NCT00030108已完成1 期
Phase I Trial and Pharmacokinetic Study of BMS-247550 (NSC 710428, Ixabepilone), an Epothilone B Analog, in Pediatric Patients With Refractory Solid Tumors and Leukemias
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose and dose-limiting toxicity of ixabepilone
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone in treating young patients with relapsed or refractory solid tumors or leukemia.
详细描述
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of ixabepilone in young patients with refractory solid tumors (closed to accrual as of 10/4/2007) or relapsed or refractory leukemia.
- Determine the toxicity spectrum of this drug in these patients.
- Determine the plasma pharmacokinetics of this drug in these patients.
- Determine the pharmacodynamics of this drug in these patients.
- Assess the nerve growth factor levels, before and after the initiation of this drug, as a potential surrogate marker for the development of peripheral neuropathy in these patients.
Secondary
- Determine the response of patients treated with this drug.
- Compare the tolerability, toxicity profile, MTD, DLT, pharmacokinetics, and pharmacodynamics of this drug in young patients treated on this study vs adults with solid tumors (closed to accrual as of 10/4/2007) treated on the ongoing Medicine Branch, NCI, phase I study.
- Assess the safety and tolerability of ixabepilone at the solid tumor MTD (expanded leukemia cohort).
- Evaluate the plasma pharmacokinetics of in young patients with refractory or relapsed leukemia.
- Evaluate the extent of tubulin polymerization in leukemic blasts at baseline after treatment with ixabepilone ex-vivo.
- Compare the effects of tubulin polymerization in leukemic blasts with ixabepilone versus paclitaxel ex-vivo with an without the presence of a potent P-glycoprotein inhibitor.
- Evaluate the activity known drug transporters in drug-resistant leukemias in leukemic blasts.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 2 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Meets 1 of the following criteria:
- •Histologically confirmed solid tumor (closed to accrual as of 10/4/2007) that relapsed after or failed to respond to front-line curative therapy and for which no other potentially curative treatment options exist
- •Curative therapy may include surgery, radiotherapy, chemotherapy, or any combination of these modalities
- •Eligible tumor types include, but are not limited to, the following:
- •Rhabdomyosarcoma
- •Other soft tissue sarcomas
- •Ewing's sarcoma family of tumors
- •Osteosarcoma
- •Neuroblastoma
- •Wilms' tumor
- •Hepatic tumors
- •Germ cell tumors
- •Primary brain tumors
- •Histologic confirmation may be waived for brain stem or optic glioma
- •Diagnosis of relapsed or refractory leukemia
- •Patients with refractory or second or greater relapsed leukemia must have > 25% blasts in the bone marrow (M3 bone marrow) with or without active extramedullary disease (except for leptomeningeal disease)
- •Relapsed after or failed to respond to frontline curative therapy and no other potentially curative therapy (e.g., radiotherapy, chemotherapy, or any combination of these modalities) exists
- •Patients with acute promyelocytic leukemia must be refractory to treatment with retinoic acid and arsenic trioxide
- •Patients with Philadelphia chromosome positive chronic myelogenous leukemia must be refractory to imatinib
- •No active CNS leukemia (CNS3)
- •PATIENT CHARACTERISTICS:
- •2 to 18 (solid tumor patients [closed to accrual as of 10/4/2007])
- •1 to 21 (leukemia patients)
- •Performance status:
- •For patients age 11 to 21:
- •Karnofsky 50-100%
- •For patients age 1 to 10:
- •Lansky 50-100%
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •Platelet count at least 100,000/mm^3 (20,000/mm^3 for leukemia patients)
- •Hemoglobin ≥ 8.0 g/dL
- •Bilirubin less than 1.5 times upper limit of normal (ULN)
- •SGOT and SGPT less than 2.5 times ULN
- •No hepatic dysfunction that would preclude study
- •Creatinine normal for age OR
- •Creatinine clearance at least 60 mL/min
- •No renal dysfunction that would preclude study
- •No known severe prior hypersensitivity reaction to agents containing Cremophor EL
- •No clinically significant unrelated systemic illness (e.g., serious infections or other organ dysfunction) that would preclude study
- •No grade 2 or greater preexisting sensory neuropathy
- •More than 2 month since prior and no concurrent evidence of graft vs host disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Recovered from all therapy-related acute toxic effects (leukemia patients only)
- 另有 42 项未显示
排除标准
- 未提供
结局指标
主要结局
Maximum tolerated dose and dose-limiting toxicity of ixabepilone
Toxicity spectrum
Plasma pharmacokinetics
Pharmacodynamics
Nerve growth factor levels before and after drug administration
次要结局
- Objective tumor response
- Tubulin polymerization in PBMCs prior to the start of the infusion, just before the end of the infusion, 5 hours after the end of the infusion and before the start of the infusion on day 2 of the ixabepilone on course 1
研究者
研究点 (2)
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