Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer

Virginia Commonwealth University (VCU)

Status and phase

Completed

Phase 1

Conditions

Leukemia

Treatments

Drug: imatinib mesylate

Drug: alvocidib

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00064285

U01CA062502 (U.S. NIH Grant/Contract)

MCV-VCU-1902

CWRU-030323

CDR0000310175

MCV-NCI-6013

NCI-6013

Details and patient eligibility

About

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.

Enrollment

22 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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