Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Genethon
- 入组人数
- 6
- 试验地点
- 4
- 主要终点
- Reduction in the frequency and severity of bruising and bleeding episodes
研究概览
简要总结
This is a phase I/II study to evaluate the safety and efficacy of Hematopoietic Stem Cell genetherapy for the Wiskott-Aldrich Syndrome.
详细描述
This clinical trial is an ex vivo gene therapy trial. The investigational product corresponds to autologous CD34+ cells transduced with a lentiviral vector harboring the human WASP gene.
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
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •males of all ages
- •severe WAS (clinical score 3-5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry
- •molecular confirmation by WAS gene DNA sequencing
- •lack of HLA-genotypically identical bone marrow or of a 10/10 antigen HLA-matched unrelated donor or cord blood after 3 month search
- •parental, guardian, patient signed informed consent/assent
- •willing to return for follow-up
- •only for patients who have received previous allogenic hematopoietic stem cell transplant:
- •failed allogenic hematopoietic stem cell transplant
- •contraindication to repeat transplantation
排除标准
- •patient with HLA-genotypically identical bone marrow
- •patient with 10/10 antigen HLA-matched unrelated donor or cord blood
- •contraindication to leukapheresis
- •contraindication to bone marrow harvest
- •contraindication to administration of conditioning medication
- •HIV positive patient
结局指标
主要结局
Reduction in the frequency and severity of bruising and bleeding episodes
时间窗: 2 years
Reduction in the frequency and severity of bruising and bleeding episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry
Improvement in the eczema status
时间窗: 2 years
Improvement in the eczema status as compared with the baseline status at study entry on clinical evaluation
Reduction in the number of disease related days of hospitalization
时间窗: 2 years
Reduction in the number of disease related days of hospitalization as compared with the patient's historical data collected over the 2 years prior to study entry
Reduction in the frequency and severity of infection episodes
时间窗: 2 years
Reduction in the frequency and severity of infection episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry
Reduction in the frequency and severity of autoimmune disorders
时间窗: 2 years
Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry
次要结局
- Change in medical conditions(2 years)
- Improvement of microthrombocytopenia(3, 6, 12, 24 months)
- Evidence of sustained engrafment of WASP-expressing transduced cells(6 weeks, 1, 3, 6, 9, 12, 18 & 24 months)
- Occurrence and type of adverse events(2 years)
- Reconstitution of humoral and cell mediated immunity(9, 12, 18 & 24 months)
- Safety of lentivirus gene transfer into Hematopoietic Stem Cells(3, 6, 12, 24 months / 6, 12, 18, 24 months)
- Decrease in the number and volume of platelets transfusions(2 years)