A Multi-center, Single Arm, Open-label Phase 1/2 Clinical Trial to Evaluate Safety, and to Explore Efficacy of TC011(CD19 Targeted CAR-T) in the Relapsed/Refractory Large B Cell Non-Hodgkin Lymphoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Phase1: Occurrence of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a multi-center, phase I/II study to determine the safety and efficacy of TC011(CD19 Targeted CAR-T) in adult patients with relapsed or refractory large B-cell non -hodgkin lymphoma.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all criteria including:
- •≥19 years old, ECOG 0-2, life expectancy ≥12 weeks
- •Histologically confirmed B-cell lymphoma (WHO 2017)
- •Relapsed/refractory after ≥2 prior lines of systemic chemotherapy
- •≥1 measurable lesion (longest diameter ≥1.5 cm)
- •Adequate organ, and pulmonary function
- •LVEF ≥40%
- •Able to undergo leukapheresis
- •For subjects of childbearing potential: agreement to use effective contraception for ≥6 months after TC011 infusion
排除标准
- •Unresolved ≥Grade 2 toxicities from prior therapy
- •Malignancy within 2 years except specified exceptions
- •Significant cardiac disease within 6 months
- •CNS involvement by lymphoma
- •Active HBV, HCV, HIV, syphilis
- •Rapidly progressing disease per investigator
- •Major surgery requiring general anesthesia within 4 weeks
- •Active or uncontrolled infection
- •Prior therapies such as anti-CD19 agents, adoptive T-cell therapy, gene therapy, allogeneic HSCT
- •Use of other investigational agents, immunosuppressants within protocol-specified windows
- •Pregnancy or breastfeeding
- •Hypersensitivity to study drug components
- •Leukapheresis-specific exclusions (recent chemotherapy, steroids, immunosuppressants)
研究组 & 干预措施
TC011
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, TC011.
干预措施: TC011 (Drug)
结局指标
主要结局
Phase1: Occurrence of Dose-Limiting Toxicities (DLTs)
时间窗: Up to 4 weeks after TC011 infusion
A dose-limiting toxicity (DLT) is defined as any toxicity that is definitely related or probably related to the administration of TC011. The severity of toxicities will be assessed according to CTCAE Version 5.0, while cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be evaluated based on the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading .
Phase1: Determination of Maximum Tolerated Dose (MTD)
时间窗: up to 4weeks after TC011 infusion
DLT occurrence within the first 4 weeks after treatment initiation will be used to determine the maximum tolerated dose (MTD) .
Phase1: Determination of Recommended Phase 2 Dose (RP2D)
时间窗: Up to 12 weeks after TC011 infusion
The recommended Phase 2 dose (RP2D) will be determined based on evaluation of safety (including DLT incidence), tolerability, overall adverse event profile, and preliminary anti-tumor activity observed during the dose-escalation phase.
Phase 1: The number and incidence rate of treatment-emergent adverse events (TEAEs) as well as serious adverse events (SAEs) will be assessed
时间窗: Up to 12 weeks after TC011 infusion
All adverse events (AEs) will be graded according to CTCAE version 5.0. Adverse events of special interest include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria.
Phase1: Number of participants with abnormal physical examination findings
时间窗: Baseline through Week 12
Clinically significant abnormalities identified during comprehensive physical examinations (general appearance, cardiovascular, respiratory, abdominal, neurologic, lymphatic systems) will be recorded.
Phase1: Number of participants with abnormal vital signs
时间窗: Baseline through Week 12
Abnormal vital signs (systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and body temperature) will be documented according to clinical significance.
Phase1: Number of participants with abnormal ECG readings
时间窗: Baseline through Week 12
ECG findings will be categorized as Normal, Abnormal - Not Clinically Significant, or Abnormal - Clinically Significant.
Phase 1 : Number of participants with abnormal laboratory test results
时间窗: Baseline through Week 12
Abnormal results from hematology, chemistry, liver function tests, renal function tests, coagulation, and other relevant laboratory parameters will be recorded.
Phase 1 : Presence of Replication-Competent Lentivirus (RCL) Through Week 12
时间窗: Baseline through Week 12
Peripheral blood samples will be collected to evaluate the presence of replication-competent lentivirus (RCL). Samples will be analyzed by the central laboratory (BioComplete). If RCL is detected by quantitative PCR, additional confirmatory analyses and patient follow-up- including assessment of medical history for lentivirus-associated diseases such as malignancies, neurological disorders, or serologic conditions-will be conducted.
Phase 2 : Objective Response Rate (ORR)
时间窗: up to 24 weeks after TC011 infusion
as the proportion of subjects achieving complete response (CR) or partial response (PR) as their best overall response (BOR) per the Lugano Criteria for Response Assessment (2014).
次要结局
- Phase 1: Overall response rate (ORR)(4weeks and 12weeks after TC011 infusion)
- Phase 2: Objective response rate (ORR)(Weeks 4, 12, 24, 48, 72, and 96)
- Phase 2 Disease control rate (DCR)(at Weeks 4, 12, 24, 48, 72, and 96)
- Phase 2: Complete response rate (CRR)(at Weeks 4, 12, 24, 48, 72, and 96)
- Phase 2: Partial response rate (PRR)(at Weeks 4, 12, 24, 48, 72, and 96)
- Phase 2: Stable disease rate (SDR)(at Weeks 4, 12, 24, 48, 72, and 96)
- Phase 2: Progression-free survival (PFS)(at Weeks 4, 12, 24, 48, 72, and 96)
- Phase 2: Overall survival (OS)(at Weeks 4, 12, 24, 48, 72, and 96)
- Phase 2: Time to response (TTR)(at Weeks 4, 12, 24, 48, 72, and 96)