A Phase I, Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics and Efficacy of HMPL-306 in Patients of Relapsed/Refractory Myeloid Leukemia/Neoplasms With IDH1 and/or IDH2 Mutation
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Safety and tolerability: Incidence of adverse events
研究概览
简要总结
Phase I, multicenter study to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in Patients of Relapsed/Refractory Myeloid Leukemia/Neoplasms with IDH1 and/or IDH2 Mutation.
详细描述
The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in Patients of Relapsed/Refractory Myeloid Leukemia/Neoplasms with IDH1 and/or IDH2 Mutation. The first stage of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of HMPL-306 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second stage of the study is a dose expansion phase where three cohorts of patients will receive HMPL-306 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose.
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
- •≥18 years of age;
- •Signed Informed Consent Form;
- •Relapsed/refractory Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia(CMML) and others myeloid neoplasm;
- •IDH1 and/or IDH2 mutated disease status as assessed by local laboratory;
- •Cooperative Oncology Group (ECOG) performance status of 0-2;
- •Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
排除标准
- •Previously treated with any prior IDH1 inhibitor, IDH2 inhibitor, or IDH1/IDH2 double-targeted therapy and had disease progression during treatment;
- •with known involvement or clinical symptoms of central nervous system (CNS);
- •Patients who have undergone HSCT within 60 days;
- •Without adequate liver or kidney function;
- •With known infection with active hepatitis B or C;
- •With known infection with human immunodeficiency virus (HIV);
- •History of clinically significant or active cardiac disease;
- •Active clinically significant infection;
- •Taking known strong cytochrome P450 (CYP) 2C8 inducers or inhibitors;
- •Pregnancy or breast-feeding.
研究组 & 干预措施
HMPL-306
HMPL-306 administered continuously as a single agent orally every day in a 28-day cycle.
干预措施: HMPL-306 (Drug)
结局指标
主要结局
Safety and tolerability: Incidence of adverse events
时间窗: Baseline up to the last patient has completed the 24 weeks of treatment
Incidence of adverse events.
Maximum tolerated dosage (MTD) and/or recommended phase 2 dosage (RP2D)
时间窗: Baseline up to the last patient has completed the 24 weeks of treatment
Measured by adverse event profile.
次要结局
- Cmax (Cycle 1 Day 1) of HMPL-306(Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start)
- AUC(0-24) (Cycle 1 Day 1) of HMPL-306(Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start)
- AUC(0-tlast) (Cycle 1 Day 1) of HMPL-306(Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start)
- Objective Response Rate (ORR)(Baseline up to the last patient has completed the 24 weeks of treatment)
- Duration of response (DOR)(Baseline up to the last patient has completed the 24 weeks of treatment)
- Progression-free survival (PFS)(Baseline up to the last patient has completed the 24 weeks of treatment)
- Overall survival (OS)(Baseline up to the last patient has completed the 24 weeks of treatment)