An Open-label, Non-randomized, Multicenter Phase I Study to Determine the Maximum Tolerated and / or Recommended Phase II Dose of Oral Mutant IDH1 (mIDH1) Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Efficacy in Patients With mIDH1-R132X Advanced Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 27
- 试验地点
- 13
- 主要终点
- Maximum tolerated dose (MTD) or RP2D of BAY1436032
研究概览
简要总结
To determine the maximum tolerated and / or recommended Phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients with advanced AML that harbors IDH1 mutation
- •Patients are relapsed from or refractory to at least 1 previous line of therapy
- •Good kidney and liver function
- •Male or female patients
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- •Women must have a negative serum pregnancy test within 7 days prior to the first dose of study drug or be surgically or biologically sterile or postmenopausal
排除标准
- •Previously treated with any prior mIDH1 targeted therapy
- •Extramedullary disease only
- •History of clinically significant or active cardiac disease
- •Active clinically significant infection
- •Unresolved chronic toxicity of previous AML treatment
- •Taking known strong cytochrome P450 (CYP) 2C8 inducers or inhibitors
- •Pregnancy or breast-feeding
研究组 & 干预措施
BAY1436032
Dose escalation:
Various doses of study drug will be tested on a small number of patients/dose with the goal of identifying the most appropriate dose(s) for further evaluation in dose expansion. The MTD of the study drug may or may not be identified. It is anticipated that 3-4 patients will be treated at each dose of study drug to be tested and that 15-20 total patients will be treated in this part of the trial.
Dose expansion:
Up to 2 different doses of study drug will be tested on up to 30 patients/dose with the goal of identifying the most appropriate RP2D for further clinical development. The doses to be evaluated in this part of the trial will be selected based on information obtained during dose escalation.
干预措施: BAY1436032 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) or RP2D of BAY1436032
时间窗: Within first 4 weeks of first dose
If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032
Number of participants with Adverse Events as a Measure of
时间窗: Up to 12 weeks
As a measure of safety and tolerability
次要结局
- AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)(Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days))
- Event-free survival (EFS)(Up to 12 weeks)
- Objective efficacy response(Up to 12 weeks)
- Duration of response(Up to 12 weeks)
- Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline(Up to 12 weeks)
- Cmax (maximum observed drug concentration in plasma after a single dose)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hour post-dose (each cycle is 28 days))
- AUC(0-8) (AUC from time 0 to 8 h after a single dose)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days))
- AUC(0-12) (AUC from time 0 to 12 h after a single dose)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days))
- Cmax,md (Cmax after multiple doses)(Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days))
- AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)(Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days))