A Phase 1 First-in-human Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 330 Administered as Continuous Intravenous Infusion in Subjects With Myeloid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 95
- 试验地点
- 10
- 主要终点
- Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
The purpose of this First-in-Human Phase 1 study is to determine if AMG 330 given as a continuous IV infusion is safe and tolerable in adult subjects that have myeloid malignancies, and to determine the maximum tolerated dose and/or a biologically active dose. The study will be conducted in multiple sites and test increasing doses of AMG 330. The safety of subjects will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
研究组 & 干预措施
Group 1: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
干预措施: AMG 330 (Drug)
Group 2: Minimal Residual Disease Positive (MRD+) AML
干预措施: AMG 330 (Drug)
Group 3: Myelodysplastic syndrome (MDS)
干预措施: AMG 330 (Drug)
Group 4: R/R AML with alternative pretreatment
干预措施: AMG 330 (Drug)
Group 5: R/R AML with alternative dose schedule
干预措施: AMG 330 (Drug)
结局指标
主要结局
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
时间窗: Day 1 until 30 days after last dose. Median duration of treatment was: Group 1 - 29.0 days; Group 2 - 29.0 days; Group 3 - 49.50 days; Group 4 - 23.50 days
The severity of TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. The general guideline for assessment ranged from Grade 1 to 5, with higher grades indicating a worse outcome, and included: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death.
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
时间窗: Day 1 to Day 14
A participant was not DLT-evaluable if they dropped out before completion of the DLT window (14 days) for reasons other than an adverse event related to study drug or the participant had not received investigational product (IP) treatment for at least 14 days at the target dose for a 3- or 4-week cycle or at least 7 days at a target dose for a 2- week cycle. Furthermore, following drug interruptions, if a participant was unable to complete 2 repeat cycles for reasons other than DLT, the participant was not DLT evaluable.
次要结局
- Response Rate in Participants With R/R AML(From first dose of IP (Day 1) until the end of study, up to approximately 6 months)
- Event-free Survival(From first dose of IP (Day 1) until the end of study, up to approximately 6 months)
- 28 Day Infusion Duration: CL of AMG 330(Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days))
- Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation(Baseline until the end of study, up to approximately 6 months)
- Response Rate in Participants With MRD-positive AML(From first dose of IP (Day 1) until the end of study, up to approximately 6 months)
- Response Rate in Participants With MDS(From first dose of IP (Day 1) until the end of study, up to approximately 6 months)
- Duration of Response(From first dose of IP (Day 1) until the end of study, up to approximately 6 months)
- 14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 330(14 day infusion duration: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days))
- 14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330(Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days))
- 28 Day Infusion Duration: Css After End of Infusion of AMG 330(Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days))
- 14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330(Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days))
- 28 Day Infusion Duration: Vz of AMG 330(Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 day))
- Time to Response(From first dose of IP (Day 1) until the end of study, up to approximately 6 months)
- 14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330(Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days))
- Overall Survival(Baseline until the end of study, up to approximately 6 months)
- 28 Day Infusion Duration: t1/2 z of AMG 330(Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days))