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Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies

Phase 1
18 Years
Not Enrolling

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Trial Information

Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies


- 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

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.

Inclusion Criteria


- Diagnosis of 1 of the following:

- Chronic or accelerated phase chronic myelogenous leukemia (CML) with 1 of the

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Steven Grant, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Massey Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2003

Completion Date:

Related Keywords:

  • Leukemia
  • 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)
  • Leukemia
  • Hematologic Neoplasms



Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University Cleveland, Ohio  44106
Massey Cancer Center at Virginia Commonwealth University Richmond, Virginia  23298-0037