Gene Transfer for Fanconi Anemia Using a Self-inactivating Lentiviral Vector
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
研究概览
简要总结
This is a Phase I/II clinical trial of gene therapy for treating Fanconi anemia using a self-inactivating lentiviral vector to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.
详细描述
Fanconi anemia is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The major problem for most patients is aplastic anemia, the blood counts for red blood cells, white blood cells, and platelets are low. In addition, some patients have physical defects usually involving the skeleton and kidneys. Fanconi anemia is typically diagnosed in childhood, and there is a high fatality rate. Hematopoietic stem cell transplantation (HSCT) is a common treatment for Fanconi anemia. However, there are many risks associated with HSCT including rejection of the transplanted cells and graft-versus-host disease.
The primary objectives are to evaluate the safety of the self-inactivating lentiviral vector, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming immune abnormalities present at the time of treatment, assessment of gene correction efficiency, and finally the long-term correction of Fanconi anemia associated disease symptoms.
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
- 2 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Fanconi anemia FANCA type based on DNA sequencing and sensitivity test for chromosomal cleavage by mitomycin C or butylene oxide.
- •No cytogenetic abnormalities and the proportion of myelodysplastic abnormalities does not exceed 5% within 3 months prior to stem cell collection.
- •Age: ≥ 4 years.
- •Karnofsky: ≥ 70%.
- •ANC ≥ 5×10^8/L; PLT ≥ 2×10^10/L.
- •Hemoglobin ≥ 8g/dL.
- •Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with
- •serum creatinine ≤ 1.5×ULN;
- •serum bilirubin ≤ 3×ULN;
- •AST/ALT ≤ 5×ULN.
- •Pulmonary function is normal; DLCO > 50%.
- •Written, informed consent obtained prior to any study-specific procedures.
排除标准
- •Diagnosis of active malignant disease or myelodysplastic syndrome.
- •Diagnosis of myeloid leukemia.
- •Pregnant or lactating females.
- •Existence of an available HLA-identical related donor.
- •Subject infected with HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.
- •Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.
研究组 & 干预措施
Gene-modified autologous stem cells
Autologous hematopoeitic stem cells and mesenchymal stem cells transduced with lentiviral vector carrying the FANCA gene ex vivo
干预措施: Gene-modified autologous stem cells (Genetic)
结局指标
主要结局
Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
时间窗: 6 months
Physiological parameter (measuring cytokine response, fever, symptoms)
次要结局
- Quality of life(1 year)
- Treatment responses(1 year)
研究者
Lung-Ji Chang
President
Shenzhen Geno-Immune Medical Institute