Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer

Sponsor

Virginia Commonwealth University (Other)

Overall Status

Completed

CT.gov ID

NCT00064285

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

5.5

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: alvocidib Drug: imatinib mesylate	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Non-Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231
2	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio	United States	44106-5047
3	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
4	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia	United States	23298