Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection
详细描述
Epstein-Barr virus (EBV) is a widely disseminated herpesvirus that is spread by intimate contact between susceptible persons and asymptomatic EBV shedders. The inability to control EBV infection can lead to some patients developing EBV-positive B-cell lymphomas, chronic active EBV infections, and hemophagocytic lymphohistiocytosis (HLH). In this prospective study, HLA-A*02:01/11:01/24:02-restricted EBV-specific T cell receptor (TCR) will be introduced into the T cells of donors by ex vivo lentiviral transduction to generate EBV-TCR-T cells. An escalated dose ranging from 1×10^6/kg to 1×10^8/kg of EBV-TCR-T cells will be infused into patients with EBV-HLH or EBV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic EBV-TCR-T cell therapy will be evaluated.
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
- 1 Year 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 1-60 years, gender unlimited.
- •Diagnosed with EBV associated-hemophagocytic lymphohistiocytosis (HLH) or EBV infection.
- •Fully understood and informed the study and signed the ICF.
- •Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
- •TCRT-T cell donor inclusion criteria: 1)Age >=8 years, gender unlimited; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8~4) × 10^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.
排除标准
- •Patients with uncontrolled active aGVHD one day before TCR-T cell infusion.
- •Patients with severe kidney disease (Cr > 3×normal value), liver damage (TBIL >2.5×upper limit of normal value, ALT and AST > 3×upper limit of normal value) or heart failure (NYHA heart function grade IV or left ventricular ejection fraction<50%) one week before TCR-T cell infusion.
- •Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
- •Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
- •Have tumours, active and uncontrolled malignant diseases.
- •Serologically positive for HIV-Ab or TAP-ab.
- •Pregnant or lactating women.
- •Men and their partners or women of childbearing potential refused contraception during the study period.
- •Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
- •Participated in any other clinical study of drugs and medical devices before 4 weeks of enrollment.
- •Allergy to albumin.
- •TCRT-T cell donor exclusion criteria: 1) pregnant woman; 2) Serologically positive for HBsAg, HCV-Ab, HIV-Ab or TAP-ab; 3) EBV-DNA or CMV-DNA positive; 4) other uncontrolled infection; 5) Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
结局指标
主要结局
Adverse events
时间窗: 1 year after EBV-TCR-T treatment
Percentage of participants with adverse events
次要结局
- The proportion of EBV-DNA negative patients(180 days after EBV-TCR-T treatment)
- Dose-limiting toxicity (DLT)(28 days after EBV-TCR-T treatment)
- Maximum tolerated dose （MTD）(28 days after EBV-TCR-T treatment)
- The time to EBV-DNA negative(180 days after EBV-TCR-T treatment)
- Changes of EBV-DNA copies number(1 year after EBV-TCR-T treatment)
- Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells(28 days after EBV-TCR-T treatment)
- Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells(28 days after EBV-TCR-T treatment)
- Time to peak (Tmax) of EBV-TCR-T cells(28 days after EBV-TCR-T treatment)
- Half life time (T1/2) of EBV-TCR-T cells(28 days after EBV-TCR-T treatment)
研究者
Daihong Liu
Director
Chinese PLA General Hospital