A Phase 1/1b/2a, 3-Part, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Ascending Doses of AZD5991 Monotherapy and in Combination With Venetoclax in Subjects With Relapsed or Refractory Haematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- maximum tolerated dose
研究概览
简要总结
This study is a multicenter, open-label, nonrandomized, sequential group, dose-escalation study to assess safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ascending doses of AZD5991 in subjects with relapsed or refractory hematologic malignancies Part 1 of the study is monotherapy dose escalation. Closed November 2020 Part 2 of the study is monotherapy expansion groups for relapsed/refractory chronic lymphocytic leukaemia (CLL), AML/ myelodysplastic syndromes (MDS), and multiple myeloma (MM). Closed November 2020 Part 3 is a sequential, dose-escalation study of the combination of AZD5991 and venetoclax in subjects with relapsed/refractory AML
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 85 Years（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
AZD5991 + venetoclax
Dose escalation - multiple dose levels
干预措施: AZD5991 + Venetoclax (Drug)
Monotherapy AZD5991 expansion
Dose expansion
干预措施: AZD5991 (Drug)
Monotherapy AZD5991
Dose escalation - multiple dose levels
干预措施: AZD5991 (Drug)
结局指标
主要结局
maximum tolerated dose
时间窗: Minimum observation period is 28 days for the maximum dose cohort
Dose limiting toxicities
时间窗: Minimum observation period is 28 days per cohort
Incidence of Adverse Events
时间窗: At every treatment and follow up visit until disease progression. Expected to be for up to 12 months
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
次要结局
- Objective response rate (ORR)(From time of first dose until discontinuation of AZD5991 monotherapy and AZD5991+venetoclax expected to be for up to 12 months)
- Duration of response (DOR)(From time of first dose until discontinuation of AZD5991 monotherapy and AZD5991+venetoclax expected to be for up to 12 months)
- Maximum observed plasma concentration of AZD5991 monotherapy and AZD5991+venetoclax(Predose and through 24 hours postdose)
- Area under the concentration-time curve for plasma concentrations of AZD5991 monotherapy and AZD5991+venetoclax(Predose and through 24 hours postdose)
- Progression-free survival (PFS)(From time of first dose until first observation of progression expected to be for up to 12 months)
- Complete remission rate (CRR)(From time of first dose until discontinuation of AZD5991 monotherapy and AZD5991+venetoclax expected to be for up to 12 months)