Leukemia
Conditions
Keywords
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)
Brief summary
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
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.
Interventions
DRUGalvocidib
DRUGimatinib mesylate
Sponsors
National Cancer Institute (NCI)
Virginia Commonwealth University
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Countries
United States
Outcome results
None listed