Acute Myeloid Leukemia Clinical Trial
Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer
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.
Full 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.
Eligibility 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
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 4 Locations for this study
Baltimore Maryland, 21231, United States
Cleveland Ohio, 44106, United States
Philadelphia Pennsylvania, 19104, United States
Richmond Virginia, 23298, United States
How clear is this clinincal trial information?
Please confirm you are a US based health care provider:
Yes, I am a health care Provider No, I am not a health care providerSign Up Now.
Take Control of Your Disease Journey.
Sign up now for expert patient guides, personalized treatment options, and cutting-edge insights that can help you push for the best care plan.