Clinical trial NCT00064285: Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer
Official title: Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Keywords: 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)
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-07-09
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Richmond
country: United States
facility: Massey Cancer Center at Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Massey Cancer Center
name: Steven Grant, MD
role: STUDY_CHAIR
References: