Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies
- 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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Steven Grant, MD
Massey Cancer Center
United States: Food and Drug Administration
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University||Cleveland, Ohio 44106|
|Massey Cancer Center at Virginia Commonwealth University||Richmond, Virginia 23298-0037|