Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 |
| Enrollment: | 22 |
| Study Start Date: | June 2003 |
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 |
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| 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 | |
| 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 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 May 23, 2013