A Phase I, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LCAR-AIO, a Triple-targeted Cell Preparation Targeting CD19/CD20/CD22, in Patients With Relapsed/Refractory B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Pharmacokinetics in bone marrow
研究概览
简要总结
A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LCAR-AIO, a triple-targeted cell preparation targeting CD19/CD20/CD22, in patients with relapsed/refractory B-cell lymphoma.
详细描述
This is an open-label, dose-escalation/dose extension study to assess the safety, tolerability, and efficacy of LCAR-AIO in the patient ≥ 18 years of age with relapsed or refractory B cell lymphoma. Subjects who meet the eligibility criteria will receive a single dose of LCAR-AIO injection. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; 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 lymphoma that expresses at least one of CD19/CD20/CD
- •At least one measurable tumor lesion determined according to Lugano 2014 criteria.
- •Response to prior therapy is consistent with one of the following:
- •Primary refractory: it means that the best response to first-line therapy (at least 2 cycles) is PD, or best response to first-line therapy (at least 4 cycles) is SD but the duration is less than 6 months, which is considered to be PD;
- •Relapsed or refractory after 2 or more lines of therapy. Refractory is defined that best respond to the most recent treatment regimen (at least 2 cycles) is PD, or best response to the most recent treatment regimen (at least 4 cycles) is SD but the duration is less than 6 months, which is considered to be PD;
- •Progression or relapse within 12 months after hematopoietic stem cell transplantation; if salvage therapy is applied after transplantation, the patient must be unresponsive or relapsed to the last line of therapy;
- •Life expectancy≥ 3 months
- •Clinical laboratory values meet screening visit criteria
- •Adequate organ function;
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 dual-targeted CAR-T cell therapy (including but not limited to sequential infusion) at any time in the past, or who received CAR-T cell therapy of cameloid origin;
- •With acute or chronic graft-versus-host disease (GvHD);
- •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 LCAR-AIO CAR-T cell or its excipients, including DMSO (refer to Investigator's Brochure).
- •Pregnant or lactating women;
研究组 & 干预措施
LCAR-AIO cells product
Each subject will be given a single-dose LCAR-AIO cells infusion at each dose level.
干预措施: LCAR-AIO cells product (Biological)
结局指标
主要结局
Pharmacokinetics in bone marrow
时间窗: Minimum 2 years after LCAR-AIO infusion (Day 1)
CAR positive T cells and CAR transgene levels in bone marrow after LCAR-AIO infusion.
The recommended Phase II dose (RP2D) for this cell therapy
时间窗: 30 days after LCAR-AIO infusion
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events)
时间窗: Minimum 2 years after LCAR-AIO 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.
Pharmacokinetics in peripheral blood
时间窗: Minimum 2 years after LCAR-AIO infusion (Day 1)
CAR positive T cells and CAR transgene levels in peripheral blood after LCAR-AIO infusion.
次要结局
- Time to Response (TTR)(Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1))
- Overall Survival (OS)(Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1))
- Duration of Response (DoR)(Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1))
- Overall Response Rate (ORR)(Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1))
- Progression-free survival (PFS)(Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1))
- Immunogenicity assessment of LCAR-AIO cells(Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1))