Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer

April 30, 2010 updated by: Virginia Commonwealth University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Ohio
      • Cleveland, Ohio, United States, 44106-5047
        • Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4283
        • Abramson Cancer Center of the University of Pennsylvania
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Massey Cancer Center at Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Virginia Commonwealth University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Steven Grant, MD, Massey Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2003

Study Registration Dates

First Submitted

July 8, 2003

First Submitted That Met QC Criteria

July 8, 2003

First Posted (Estimate)

July 9, 2003

Study Record Updates

Last Update Posted (Estimate)

May 3, 2010

Last Update Submitted That Met QC Criteria

April 30, 2010

Last Verified

April 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000310175
  • U01CA062502 (U.S. NIH Grant/Contract)
  • MCV-NCI-6013
  • MCV-VCU-1902
  • NCI-6013
  • CWRU-030323

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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