A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LUCAR-20SP, an Allogenic Chimeric Antigen Receptor(CAR)-T Cell Therapy Targeting CD20 in Subjects with Relapsed/refractory B-cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- Pharmacokinetics in bone marrow
研究概览
简要总结
This is a prospective, single-arm, open-label, exploratory clinical study of LUCAR-20SP in adult subjects with relapsed/refractory B-cell non-Hodgkin lymphoma.
详细描述
This is a prospective, single-arm, open-label exploratory clinical study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor efficacy profiles of LUCAR-20SP, an allogenic CAR-T cell therapy in subjects with relapsed/refractory B-cell non-Hodgkin lymphoma. Patients who meet the eligibility criteria will receive LUCAR-20SP infusion. The study will include the following sequential stages: screening, pre-treatment (lymphodepleting chemotherapy), treatment and follow-up.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects voluntarily participate in clinical research;
- •Age ≥18 years old;
- •Eastern Cooperative Oncology Group (ECOG) score 0-1;
- •Histologically confirmed large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, histologically indolent lymphoma to diffuse large B-cell lymphoma; CD20 positive;
- •At least one measurable tumor lesion according to the Lugano
- •Expected survival ≥3 months;
- •Clinical laboratory values in the screening period meet criteria.
- •Effective contraception.
排除标准
- •Prior antitumor therapy with insufficient washout period.
- •Previous treatment with allogeneic cell and gene therapy (such as CAR-T); Except subjects with evidence that previous allogeneic cell and gene therapy products (such as CAR-positive T cells and CAR transgenes) in the subject have been below the lower limit of detection;
- •Previously received allogeneic hematopoietic stem cell transplantation;
- •Previously received gene therapy;
- •Donor specific antibody (DSA) positive subjects will be excluded;
- •Severe underlying diseases;
- •Hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C virus ribonucleic acid (HCV RNA) or human immunodeficiency virus antibody (HIV-Ab) positive;
- •Presence of other serious pre-existing medical conditions that may limit patient participation in the study. Any condition that, in the investigator's judgment, will make the subject unsuitable for participation in this study.
研究组 & 干预措施
Each subject will receive LUCAR-20SP cells
Chimeric antigen receptor T cells LUCAR-20SP cells
干预措施: LUCAR-20SP cells (Biological)
结局指标
主要结局
Pharmacokinetics in bone marrow
时间窗: Minimum 2 years after LUCAR-20SP infusion (Day 1)
CAR positive T cells levels in bone marrow after LUCAR-20SP infusion. CAR transgene levels in bone marrow after LUCAR-20SP infusion.
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
时间窗: Minimum 2 years after LUCAR-20SP infusion (Day 1)
An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment.
Recommended Phase 2 Dose (RP2D) regimen finding
时间窗: Minimum 2 years after LUCAR-20SP infusion (Day 1)
RP2D established through accelerated titration design (ATD) and Bayesian Optimal Interval (BOIN) design.
Pharmacokinetics in peripheral blood
时间窗: Minimum 2 years after LUCAR-20SP infusion (Day 1)
CAR transgene levels in peripheral blood after LUCAR-20SP infusion. CAR positive T cells levels in bone marrow after LUCAR-20SP infusion.
Dose-limiting toxicity (DLT) rate
时间窗: Minimum 2 years after LUCAR-20SP infusion (Day 1)
DLT refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose.
次要结局
- Objective Response Rate (ORR) after administration(Minimum 2 years after LUCAR-20SP infusion (Day 1))
- Duration of Remission (DoR) after administration(Minimum 2 years after LUCAR-20SP infusion (Day 1))
- Overall Survival (OS) after administration(Minimum 2 years after LUCAR-20SP infusion (Day 1)])
- Progression-free Survival (PFS) after administration(Minimum 2 years after LUCAR-20SP infusion (Day 1)])
- Incidence of anti-LUCAR-20SP antibody(Minimum 2 years after LUCAR-20SP infusion (Day 1))
- Time to Response (TTR) after administration(Minimum 2 years after LUCAR-20SP infusion (Day 1))