Imatinib Mesylate and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Chronic Myelogenous Leukemia

Study Overview
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Brief Summary
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RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as 17-N-allylamino-17-demethoxygeldanamycin use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate with chemotherapy may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given together with imatinib mesylate in treating patients with chronic myelogenous leukemia.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with imatinib mesylate in patients with chronic myelogenous leukemia. Determine the pharmacokinetics of this regimen in these patients. OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). Patients receive oral imatinib mesylate on days 1-21 and 17-AAG IV over 1 hour on days 1, 4, 8, and 12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 17-AAG 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. Once the MTD is determined, an additional cohort of 6-10 patients receives treatment at the recommended phase II dose. PROJECTED ACCRUAL: Approximately 21-42 patients will be accrued for this study within 1.5 years.

Official Title
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Phase I Study Of The Combination Of 17-AAG And Imatinib Mesylate (Gleevec) In Patients With Blastic Phase, Accelerated Phase Of Chronic Mesylate Leukemia (CML) Or Patients With Chronic Phase CML Who Have Not Achieved A Cytogenetic Response With Imatinib Mesylate

Conditions
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Leukemia

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of chronic myelogenous leukemia, including any of the following phases: Blastic phase Greater than 30% blasts in the peripheral blood or bone marrow Previously untreated disease OR refractory to or relapsed after most recent therapy Accelerated phase, defined by 1 of the following: At least 15, but less than 30%, blasts in the peripheral blood or bone marrow At least 30% blasts and promyelocytes in the peripheral blood or bone marrow Greater than 20% peripheral blood basophilia Chronic phase No major cytogenetic response (less than 65% Philadelphia chromosome negative) after 12 months of prior imatinib mesylate therapy Philadelphia chromosome positive by routine cytogenetics PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 3 months Hematopoietic Not specified Hepatic Bilirubin no greater than 1.5 mg/dL ALT and AST no greater than 2.5 times upper limit of normal Renal Creatinine less than 1.5 mg/dL Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known allergy to eggs Able to swallow pills No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other concurrent uncontrolled medical illness PRIOR CONCURRENT THERAPY: Biologic therapy No prior stem cell transplantation Chemotherapy More than 4 weeks since prior chemotherapy (except hydroxyurea or anagrelide) (at least 6 weeks for nitrosoureas or mitomycin) Endocrine therapy Not specified Radiotherapy More than 4 weeks since prior radiotherapy Surgery No prior liver, kidney, or lung transplantation More than 14 days since prior major surgery (e.g., thoracotomy or intra-abdominal surgery) Other Prior imatinib mesylate administered within the past 4 weeks is allowed No concurrent tacrolimus or cyclosporine as immunosuppressive agents No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent agents that alter CYP3A4 activity, including any of the following: Grapefruit juice Ketoconazole Fluconazole Itraconazole Erythromycin Clarithromycin Cimetidine Terfenadine Astemizole HIV protease inhibitors (e.g., indinavir and nelfinavir)

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: imatinib mesylate|nan|
|Drug: tanespimycin|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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blastic phase chronic myelogenous leukemia, Philadelphia chromosome positive chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia