Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer - Full Text View

Sponsor:	Virginia Commonwealth University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Virginia Commonwealth University
ClinicalTrials.gov Identifier:	NCT00064285

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 I

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:

MedlinePlus related topics: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Leukemia

Drug Information available for: Alvocidib Flavopiridol Imatinib Imatinib mesylate

U.S. FDA Resources

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

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

National Cancer Institute (NCI)

Investigators

Study Chair:

Steven Grant, MD

Massey Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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
Flavopiridol
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 February 12, 2012