Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies
18 Years
N/A
Both
Leukemia
Trial Information
Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Steven Grant, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Massey Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000310175
NCT ID:
NCT00064285
Start Date:
June 2003
Completion Date:
Related Keywords:
- Leukemia
- 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)
- Leukemia
- Hematologic Neoplasms
Name | Location |
|---|---|
| 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 |
