A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy
试验速览
- 阶段
- 2 期
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Overall safety profile of PHA-739358 by type, severity, timing, and relatedness of adverse events and laboratory abnormalities
研究概览
简要总结
RATIONALE: PHA-739358 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well PHA-739358 works in treating patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy.
详细描述
OBJECTIVES:
- Explore the clinical efficacy of PHA-739358, in terms of hematological response lasting ≥ 4 weeks, in patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy.
- Explore the safety profile of this drug in these patients.
- Explore the pharmacokinetic profile of this drug and its N-oxide metabolite PHA-816359 in plasma.
- Explore the modulation of histone H3 and CRKL phosphorylation after PHA-739358 administration.
- Explore the relationship between plasma drug levels and the modulation of histone H3 and CRKL phosphorylation.
- Explore the clinical efficacy of this drug, in terms of cytogenetic response in bone marrow.
- Explore response depending on status of T315I mutation in BCR-ABL kinase.
OUTLINE: This is a pilot, open-label, multicenter study.
Patients receive PHA-739358 IV over 6 hours on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients benefitting from treatment may receive additional courses at the discretion of the investigator.
Patients undergo blood collection and bone marrow biopsies periodically for pharmacologic and biomarker correlative studies.
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
- 未提供
排除标准
- 未提供
结局指标
主要结局
Overall safety profile of PHA-739358 by type, severity, timing, and relatedness of adverse events and laboratory abnormalities
Antileukemic response in terms of complete hematological response, no evidence of leukemia, or return to chronic phase
Pharmacokinetics of this drug and its N-oxide metabolite PHA-816359 by measuring their plasma concentration at different times after dosing
Changes in histone H3 and CRKL phosphorylation
Complete, partial, or minor cytogenetic response in bone marrow
Correlation between changes in degree of histone H3 and CRKL phosphorylation and concurrent PHA-739358 concentrations and/or hematological response
次要结局
未报告次要终点