Phase I Study Of Flavopiridol In Combination With Imatinib Mesylate (STI571, Gleevec) In Bcr/Abl+ Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 4
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •18 and over
- •Performance status
- •Life expectancy
- •Not specified
- •Hematopoietic
- •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
- •Cardiovascular
- •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 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
- •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
排除标准
- 未提供