Cytomegalovirus Specific Cytotoxic T Lymphocyte for the Treatment of Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- 30-day response rate
研究概览
简要总结
Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality for recipients of allogeneic hematopoietic stem cell transplantation(HSCT). we propose to study the immunologic and virologic effects of donor derived CMV specific cytotoxic T lymphocyte (CMV-CTL) given to transplant recipients
CMV antigen peptides will be used to induce the CMV antigen specific T lymphocytes derived from donor peripheral blood mononuclear cells for a period of 18~21 days.The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA level will be monitored weekly after transfusion.
详细描述
Allogeneic hematopoietic stem cell transplantation is widely used for the treatment of hematological malignancies and bone marrow failure diseases. Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality for recipients of allogeneic hematopoietic stem cell transplantation(HSCT). Approximately half of the recipients would develop CMV infection after transplant. Present treatment recommendation for CMV infection including ganciclovir and foscarnet. However, these medications have many side effects, the most serious is myelosuppression and renal injury, moreover, many patients do not response to these medications. Considering the risk associated with persistent infection and the potential for CMV specific cytotoxic T lymphocyte (CMV-CTL) to restore immunity, we propose to study the immunologic and virologic effects of donor derived CMV-CTL given to transplant recipients, levels of CMV-CTL and CMV DNA will be measured from CTL recipients.
If the patient and their donor are eligible, we will take 80 ml of fresh blood from the donor or 5 ml peripheral blood stem cell from the donor.The peripheral blood mononuclear cells will be separated from peripheral blood or peripheral blood stem cell. CMV antigen peptides will be used to induce the CMV-CTL for a period of 18~21 days.
The donor derived CMV-CTL cells will be transfused into the patients' intravenous line. The patients will receive the dose of CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir, Foscarnet.
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
- 14 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any allogeneic stem cell transplant recipient ≥ 14 years of age and ≤ 60 years of age
- •Bilirubin/ SGOT/SGPT < 5 × upper normal limits.
- •Creatinine < 2 × upper normal limits.
- •Ejection fraction ≥ 50%, no severe arrhythmia.
- •Estimated life expectancy ≥ 6 months.
- •Patients' CMV-DNA ≥ 1000cp/ml in treatment group and being negative in prophylactic group.
排除标准
- •Patients receiving prednisone ≥ 1mg/kg/d for the treatment of acute GVHD or mild, severe chronic GVHD.
- •Recipient < 14years of age
- •Donor is sero-positive in HBV/HCV/HIV or RPR.
研究组 & 干预措施
CMV-CTL
The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CMV-CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir or Foscarnet.
干预措施: Foscarnet (Drug)
CMV-CTL
The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CMV-CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir or Foscarnet.
干预措施: donor derived cytomegalovirus specific T lymphocytes (Biological)
CMV-CTL
The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CMV-CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir or Foscarnet.
干预措施: Ganciclovir (Drug)
结局指标
主要结局
30-day response rate
时间窗: from the date of CMV-CTL infusion to 30 days after the infusion
The percentage of patient whose serum CMV-DNA becomes negative in 30 days.
次要结局
- 100-day incidence of acute GVHD(from the date of transplant to 100 days after transplant)
- 1-year incidence of chronic GVHD(from the date of transplant to 1 year after transplant)
- 1-year overall survival(from the date of transplant to 1 year after transplant)
研究者
Liping Wan
Chief Physician
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine