A Phase I, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LUCAR-G39D, a Dual-targeted Cell Preparation Targeting CD19/CD20, in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Pharmacokinetics in peripheral blood
研究概览
简要总结
A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LUCAR-G39D, a dual-targeted cell preparation targeting CD19/CD20, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.
详细描述
This is an open-label, dose-escalation/dose extension study to assess the safety, tolerability, and efficacy of LUCAR-G39D in the patient ≥ 18 years of age with relapsed or refractory B-cell non-Hodgkin lymphoma. Subjects who meet the eligibility criteria will receive a single dose of LUCAR-G39D injection. The study will include the following sequential phases: 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent.
- •Aged 18-75 years (inclusive).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Histologically confirmed B-cell non-Hodgkin Lymphoma that expresses at least one of CD19/CD
- •At least one evaluable tumor lesion according to Lugano 2014 criteria.
- •Response to prior therapy is consistent with one of the following:
- •Primary refractory.
- •Relapsed or refractory after 2 or more lines of therapy.
- •For LBCL, 3B FL. t-iNHL:
- •Relapse within 12 months after first-line chemoimmunotherapy to achieve CR;
- •Progression or relapse within 12 months after autologous hematopoietic stem cell transplantation;
- •Life expectancy≥ 3 months
- •Clinical laboratory values meet screening visit criteria
排除标准
- •Subject eligible for this study must not meet any of the following criteria:
- •Prior antitumor therapy with insufficient washout period ;
- •Patients who received autologous CAR-T cell therapy (except CD19-targeted) or autologous gene therapy;
- •Patients who received allogeneic hematopoietic stem cell transplantation or allogeneic therapy;
- •Patients who are positive for any index of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), or human immunodeficiency virus antibody (HIV- Ab).
- •Known life-threatening allergies, hypersensitivity, or intolerance to LUCAR-G39D CAR-T cell or its excipients, including DMSO.
- •Pregnant or lactating women;
研究组 & 干预措施
LUCAR-G39D cells product
Each subject will be given a single-dose LUCAR-G39D cells infusion at each dose level.
干预措施: LUCAR-G39D cells product (Biological)
结局指标
主要结局
Pharmacokinetics in peripheral blood
时间窗: Through study completion , an average of 2 years after LUCAR-G39D infusion (Day 1).
CAR positive T cells and CAR transgene levels in peripheral blood after LUCAR-G39D infusion.
Pharmacokinetics in bone marrow
时间窗: Through study completion , an average of 2 years after LUCAR-G39D infusion (Day 1)
CAR positive T cells and CAR transgene levels in bone marrow after LUCAR-G39D infusion.
Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events)
时间窗: Through study completion , an average of 2 years after LUCAR-G39D infusion (Day 1)
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
The recommended Phase II dose (RP2D) for this cell therapy
时间窗: Within 30 days after LUCAR-G39D infusion
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion.
次要结局
- Progression-free survival (PFS)(Through study completion, an average of 2 years after LUCAR-G39D infusion (Day 1))
- Overall Survival (OS)(Through study completion, an average of 2 years after LUCAR-G39D infusion (Day 1))
- Immunogenicity assessment of LUCAR-G39D cells(Through study completion, an average of 2 years after LUCAR-G39D infusion (Day 1))
- Overall Response Rate (ORR)(Through study completion, an average of 2 years after LUCAR-G39D infusion (Day 1))
- Time to Response (TTR)(Through study completion, an average of 2 years after LUCAR-G39D infusion (Day 1))
- Duration of Response (DoR)(Through study completion, an average of 2 years after LUCAR-G39D infusion (Day 1))
研究者
Huilai Zhang
Director of lymphoma department
Tianjin Medical University Cancer Institute and Hospital