Sleeping Beauty Transposon-Engineered Plasmablasts for Expression and Delivery of Alpha-L-iduronidase in Patients With Hurler Syndrome That Have Previously Undergone Allogeneic Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Safety and Tolerability after Infusion: Incidence of Adverse Events
研究概览
简要总结
This is a single center, Phase 1/2 study in which patients with Hurler syndrome who have previously undergone allogeneic hematopoietic stem cell transplantation are treated with autologous plasmablasts engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty transposon system.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 8 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Mucopolysaccharidosis type IH (MPS IH, Hurler syndrome)
- •Underwent a previous hematopoietic stem cell transplant >1 year prior to study enrollment
- •Age ≥3 years and ≤8 years at time of study registration
- •≥ 10 kilograms body weight
- •Creatinine <1.5 normal for gender and age.
- •Ejection fraction ≥ 40% by echocardiogram
- •Must commit to traveling to the University of Minnesota for the necessary followup evaluations
- •Must agree to stay in the Twin Cities area (<45-minute drive from the Masonic Children's Hospital) for a minimum of 5 days after each cell infusion
- •Voluntary written parental consent prior to the performance of any study related procedures
排除标准
- •Prior enzyme replacement therapy within 4 months prior to enrolling on study
- •History of B cell related cancer, EBV lymphoproliferative disease or autoimmune disorders
- •Evidence of active graft vs. host disease
- •Requirement for systemic immune suppression
- •Requirement for continuous supplemental oxygen
- •Any medical condition likely to interfere with assessment of safety or efficacy of the study treatment.
- •In the investigator's judgement, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.
研究组 & 干预措施
Phase 1: Dose Escalation
干预措施: Autologous Plasmablasts (Drug)
Phase 2 - Expansion at MTD
干预措施: Autologous Plasmablasts (Drug)
结局指标
主要结局
Safety and Tolerability after Infusion: Incidence of Adverse Events
时间窗: 1 Year
Incidence of Adverse Events
Growth Velocity (cm/year)
时间窗: 1 Year
Growth velocity in centimeters/year over a one-year period through determinations of sitting and standing height at baseline and post infusion
Maximum Tolerated Dose (MTD)
时间窗: 1 Year
Maximum tolerated dose (MTD) of autologous plasmablasts engineered to express large amounts of α-L-iduronidase (IDUA) using a Sleeping Beauty transposon approach
次要结局
- Z-score Growth Rate(1 Year)
- Donor Engraftment(Baseline, 6 months and 1 Year)
- Levels of circulating antibodies (IgG, IgM, IgA and IgE)(1 Year)