Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 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 transfer for treating Beta-thalassemia using a self-inactivating lentiviral vector to functionally correct the defective gene(s). The objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.
详细描述
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
Thalassemia is considered the most common genetic disorder worldwide. Beta-thalassemia is caused by mutations in the beta-globin gene which encodes the beta-globin protein, leading to the ineffective erythropoiesis, hemolysis and anemia. Currently, the only cure for thalassemia is bone marrow transplantation from a related, compatible donor, which has, however, the significant risk of transplant related mortality, graft versus host disease and limited source. Therefore, gene therapy, achieved by transplantation of the patient's own stem cells that have been genetically-modified with the corrected gene, could potentially cure thalassemia.
This study will use a gene transfer procedure performed to insert the beta-globin gene into the participant's autologous stem cells (hematopoeitic stem cells) using a self-inactivating lentiviral vector. The purpose of this study is to evaluate the safety and effectiveness of the gene transfer procedure and to determine the ability of the gene-corrected cells at generating new, healthy blood cells in patients.
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
- 4 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Beta Thalathemia.
- •Age: ≥ 4 years.
- •Karnofsky: ≥ 80%.
- •Left ventricular ejection fraction (LVEF): > 50%; no obvious heart disease and pulmonary hypertension.
- •Pulmonary function is normal; forced expiratory volumein one second (FEV1) and vital capacity greater than 60% and DLCO > 50%.
- •Serum creatinine ≤ 2 × upper limit of normal range.
- •MRI showed no super-iron load in the heart and liver, and no severe cirrhosis.
- •Normal Coagulation.
- •Written, informed consent obtained prior to any study-specific procedures.
排除标准
- •Diagnosis of active malignant disease (other than Bowen disease or cervical cancer); or has family history of cancer.
- •Myelopathy, tumor-related cytogenetic changes or other more severe blood diseases.
- •Has alcoholism experience within 6 months prior to enrollment.
- •History of epilepsy.
- •History of bone marrow transplantation.
- •Existence of an available HLA-identical related donor.
- •Pregnant or lactating females.
- •Subject infected with HIV (HIV 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 stem cells transduced with lentiviral vector carrying the related 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)
Tolerability of transplanted cells that are transduced ex vivo & transplanted in subjects with ß-thalassemia major conditioned with a reduced-intensity non-myeloablative preparative regimen.
时间窗: 1 year
Monitoring the following: The occurrence of insertional oncogenesis, which will be investigated by monitoring peripheral blood cell counts \& leukocyte clonality using PCR and sequencing analysis, and qPCR for vector copy number.
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