A Phase I, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LUCAR-E9D,LUCAR-E9K, a Dual-targeted Cell Product 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
- 发起方
- 入组人数
- 48
- 试验地点
- 3
- 主要终点
- Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events)
研究概览
简要总结
A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LUCAR-E9D,LUCAR-E9K, 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-E9D,LUCAR-E9K 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-E9D,LUCAR-E9K 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:
- •1） Patients with B-NHL who are primary refractory and are unsuitable or unwilling to receive autologous CAR-T cell therapy; 2） primary refractory is defined as the best response to first-line treatment being SD or PD; 3） Relapse within 12 months after achieving CR with first-line chemotherapy and immunotherapy;
- •Life expectancy≥ 3 months
- •Women of childbearing potential must have a negative highly sensitive serum pregnancy test (β-human chorionic gonadotropin [β-hCG]) at screening and before the first administration of cyclophosphamide and fludarabine treatment;
排除标准
- •Diagnosed with or treated for other invasive malignancies besides B-cell non-Hodgkin lymphoma.
- •Active acute or chronic graft-versus-host disease (GVHD), except for grade 1 skin involvement; or requiring immunosuppressive treatment for GVHD within 4 weeks prior to enrollment;
- •Active CNS involvement (symptomatic or positive cerebrospinal fluid or imaging data), prior CNS infiltration but currently in remission (asymptomatic and negative cerebrospinal fluid and/or imaging data) is eligible;
- •Significant bleeding tendency, such as gastrointestinal bleeding, hemorrhagic cystitis, coagulopathy.
- •Chronic diseases treated with steroids or other immunosuppressants. The following situations are excluded: use of topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids for prophylaxis;
- •Severe underlying diseases, such as: - Evidence of severe active viral, bacterial infections, or uncontrolled systemic fungal infections; - Active or unstable autoimmune diseases, or autoimmune diseases within the past 3 years with potential for relapse;
- •Breastfeeding women;
研究组 & 干预措施
LUCAR-E9D or LUCAR-E9K
Each subject will be given a single-dose LUCAR-E9D or LUCAR-E9K cells infusion at each dose level.
干预措施: LUCAR-E9D or LUCAR-E9K cells product (Biological)
结局指标
主要结局
Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events)
时间窗: 2 years after LUCAR-E9D,LUCAR-E9K infusion
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: 2 years after LUCAR-E9D,LUCAR-E9K infusion
CAR positive T cells and CAR transgene levels in peripheral blood after LUCAR-E9D,LUCAR-E9K infusion.
Pharmacokinetics in bone marrow
时间窗: 2 years after LUCAR-E9D,LUCAR-E9K infusion
CAR positive T cells and CAR transgene levels in bone marrow after LUCAR-E9D,LUCAR-E9K infusion.
The recommended Phase II dose (RP2D) for this cell therapy
时间窗: 30 days after LUCAR-E9D,LUCAR-E9K infusion
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
次要结局
- Overall Survival (OS)(Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion)
- Overall Response Rate (ORR)(Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion)
- Progression-free survival (PFS)(Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion)
- Time to Response (TTR)(Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion)
- Duration of Response (DoR)(Through study completion, minimum 2 years after LUCAR-E9D,LUCAR-E9K infusion (Day 1))
- Immunogenicity assessment of LUCAR-E9D or LUCAR-E9Kcells(Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion)