Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00064285
First received: July 8, 2003
Last updated: April 30, 2010
Last verified: April 2010
  Purpose

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 Intervention Phase
Leukemia
Drug: alvocidib
Drug: imatinib mesylate
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Enrollment: 22
Study Start Date: June 2003
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064285

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Ohio
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
Cleveland, Ohio, United States, 44106-5047
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Virginia
Massey Cancer Center at Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Study Chair: Steven Grant, MD Massey Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute
ClinicalTrials.gov Identifier: NCT00064285     History of Changes
Other Study ID Numbers: CDR0000310175, U01CA062502, MCV-NCI-6013, MCV-VCU-1902, NCI-6013, CWRU-030323
Study First Received: July 8, 2003
Last Updated: April 30, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Virginia Commonwealth University:
chronic phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)

Additional relevant MeSH terms:
Leukemia
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Hematologic Diseases
Alvocidib
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Growth Inhibitors
Growth Substances
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014