A Prospective Clinical Study to Evaluate the Safety and Efficacy of Virus Specific T-Cell Administration in Pediatric Patients With Systemic Viral Infection Following Allogeneic Hematopoietic Stem Cell Transplantation.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Viral Load
研究概览
简要总结
The goal of this prospective clinical study is to evaluate the safety and efficacy of Multi-Virus Specific T cells (LB-DTK-MV) in pediatric patients with systemic viral infection, including CMV, EBV, and BKV, after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The main questions it aims to answer are:
- What is the maximum tolerated dose of LB-DTK-MV based on dose-limiting toxicity?
- What treatment emergent adverse events occur within 14 days after the second infusion?
- Is there a clinically significant reduction in CMV, EBV, and BKV viral loads within 14 days following the second infusion?
- Is there a clinically significant improvement in clinical symptoms within 14 days following the second infusion?
Participants will:
- Receive a single intravenous infusion of LB-DTK-MV during the baseline visit (low dose: 1x10^7/m^2; high dose: 2x10^7/m^2).
- Receive the second infusion of LB-DTK-MV intravenously at the same dose 14 days after the first infusion.
- Attend weekly follow-up visits at the clinic for 6 months after the first 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
- 1 Year 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with CMV, EBV, and/or BKV infection that is resistant or refractory to standard-of-care treatment and associated with severe complications following allogeneic hematopoietic stem cell transplantation at the ages of 1-25 years.
- •Patients with evidence of neutrophil engraftment, defined as an absolute neutrophil count (ANC) maintained at 0.5x10^3/μL or higher for 3 consecutive days following allogeneic hematopoietic stem cell transplantation.
- •Patients who have undergone allogeneic hematopoietic stem cell transplantation at least 21 days prior to the screening visit.
- •Patients who show complete donor chimerism (PCR-short tandem repeats ≥ 95%) at the time of first dose administration.
- •Patients who are able to reduce their steroid dosage to 0.5mg/kg/day of Prednisolone (or an equivalent dose) or less.
- •Individuals who have voluntarily decided to participate in this clinical study and have provided written consent to comply with the restrictions.
- •For women of childbearing potential, those who tested negative on a pregnancy test (blood test) performed on the screening visit.
- •Individuals deemed suitable as study subjects through screening tests (vital signs, physical examination, medical and surgical history, electrocardiogram, laboratory tests, etc.).
排除标准
- •Individuals who have received treatment with ATG (Antithymocyte Globulin), Campath (Alemtuzumab), or other T-cell immunosuppressive monoclonal antibodies within 28 days prior to the first dose.
- •Patients with organ failures and/or uncontrolled bacterial or fungal infections.
- •Moderate or severe liver damage [Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN)]
- •Chronic kidney disease [eGFR < 30mL/min/1.73m^2]
- •Patients who have undergone allogeneic hematopoietic stem cell transplantation or received donor lymphocyte infusion (DLI) within 28 days prior to the scheduled first dose.
- •Patients with active graft-versus-host disease (GvHD) of grade 2 or higher.
- •Patients with active malignant tumor or uncontrolled recurrence.
- •Patients deemed ineligible for participation in this clinical study by the investigator.
结局指标
主要结局
Viral Load
时间窗: From enrollment through 24 weeks after treatment initiation
CMV, EBV, and BKV viral load testing is performed using RT-PCR on blood, urine, and/or tissue samples. Viral load is measured weekly for the first 4 weeks, followed by two measurements at 2-week intervals to monitor the progression of the infection, then once every 4 weeks, and subsequently once every 12 weeks.
Immunogenicity Testing
时间窗: From enrollment through 24 weeks after treatment initiation.
Immunogenicity testing using the ELISpot assay is performed weekly for the first 4 weeks following administration of the investigational drug. Thereafter, to evaluate the persistence and reconstitution of the immune response, measurements are taken twice at 2-week intervals, once at 4-week intervals, and once at 12-week intervals. Flow cytometry will be performed concurrently at each time point to evaluate cytokine profiles and immune cell subsets.
Adverse Events
时间窗: From the baseline visit through 24 weeks after treatment initiation.
The investigator must confirm the occurrence of adverse events through medical examinations during regular visits throughout the clinical study period. Adverse events shall be assessed at each visit starting from the administration of the investigational drug at the baseline visit (Visit 2).
次要结局
未报告次要终点
研究者
JaeWon Yoo
Assistant Professor of Pediatrics
The Catholic University of Korea