Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer

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 flavopiridol use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate with flavopiridol may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of flavopiridol and imatinib mesylate in treating patients with hematologic cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and recommended phase II dose of flavopiridol and imatinib mesylate in patients with Bcr/Abl+ hematological malignancies. Determine the toxic effects of this regimen in these patients. Determine the disease-related effects of this regimen in these patients. Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients. Correlate response to this regimen with mechanisms of imatinib mesylate resistance in patients previously treated with imatinib mesylate. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to percentage of blasts in the peripheral blood and bone marrow (less than 15% vs at least 15%) and recent myelosupressive treatment (no vs yes). Patients receive oral imatinib mesylate daily and flavopiridol IV over 1 hour on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of imatinib mesylate and flavopiridol 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. PROJECTED ACCRUAL: A total of 6-80 patients will be accrued for this study within 1 year.

Official Title
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Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies

Conditions
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Leukemia

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Chronic or accelerated phase chronic myelogenous leukemia (CML) with 1 of the following: Hematologic progression during prior imatinib mesylate treatment Less than a complete hematologic response after at least 3 months of prior imatinib mesylate treatment Less than a major cytogenetic response after at least 6 months of imatinib mesylate treatment (cytogenetic response documented by karyotype or fluorescence in situ hybridization [FISH]) Blastic phase CML* Acute lymphoblastic leukemia* Acute myeloid leukemia* NOTE: *Patients may be enrolled at presentation, in remission, or upon relapse Bcr/Abl+ in bone marrow confirmed by karyotype or FISH No known CNS malignancy PATIENT CHARACTERISTICS: Age 18 and over Performance status 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 and ALT no greater than 2.5 times ULN (5 times ULN if hepatic involvement suspected [stratum 2 only]) Renal Creatinine no greater than 2 times ULN Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Fertile patients must use effective contraception during and for 3 months after study participation No prior allergic reaction attributed to compounds of similar chemical or biological composition to study agents No other concurrent uncontrolled medical illness No ongoing or active infection No psychiatric illness or social situation that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-2 during the first course of study therapy unless clinically indicated for management of febrile neutropenia or thrombocytopenia Concurrent epoetin alfa allowed if started before study entry and it remains clinically appropriate Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other See Disease Characteristics Recovered from all prior therapy No other concurrent investigational or anticancer agents No concurrent combination antiretroviral therapy for HIV-positive patients

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
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: alvocidib|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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chronic phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)