NCT03190278进行中（未招募）1 期
Phase I, Open Label Dose Escalation and Dose-Expansion Study to Evaluate the Safety, Expansion, Persistence, and Clinical Activity of UCART123 (Allogeneic Engineered T-cells Expressing Anti-CD123 Chimeric Antigen Receptor), Administered in Patients With Relapsed/Refractory Acute Myeloid Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 29
- 试验地点
- 8
- 主要终点
- Incidence of adverse events (AE)/serious adverse events (SAE)/Dose Limiting Toxicities (DLT) [Safety and Tolerability]
研究概览
简要总结
Phase I, open-label, dose-escalation and dose-expansion study evaluating the safety and efficacy of Universal Chimeric Antigen Receptor T-cell (UCART) targeting the Cluster of Differentiation 123 (CD123) in patients with relapsed/refractory acute myeloid leukemia (AML). The purpose of this study is to evaluate the safety and clinical activity of Universal Chimeric Antigen Receptor T-cells targeting CD123 (UCART123v1.2) and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with relapsed or primary refractory AML (as defined in World Health Organization [WHO] criteria) with ≥5% bone marrow blasts
- •Patients with CD123+ blast cells (verified by flow cytometry)
- •Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of ≤1
- •Adequate organ function, including bone marrow, renal, hepatic, pulmonary, and cardiac function based on the last assessment performed within screening period
- •(Dose-escalation) Identified donor and transplant strategy prior to lymphodepletion (LD)
- •Other criteria may apply
排除标准
- •Patients with acute promyelocytic leukemia (APL) or central nervous system (CNS) Leukemia
- •Previous investigation gene or cell therapy (including CAR)
- •> 1 prior allogeneic stem cell transplantations (SCTs)
- •Prior treatment with rituximab or other anti-cluster of differentiation 20 (anti-CD20) therapy within 3 months
- •Any known active or uncontrolled infection
- •Other criteria may apply
研究组 & 干预措施
Dose Escalation
Experimental
UCART123v1.2 tested at several dose levels with different lymphodepletion regimens to establish Maximum Tolerated Dose (MTD) and identify Recommended Phase 2 Dose (RP2D)
Dose Expansion: UCART123v1.2 administered at the RP2D determined from the dose escalation phase
干预措施: UCART123v1.2 (Biological)
结局指标
主要结局
Incidence of adverse events (AE)/serious adverse events (SAE)/Dose Limiting Toxicities (DLT) [Safety and Tolerability]
时间窗: 24 Months
Safety of UCART123v1.2 - Incidence, nature, and severity of AE and SAEs throughout the study
Dose escalation and expansion part: Occurrence of DLTs
时间窗: Up to Day 28 post last UCART123v1.2 infusion
次要结局
- Progression Free Survival(From the first day of study treatment to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24)
- Pharmacokinetic (PK) Analysis: Standard PK Analysis will be completed to obtain Maximum plasma concentration (Cmax)(alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose)
- Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Volume of Distribution(alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose)
- Pharmacodynamic Analysis: Pharmacodynamics Quantitation of natural killer (NK) cells in peripheral blood(From screening through Day 84)
- Pharmacodynamic Analysis: Pharmacodynamics Quantitation of total lymphocytes in peripheral blood(From screening through Day 84)
- Investigators assessed overall response rate according to the European Leukemia Net (ELN) Response Criteria(At Day 28, Day 56, Day 84, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21 and Month 24)
- Duration of Response(From the date of the initial response to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24)
- Overall Survival(From the first day of study treatment to the date of death from any cause, assessed up to Month 24)
- Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain time to reach Cmax (Tmax)(alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose)
- Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain total area under curve from zero to infinity (AUC-infinity)(alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose)
- Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Terminal Rate(alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose)
- Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Terminal Half-life(alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose)
- Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Clearance(alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose)
- Pharmacodynamic Analysis: Pharmacodynamics Quantitation of T cells in peripheral blood(From screening through Day 84)
- Pharmacodynamic Analysis: Pharmacodynamics Quantitation of B cells in peripheral blood(From screening through Day 84)
- Pharmacodynamic Analysis: Pharmacodynamics Monitoring of the incidence of anti-cluster of differentiation 52 (anti-CD52; alemtuzumab) antibodies (ADA) in serum Pre-alemtuzumab administration and through Day 84(From screening through Day 84)
研究者
研究点 (8)
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