Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00064285
Recruitment Status : Completed
First Posted : July 9, 2003
Last Update Posted : May 3, 2010
National Cancer Institute (NCI)
Information provided by:
Virginia Commonwealth University

July 8, 2003
July 9, 2003
May 3, 2010
June 2003
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Complete list of historical versions of study NCT00064285 on Archive Site
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Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer
Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies

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.


  • 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.

Phase 1
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Drug: alvocidib
  • Drug: imatinib mesylate
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • See Disease Characteristics


  • 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])


  • Creatinine no greater than 2 times ULN


  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia


  • 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


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


  • Not specified

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • See Disease Characteristics
  • Recovered from all prior therapy
  • No other concurrent investigational or anticancer agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
U01CA062502 ( U.S. NIH Grant/Contract )
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National Cancer Institute
Virginia Commonwealth University
National Cancer Institute (NCI)
Study Chair: Steven Grant, MD Massey Cancer Center
Virginia Commonwealth University
April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP