A Phase IB, Open-Label Study to Determine the Safety and Pharmacokinetics of Twice Daily Oral Dosing of PKC412 Administered in Combinations Sequentially and Concomitantly With Daunorubicin and Cytarabine for Standard Induction Therapy, and High Dose Cytarabine for Consolidation in Patients With Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 5
- 主要终点
- Complete Response (CR) rate
研究概览
简要总结
RATIONALE: PKC412 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of daunorubicin and cytarabine by making cancer cells more sensitive to the drugs. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining PKC412 with chemotherapy may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best way to give PKC412 when given either after or together with daunorubicin and cytarabine in treating patients with newly diagnosed acute myeloid leukemia.
详细描述
OBJECTIVES:
Primary
- Determine the safety and tolerability of PKC412 administered sequentially or concurrently with induction chemotherapy comprising daunorubicin and cytarabine followed by consolidation therapy comprising high-dose cytarabine in patients with newly diagnosed acute myeloid leukemia.
- Compare the pharmacokinetics of these regimens in these patients.
Secondary
- Determine the efficacy of these regimens, in terms of response rate, disease-free survival, and overall survival, in these patients.
- Correlate genetic variation in drug metabolism genes, leukemia genes, and drug target genes with response in patients treated with these regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（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
研究组 & 干预措施
PKC412 administered sequentially
twice daily oral dosing of PKC412 administered sequentially
干预措施: midostaurin (Drug)
PKC412 administered concomitantly
PKC412 administered concomitantly with standard induction daunorubicin and cytarabine therapy followed by high-dose consolidation therapy with cytarabine
干预措施: cytarabine (Drug)
PKC412 administered concomitantly
PKC412 administered concomitantly with standard induction daunorubicin and cytarabine therapy followed by high-dose consolidation therapy with cytarabine
干预措施: daunorubicin hydrochloride (Drug)
PKC412 administered concomitantly
PKC412 administered concomitantly with standard induction daunorubicin and cytarabine therapy followed by high-dose consolidation therapy with cytarabine
干预措施: midostaurin (Drug)
结局指标
主要结局
Complete Response (CR) rate
时间窗: cycle 1, day 14, cycle day 21 - 28, end of each cycle
cycle = between 28 days and 42 days in duration
次要结局
- Overall survival by FLT3 mutation status(time of death of any cause(FLT# - minthly))
- CR rate by FLT3 mutation and treatment arm(CR:cycle 1, day 14, cycle day 21 - 28, end of each cycle, FLT3: monthly)