A Phase 1b Open-label Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Administration of Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 17
- 试验地点
- 19
- 主要终点
- Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.
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 99 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
Blinatumomab and AMG 404
干预措施: Blinatumomab (Drug)
Blinatumomab and AMG 404
干预措施: AMG 404 (Drug)
Blinatumomab and AMG 404
干预措施: Dexamethasone Premedication (Drug)
结局指标
主要结局
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
时间窗: Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days
Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.
Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)
时间窗: Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days
A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that: * results in death, * immediately life-threatening, * requires in-patient hospitalization or prolongation of existing hospitalization, * results in persistent or significant disability/incapacity, * is a congenital anomaly/birth defect, and/or * other medically important serious AE. AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages.
次要结局
- Maximum Observed Concentration (Cmax) of AMG 404(Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion))
- Time to Cmax (Tmax) of AMG 404(Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion))
- Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404(Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion))
- Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)(Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days)
- Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles(Up to approximately 274 days)
- Steady-state Concentrations (Css) of Blinatumomab(Cohort 1: C1D1 and D8 (predose, 2 to 24 h postdose), and D11, D18 and D29; C2D1 (predose, 2 to 24 h postdose) and D29. Cohort 2a: C1D3 and D10 (predose, 2 to 48 h postdose), and D29, D30 and D31; C2D1 (predose, 2 to 24 h postdose), D13 and D29)
- Number of Participants With Incidences of Anti-AMG 404 Antibodies(Up to approximately 274 days)
- Percentage of Participants Who Achieved CR(Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days)
- Number of Participants With Incidences of Anti-Blinatumomab Antibodies(Up to approximately 274 days)
- Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles(Up to approximately 274 days)