A Phase 1 Safety and Efficacy Study of ADI-001 Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T Cells in Adults With B Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 34
- 试验地点
- 10
- 主要终点
- Proportion of treatment emergent and treatment related adverse events
研究概览
简要总结
This is a Phase 1 dose escalation study following a 3+3 study design. The purpose of this study is to evaluate the safety and efficacy of ADI-001 in patients with B cell malignancies.
详细描述
ADI-001 is an investigational immunotherapy composed of allogeneic gamma delta T cells that is being evaluated as a potential treatment for patients diagnosed with B cell malignancies who have relapsed or are refractory to at least two prior regimens. This first-in-human study will assess the safety and tolerability of ADI-001 and is designed to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). Patients will be administered a single infusion or multiple infusions of ADI-001 cells. The study will include the following two parts:
Part 1 : dose escalation and extension. Parts 1a (escalation) and 1b (extension) will involve escalation and administration of single dose of ADI-001 and multiple doses of ADI-001.
Part 2 : dose expansion will involve dose administration of ADI-001 at MTD/MAD as determined in Part 1.
The study will also assess the pharmacokinetics and pharmacodynamics of ADI-001.
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
- •Relapsed/refractory (R/R) previously treated B cell malignancies.
- •Prior treatment must include at least 2 prior regimens, including anti CD20 antibody therapies. Prior Treatment with CD19 CAR T may be considered.
- •Documented measurable disease as defined by Lugano 2014
- •Male or female ≥ 18 years of age
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- •Adequate hematological, renal, pulmonary, cardiac, and liver function
- •Female patients who are not pregnant or breastfeeding
- •Female patients of childbearing potential and all male patients must agree to use highly effective methods of birth control for the duration of the study.
排除标准
- •Current or history of any of the following conditions:
- •Central nervous system (CNS) primary lymphoma (current or history)
- •Unrelated malignancy requiring systemic treatment (current or history [in the past 3 years, other than hormonal treatment which is allowed])
- •Any of the following current conditions:
- •Active acute or chronic graft versus host disease (GvHD) other than grade 1 with skin involvement, or GvHD requiring immunosuppressive treatment within 4 weeks of enrollment
- •Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration
- •Tumor mass effects such as bowel obstruction or blood vessel compression that require therapy
- •Opportunistic infections
- •History of any clinically significant conditions in the opinion of the Investigator
- •Prior treatment with any of the following:
- •a Gene therapy, genetically modified cell therapy, or adoptive T cell therapy within 6 weeks of study enrollment.
- •b Radiation therapy within 4 weeks prior to study entry. Palliative local radiation may be allowed within 1 week prior to study entry.
- •c Autologous stem cell transplant (SCT) within 6 weeks of planned ADI 001 infusion.
- •d Allogeneic transplant and donor lymphocyte infusion within 3 months of planned CAR T cell infusion
- •Patients unwilling to participate in an extended safety monitoring period (long term follow up [LTFU] protocol)
研究组 & 干预措施
ADI-001 Dose Escalation
ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).
干预措施: ADI-001 (Genetic)
ADI-001 Dose Escalation
ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).
干预措施: Fludarabine (Drug)
ADI-001 Dose Escalation
ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).
干预措施: Cyclophosphamide (Drug)
ADI-001 Dose Extension
ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
干预措施: ADI-001 (Genetic)
ADI-001 Dose Extension
ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
干预措施: Fludarabine (Drug)
ADI-001 Dose Extension
ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
干预措施: Cyclophosphamide (Drug)
ADI-001 Dose Expansion
Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
干预措施: ADI-001 (Genetic)
ADI-001 Dose Expansion
Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
干预措施: Fludarabine (Drug)
ADI-001 Dose Expansion
Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Proportion of treatment emergent and treatment related adverse events
时间窗: 1 year
This primary endpoint will be used to determine the MTD/MAD of ADI-001
The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort
时间窗: Day 28
This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD).
次要结局
- Progression Free Survival(Day 28, Month 3, 6, 9, and 12)
- Time To Progression(Day 28, Month 3, 6, 9, and 12)
- Overall Survival(Day 28, Month 3, 6, 9, and 12)
- Frequency and persistence of ADI-001(Day 1 through Month 12)
- Duration of Response(Day 28, Month 3, 6, 9, and 12)
- Overall Response Rate by Lugano Criteria(Day 28, Month 3, 6, 9, and 12)