Phase I Serum-Free Cultured Thymus Transplantation in DiGeorge Anomaly, IND9836
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 主要终点
- Thymopoiesis or graft rejection on biopsy.
研究概览
简要总结
The study purpose is to determine if thymus tissue cultured in a serum-free (SF) solution is a safe and effective treatment for atypical and typical complete DiGeorge anomaly. [Funding Source - FDA OOPD]
详细描述
Complete DiGeorge anomaly is a congenital disorder characterized by athymia. Without successful treatment, patients remain immunodeficient and usually die by age 2 years. In "typical" complete DiGeorge subjects who have no T cells, thymus transplantation without immunosuppression has resulted in diverse T cell development and good T cell function. In "atypical" complete DiGeorge subjects who have no thymus, a rash, and some T cells that presumably developed extrathymically, thymus transplantation with immunosuppression has resulted in diverse T cell development and good T cell function. Thus far, thymus transplantation studies have used thymus cultured in fetal bovine serum (FBS medium). This protocol's purpose is to determine whether transplanted thymus cultured in serum free medium can safely support thymopoiesis and T cell reconstitution as does FBS medium cultured thymus tissue in DiGeorge anomaly subjects. This protocol includes 2 arms: atypical DiGeorge subjects who will receive immunosuppression and thymus transplantation; and, typical complete DiGeorge subjects who will receive thymus transplantation without immunosuppression. Serum free medium use would reduce concerns of animal product exposure including potential exposure to bovine spongiform encephalopathy(BSE).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Thymus Recipients Inclusion:
- •Complete DiGeorge anomaly diagnosis
- •Must have one of following:
- •congenital heart disease
- •hypocalcemia requiring replacement
- •22q11 or 10p13 hemizygous
- •Atypical Arm:
- •Must have, or have had, rash. If rash present, skin biopsy must show T cells. If rash resolved, must have >50/cumm T cells; & <50/cumm naive T cells or <5% total
- •PHA response must be <40000 counts per minute(cpm) on immunosuppression; or, <75000cpm off immunosuppression. PHA test must be done 2x
- •CD45RA+CD62L+ CD3+ T cells must be <50/mm3; or, <5% of total CD
- •Test must be done 2x
- •Typical Arm:
- •PHA response <20 fold or <5,000cpm
- •Circulating CD3+CD45RA+CD62L+T cells <50/mm3 or <5% total T cells
- •2 tests of T cells & PHA response must show similar results
- •Biological Mother Inclusion:
- •Must be recipient's biological mother
- •Thymus Recipient
排除标准
- •Heart surgery <4 weeks pre-transplant or within 3 months post-transplant
- •Rejection by surgeon or anesthesiologist as surgical candidates
- •Lack of sufficient muscle tissue to accept transplant
- •Medical condition does not allow to undergo a biopsy
- •CMV(>500 copies/ml blood by PCR on 2 tests)
- •Ventilator dependence
- •Maternal T cells >20% of total T cells
- •Prior immune reconstitution attempts (e.g., BMT, prior thymus transplant)
- •Hypoparathyroidism meeting criteria for combined thymus/parathyroid transplant & parents desiring it
- •RSV or parainfluenza virus
- •Enterovirus or Adenovirus in stool
- •Biological Mother Exclusion:
- •Unwillingness to sign consent or provide blood/buccal samples
研究组 & 干预措施
Atypical Complete DiGeorge
Thymus Transplantation with Immunosuppression
干预措施: Serum Free Thymus Transplantation with Immunosuppression (Biological)
Typical Complete DiGeorge
Thymus Transplantation without Immunosuppression
干预措施: Serum Free Thymus Transplantation without immunosuppression (Other)
结局指标
主要结局
Thymopoiesis or graft rejection on biopsy.
时间窗: Two months post-thymus transplantation.
Graft rejection analysis by biopsy at 2 months post-thymus transplantation.
Incidence of graft-versus-host-disease (GVHD).
时间窗: One year post-thymus-transplantation.
Development of graft versus host disease in first year after transplantation associated with T cells from the thymus donor.
Survival
时间窗: One year post-thymus transplantation.
Survival at one year post thymus transplantation.
次要结局
- Immune outcomes: T cell development; evaluate T cell numbers, diversity, and function.(One year post-thymus transplantation.)
- Incidence of autoimmune disease.(By two years post-thymus transplantation.)