Phase I Study Of The Combination Of 17-AAG And Imatinib Mesylate (Gleevec) In Patients With Blastic Phase, Accelerated Phase Of Chronic Mesylate Leukemia (CML) Or Patients With Chronic Phase CML Who Have Not Achieved A Cytogenetic Response With Imatinib Mesylate
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 2
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 17-N-allylamino-17-demethoxygeldanamycin use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate with chemotherapy may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given together with imatinib mesylate in treating patients with chronic myelogenous leukemia.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with imatinib mesylate in patients with chronic myelogenous leukemia.
- Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).
Patients receive oral imatinib mesylate on days 1-21 and 17-AAG IV over 1 hour on days 1, 4, 8, and 12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 17-AAG 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. Once the MTD is determined, an additional cohort of 6-10 patients receives treatment at the recommended phase II dose.
研究设计
- 研究类型
- Interventional
- 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 chronic myelogenous leukemia, including any of the following phases:
- •Blastic phase
- •Greater than 30% blasts in the peripheral blood or bone marrow
- •Previously untreated disease OR refractory to or relapsed after most recent therapy
- •Accelerated phase, defined by 1 of the following:
- •At least 15, but less than 30%, blasts in the peripheral blood or bone marrow
- •At least 30% blasts and promyelocytes in the peripheral blood or bone marrow
- •Greater than 20% peripheral blood basophilia
- •Chronic phase
- •No major cytogenetic response (less than 65% Philadelphia chromosome negative) after 12 months of prior imatinib mesylate therapy
- •Philadelphia chromosome positive by routine cytogenetics
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •At least 3 months
- •Hematopoietic
- •Not specified
- •Bilirubin no greater than 1.5 mg/dL
- •ALT and AST no greater than 2.5 times upper limit of normal
- •Creatinine less than 1.5 mg/dL
- •Cardiovascular
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No known allergy to eggs
- •Able to swallow pills
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No other concurrent uncontrolled medical illness
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •No prior stem cell transplantation
- •Chemotherapy
- •More than 4 weeks since prior chemotherapy (except hydroxyurea or anagrelide) (at least 6 weeks for nitrosoureas or mitomycin)
- •Endocrine therapy
- •Not specified
- •Radiotherapy
- •More than 4 weeks since prior radiotherapy
- •No prior liver, kidney, or lung transplantation
- •More than 14 days since prior major surgery (e.g., thoracotomy or intra-abdominal surgery)
- •Prior imatinib mesylate administered within the past 4 weeks is allowed
- •No concurrent tacrolimus or cyclosporine as immunosuppressive agents
- •No other concurrent investigational agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent agents that alter CYP3A4 activity, including any of the following:
- 另有 10 项未显示
排除标准
- 未提供