious, uncontrolled medical condition No grade 2 or greater neuropathy PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other More than 14 days since prior therapy except hydroxyurea, anagrelide hydrochloride, or imatinib mesylate More than 28 days since prior investigational agents No concurrent grapefruit or grapefruit juice

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: arsenic trioxide|nan|
|Drug: imatinib mesylate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Satey and Tolerability |  |  | 
| Dose-limiting toxicity |  |  | 
| Pharmacokinetics |  |  | 

 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