A Phase I/II, Open-Label, Non-Randomized, Multicentre, Dose-Escalation Clinical Trial With Control Group to Evaluate the Safety, Feasibility and Preliminary Efficacy of PRAME TCR Modified T Cells, MDG1011, in Subjects With High Risk Myeloid and Lymphoid Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Medigene AG
- 入组人数
- 9
- 试验地点
- 9
- 主要终点
- Phase I: For feasibility: percent of all subjects who receive the planned target dose of MDG1011
研究概览
简要总结
This is a multicentre, non-randomized, open-label, Phase I/II clinical trial of MDG1011, an investigational medicinal product (IMP), consisting of patient-derived autologous T cells, persistently transduced with a Preferentially Expressed Antigen in Melanoma (PRAME)-specific human leukocyte antigen (HLA)-A*02:01-restricted T cell receptor (TCR).
详细描述
Phase I:
The Phase I dose escalation part will establish the MTD/RP2D in subjects with high risk myeloid and lymphoid neoplasms, a total of 3 disease entities.
Phase I subjects will be enrolled into the following cohorts and treated with a single intravenous (i.v.) infusion of IMP:
- Cohort 1: target dose of 1 x 105 T cells/kg ± 20%
- Cohort 2: target dose of 1 x 106 T cells/kg ± 20%
- Cohort 3: target dose of 5 x 106 T cells/kg ± 20%
- Optional cohort 4: up to 1 x 107 T cells/kg + 20%
Phase II:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
Phase I - 3 disease entities
MDG1011 administration of escalating doses
干预措施: MDG1011 (Drug)
Phase II - HLA*02:01 - disease entity 1
MDG1011 administration of Phase II recommended dose
干预措施: MDG1011 (Drug)
Phase II - HLA*other - disease entity 1
Investigator Choice therapy
干预措施: Investigator Choice therapy (Other)
Phase II - HLA*02:01 - disease entity 2
MDG1011 administration of Phase II recommended dose
干预措施: MDG1011 (Drug)
Phase II - HLA*other - disease entity 2
Investigator Choice therapy
干预措施: Investigator Choice therapy (Other)
结局指标
主要结局
Phase I: For feasibility: percent of all subjects who receive the planned target dose of MDG1011
时间窗: 3 months
Phase II: overall response rate (ORR)
时间窗: 3 months
Phase I: maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of MDG101
时间窗: 28 days
Phase II: Adverse Events (Safety)
时间窗: 3 months
Incidence and severity of adverse events according to NCI CTCAE, v4.03
Phase I: Adverse Events and Dose Limiting Toxicities (Safety and Tolerability)
时间窗: 3 months
Incidence and severity of adverse events according to the NCI CTCAE, v4.03; MTD and/or RP2D of IMP measured by dose-limiting toxicities (DLTs) up to 28 days post infusion
次要结局
- Phase I: overall response rate (ORR)(3, 6 and 12 months)
- Phase I: time to event and duration of response (DoR) rate(3, 6 and 12 months)
- Phase II: changes in quality of life (QoL)(baseline, 3, 6 and 12 months)
- Phase I: Correlation of PRAME expression with the antitumor response(3, 6 and 12 months)
- Phase II: time to event and duration of response (DoR) rate(3, 6 and 12 months)
- Phase II: time to event and time to progression (TTP) rate(3, 6 and 12 months)
- Phase II: time to event and progression-free survival (PFS) rate(3, 6 and 12 months)
- Phase II: For feasibility, the percent of all subjects who receive the RP2D of MDG1011(3 months)
- Phase II: correlation of PRAME expression with the antitumor response(3, 6 and 12 months)
- Phase I: Adverse Events (safety)(6 and 12 months)
- Phase II: Adverse Events (safety)(6 and 12 months)
- Phase I: time to event and time to progression (TTP) rate(3, 6 and 12 months)
- Phase II: time to event and overall survival (OS) rate(3, 6 and 12 months)
- Phase I: time to event and progression-free survival (PFS) rate(3, 6 and 12 months)
- Phase I: time to event and overall survival (OS) rate(3, 6 and 12 months)
- Phase I: Change in quality of life (QoL)(baseline, 3, 6 and 12 months)