A Prospective Exploratory Study of EBV-AST Cell Injection for the Treatment of EBV-Related Diseases After Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of EBV-AST Cell Infusion
研究概览
简要总结
This exploratory clinical study focuses on the use of EBV-AST cell infusion for treating EBV-DNA viremia following allogeneic hematopoietic stem cell transplantation (Allo-HSCT). The study aims to determine the maximum tolerated dose (MTD) or optimal biological dose (OBD) of EBV-AST cells and assess their safety, tolerability, and preliminary efficacy in treating EBV-DNA viremia. The study will involve a 3+3 dose escalation design to evaluate three different dosages of EBV-AST cell infusion. The study is expected to provide important insights into the clinical application of cell-based therapies for EBV infections.
详细描述
This clinical trial, initiated by the First Medical Center of the Chinese People's Liberation Army General Hospital, will recruit patients who have experienced EBV-DNA viremia following Allo-HSCT. Patients eligible for inclusion must exhibit EBV-DNA viremia that requires clinical intervention and should meet the inclusion criteria set for the study.
The research employs a 3+3 dose escalation methodology where three dosage groups are evaluated: 5×10^5 cells/Kg, 1×10^6 cells/Kg, and 5×10^6 cells/Kg. Each patient will receive up to three infusions, one per week. The study will monitor both the safety and the preliminary efficacy of the infusions, including their ability to reduce EBV-DNA levels and the duration of EBV-DNA negativity. The trial will also assess the pharmacokinetics (PK) and pharmacodynamics (PD) of the EBV-AST cell infusion.
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
- •The patient must be aged 18-75 years.
- •ust have undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT).
- •Must have EBV-DNA viremia post-transplant, with EBV-DNA > 1000 copies/mL (on two consecutive tests or one test > 10,000 copies/mL).
- •Karnofsky Performance Score (KPS) of 70 or higher.
- •Expected survival of at least 3 months.
- •Sufficient organ function, including renal (serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min), hepatic (AST, ALT, and total bilirubin ≤ 5 × ULN), and hematologic parameters (platelets ≥ 10 × 10^9/L, neutrophils ≥ 1.0 × 10^9/L).
- •HLA-matching criteria must be met for the donor/recipient.
排除标准
- •Active GVHD (Grade 2 or higher) or requiring >0.5 mg/kg/day corticosteroids for GVHD.
- •History of CMV viremia or disease within the past week.
- •PTLD (Post-Transplant Lymphoproliferative Disorder) diagnosed or suspected within 1 week before infusion.
- •Severe active infections (excluding EBV and CMV).
- •Serious allergic reactions or contraindications to the infusion.
- •Previous immune therapy-related adverse events of Grade 3 or higher.
- •History of HIV, HCV, or HBV infection with an active viral load.
研究组 & 干预措施
EBV-AST cell infusion
EBV-AST (EBV-specific cell infusion) for the treatment of EBV-DNA viremia in patients post-Allo-HSCT.
干预措施: EBV-AST cell (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of EBV-AST Cell Infusion
时间窗: Day 1 through 28 days after each EBV-AST cell infusion during the dose escalation phase.
The primary outcome measure of the study is to determine the maximum tolerated dose (MTD) of EBV-AST cell infusion in patients with EBV-DNA viremia following allogeneic hematopoietic stem cell transplantation (Allo-HSCT). A dose-escalation design (5×10\^5, 1×10\^6, and 5×10\^6 cells/kg) will be used to evaluate safety and tolerability based on the occurrence of dose-limiting toxicities (DLTs).
次要结局
- Proportion of Patients Achieving EBV-DNA Negativity(8 weeks and 12 weeks after EBV-AST cell infusion.)
- Change in EBV-DNA Levels(Baseline through 12 weeks after EBV-AST cell infusion.)
- Time to EBV-DNA Negativity(Up to 12 weeks after EBV-AST cell infusion.)
- Absolute Concentration of Circulating EBV-AST Cells in Peripheral Blood at Pre-specified Time Points(Baseline through 28 days after EBV-AST cell infusion)
- Change in EBV-Specific T-Cell Frequency in Peripheral Blood(Baseline through 12 weeks after EBV-AST cell infusion.)
研究者
Daihong Liu
Director, Department of Hematology
Chinese PLA General Hospital