Safety and Efficacy of Lentiviral Vector Transduction of β-globin Genetically Modified Autologous CD34+ Hematopoietic Stem Cells in Patients With Transfusion-dependent β-thalassemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Red blood cell (RBCs) transfusion requirements, whether reaching TI
研究概览
简要总结
This study will be intented to evaluate the safety, tolerability, and engraftment efficacy after myeloablative preconditioning and transplantation of autologous CD34+ hematopoietic stem cells transduced with a lentiviral vector encoding the human βA-T87Q-globin gene in patients with transfusion-dependent (TDT) β-thalassemia.
详细描述
This is an open-label, single-dose study of BD211 in patients with transfusion-dependent β-thalassemia aged 6 to 35 years. It is estimated that 10 subjects will be enrolled. BD211 is a gene modified gene therapy product designed to produce healthy β-globin in red blood cells in beta-thalassemia patients. The total follow-up duration was 24 months, the safe endpoints and effectiveness endpoints will be used to assess the safety and efficacy profiles in patients with transfusion-dependent β-thalassemia.
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
- 6 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 6 to 35 years old, including:
- •Subjects should be able to provide an ICF. Diagnosed as Transfusion Dependent β-thalassemia with any genotype (β0, β+, βE/β0, βS/S, βS/β0, βS/β+), confirmed the Hb analysis. No alfa chain genetic abnormalities. Subjects must stabilize and maintain an appropriate iron chelation regimen. Transfusion-dependent types are defined as requiring at least 100 mL/kg/ year of red blood cells (pRBCs).
- •The tumor genes chip detection results about acute leukemia and myeloid tumor gene mutations (panel) showed no abnormality.
- •There were candidates for HLA gene semi-compatible hematopoietic stem cell transplantation.
- •No eligiblity for allogeneic hematopoietic stem cell transplantation.
- •The treatment of erythrocyte maturation agent luspatercept cannot be financially supported.
- •The investigator confirmed that subject was willing to follow the research procedures.
- •Having complete medical records including a history of blood transfusions testified subject received treatment and followed up for at least two years prior to screening.
排除标准
- •Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
- •HIV-1 and HIV-2 were positive, and / or HTLV-1, HTLV-2 and VSV-G antibodies were positive.
- •An active bacterial, viral, fungal or parasitic infection.
- •Contraindicated for the extraction of bone marrow under anesthesia.
- •Any malignancy, myeloproliferative, or immunodeficient disease and relevant medical history.
- •Peripheral blood white blood cell (WBC) count < 3×10^9/L or platelet count < 120×10^9/L.
- •A history of allo-transplantation.
- •Erythropoietin was used within 3 months prior to HSC cell collection.
- •Immediate family members with known or suspected familial cancer syndromes (including but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers).
- •Subjects with a diagnosis of major mental illness may had a serious disability to participate in the study.
- •Active recurrent malaria.
- •Pregnant or postpartum nursing or unable to use contraception.
- •History of major organ injury including:
- •Liver disease, transaminase > 3 times the upper limit of normal. (If the liver biopsy does not reveal evidence of widespread bridging fibrosis, cirrhosis, or acute hepatitis, this indicator will not be used as a criterion for the exclusion); Widely bridging fibrosis, histopathological evidence of acute hepatitis or cirrhosis showed in liver biopsy Heart disease, left ventricular ejection fraction < 25%; Kidney disease, creatinine clearance < 30% normal level; Of severe iron overload, confirmed by the study doctor; An heart MRI detection of T2 * < 10 ms; Significant pulmonary hypertension needing clinical medical intervention.
- •Any other conditions being ineligible for HSC transplantation determined by the investigator.
- •The subject involved with another clinical study in a 30-day screening period.
- •Subjects who expected to become parents during the 27-month study period.
- •Prior treatment with any type of gene and/or cell therapy.
- •As assessed by the investigator, the subjects or their parents are unable to comply well with the study procedures per protocol.
- •Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.
结局指标
主要结局
Red blood cell (RBCs) transfusion requirements, whether reaching TI
时间窗: 24 months
Comparison of blood volume and number of transfusions in the 2 years prior to participants enrolment as baseline with blood volume and number of transfusions up to months 6, 12, and 24 after receiving transfusion of the BD211. TI defined as peripheral blood weighted average hemoglobin (Hb) \> or = 9 g/dL without pRBCs transfusion for 60 days after BD211 treatment, and transfusion is continuously halted for 12 months.
Total hospitalizing days at 6, 12, and 24 months (discharge after transplant)
时间窗: 24 months
Total hospitalizing days at 6, 12, and 24 months after transplantation were counted.
次要结局
- Percentage of treated participants with Transfusion-Dependent β-Thalassemia (TDT) who achieved transfusion independence for at least 6 months(24 months)
- Neutrophil engraftment, platelet engraftment and vector copy number(24 months)
- Change in ferritin/liver iron levels from baseline(24 months)
- RCL incidence(24 months)
- Characterized insertion mutagenesis events that lead to clonal dominance or leukemia(24 months)
- Frequency and severity of AE(24 months)
- Change in RBCs infusion from baseline at 6 to 24 months(24 months)
- Mean Hb (g/dL) at 6, 12 and 24 months after treatment(24 months)
- Transplant-related mortality in 3 months and 12 months(12 months)
- Overall survival(24 months)