Adoptive Immunotherapy With Donor-derived CMV-TCR-T Cells for Patients With CMV Infection After Allogenic HSCT
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 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 CMV-TCR-T cell immunotherapy in treating CMV virus infection after allogenic HSCT.
详细描述
Cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT) is common and can be lethal without prompt treatment. In this prospective study, HLA-A*02:01/11:01/24:02-restricted CMV-specific T cell receptor (TCR) will be introduced into the T cells of HSCT donors by ex vivo lentiviral transduction to generate CMV-TCR-T cells. An escalated dose ranging from 1×10^3/kg to 5×10^5/kg of CMV-TCR-T cells will be infused into patients with CMV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic CMV-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 hematologic malignancies and have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), with CMV infection after allo-HSCT.
- •Karnofsky Score ≥ 70 or Lansky Score ≥
- •TCR-T cell donor inclusion criteria:
- •Age ≥ 8 years; 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 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) one week before TCR-T cell infusion.
- •Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
- •Have other malignancies.
- •Have relapsed and uncontrolled hematologic malignancies.
- •Serologically positive for HIV-Ab or TAP-ab.
- •Pregnant or lactating women.
- •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 30 days of enrollment.
- •Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
- •TCR-T cell donor exclusion criteria:
- •Positive for any of the following: HbsAg, HBeAg, HBV-DNA, HCV-Ab, HCV-RNA, HIV-Ab, TP-Ab, EBV-DNA or CMV-DNA;
- •Other uncontrolled infection;
- •Have taken immunosuppressive drugs 1 week before PBMC collection;
- •Any condition that would, in the investigator's judgment, make it unsuitable for the donors to be enrolled.
结局指标
主要结局
Adverse events
时间窗: 1 year
Percentage of participants with adverse events.
次要结局
- Persistence of CMV-TCR-T cells(1 year)
- Changes of CMV-DNA copies number(1 year)
研究者
Daihong Liu
Director
Chinese PLA General Hospital