Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 10
- 主要终点
- Participants That Experienced Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This study will be conducted to evaluate the safety, tolerability, cellular kinetics (CK), activity, and pharmacodynamics (PD) of NTLA-5001 in participants with Acute Myeloid Leukemia (AML).
详细描述
This 2-part first in human (FIH) study is comprised of two open-label arms. It is a multi-center, Phase 1/2a study evaluating the safety and activity of NTLA-5001 in subjects with persistent or recurrent Acute Myeloid Leukemia after first-line or later therapy.
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
- •(abbreviated):
- •Has AML as defined by World Health Organization
- •Has detectable disease following first-line therapy
- •Is ≥ 18 years of age.
- •Carries the human leukocyte antigen-A0201 (HLA-A*02:01) allele.
- •Has ECOG performance status of 0 to
- •Has adequate absolute total lymphocyte count
- •Has adequate cardiac, renal, and liver organ function
排除标准
- •(abbreviated):
- •Has received AML-directed therapy or immunomodulatory therapy within a specified window prior to study entry.
- •Has received allogeneic hematopoietic cell transplant within 84 days, with ongoing GVHD, with recent DLI, or on active immunosuppression.
- •Has CNS involvement by tumor.
- •Has severe autoimmunity requiring immunomodulatory therapy.
- •Has active disseminated intravascular coagulation (DIC), bleeding or coagulopathy.
- •Has leukocytosis ≥ 20,000 blasts/μL despite hydroxyurea or has rapidly progressive disease
- •Has human immunodeficiency virus (HIV) infection, or any uncontrolled infection.
- •Female subjects are pregnant or breastfeeding; or are of childbearing potential and are unwilling to use protocol specified method of contraception.
- •Male subjects who have female partners of childbearing potential and are unwilling to use protocol specified method of contraception.
研究组 & 干预措施
Arm 1: NTLA-5001
Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count <5%, administered by IV infusion following lymphodepleting chemotherapy.
干预措施: Arm 1: NTLA-5001 (Genetic)
Arm 2: NTLA-5001
Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count ≥5%, administered by IV infusion following lymphodepleting chemotherapy.
干预措施: Arm 2: NTLA-5001 (Genetic)
结局指标
主要结局
Participants That Experienced Dose-limiting Toxicities (DLTs)
时间窗: Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion
DLTs were defined as events with onset within 28 days of infusion. AEs were collected from time of informed consent through the Week 112 visit. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0. Severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 toxicity grading criteria. The measure reported below for the primary outcome consists of DLT data only. Adverse events are reported in the Adverse Event section of this presentation.
次要结局
- Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood(From NTLA-5001 infusion up to 4 weeks post-infusion)
- Tumor Response in Participants With AML(From NTLA-5001 infusion up to 4 weeks post-infusion)
- Response Duration in Participants With AML(From NTLA-5001 infusion up to 4 weeks post-infusion)
- Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood(From NTLA-5001 infusion up to 4 weeks post-infusion)
- Disease Progression in Participants With AML(From NTLA-5001 infusion up to 4 weeks post-infusion)