Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI MCV-NCI-6013 MCV-VCU-1902, NCI-6013, CWRU-030323, NCT00064285, 6013

Objectives

1. Determine the maximum tolerated dose and recommended phase II dose of flavopiridol and imatinib mesylate in patients with Bcr/Abl+ hematological malignancies.
2. Determine the toxic effects of this regimen in these patients.
3. Determine the disease-related effects of this regimen in these patients.
4. Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients.
5. Correlate response to this regimen with mechanisms of imatinib mesylate resistance in patients previously treated with imatinib mesylate.

Entry 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

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

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

Expected Enrollment

A total of 6-80 patients will be accrued for this study within 1 year.

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.

Trial Contact Information

Trial Lead Organizations

Virginia Commonwealth University Massey Cancer Center

Steven Grant, MD, Protocol chair		Ph: 804-828-5211

Registry Information
Official Title		Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies
Trial Start Date		2003-06-13
Registered in ClinicalTrials.gov		NCT00064285
Date Submitted to PDQ		2003-05-30
Information Last Verified		2005-12-03
NCI Grant/Contract Number		CA62502, CA70095, CA99168

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