NCT00849888

Serum-Free Thymus Transplantation in DiGeorge Anomaly

Phase I Serum-Free Cultured Thymus Transplantation in DiGeorge Anomaly, IND9836

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Sumitomo Pharma Switzerland GmbH · Industry
• Sex: All
• Age: 2 Years
• Healthy volunteers: Not accepted

Summary

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. \[Funding Source - FDA OOPD\]

Detailed description

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).

Conditions

• DiGeorge Anomaly

Interventions

Type	Name	Description
BIOLOGICAL	Serum Free Thymus Transplantation with Immunosuppression	Cyclosporine pre-transplant (trough 180-220ng/ml) until naive T cells develop. Subjects \>4,000/cumm T cells, pre-transplant methylprednisolone or prednisolone 1-2mg/kg/day. All subjects pre-transplant days -5,-4,-3: 3 doses 2mg/kg rabbit anti-thymocyte globulin. Thymus tissue (unrelated donor), donor, \& donor's mother screened for safety. Transplant under general anesthesia into quadriceps. First 2 subjects, FBS cultured thymus is transplanted in 1 leg \& serum free (SF) in other. After first 2 subjects \>10% naïve T cells, 3rd receives only SF thymus. After 3rd subject \>10%naive T cells, 4th subject transplanted. Thymus dose 4-18 grams/m2 body surface area. Thymus biopsy 8-12 weeks post-transplant. Skin biopsy at time of transplant \& thymus biopsy. Followed by immune evaluations.
OTHER	Serum Free Thymus Transplantation without immunosuppression	Thymus tissue (unrelated donor), donor, \& donor's mother screened for safety. Transplant under general anesthesia into quadriceps. First 2 subjects: FBS cultured thymus transplanted in 1 leg \& serum free cultured thymus in other leg. After first 2 subjects have thymopoiesis in serum-free biopsy, \>10% naïve T cells, 3rd subject receives only serum free cultured thymus. After 3rd subject \>10% naive T cells, 4th subject receives transplant of only serum free cultured thymus. Dose 4-18grams/m2 body surface area. At time of transplant, skin biopsy. Allograft biopsy \& skin biopsy done 8 to 12 weeks post-transplant. (Graft biopsy not done if subject medically unstable.) Post-transplant, subjects followed by immune evaluations, using blood samples, for two years.

Timeline

• Start date: 2008-04-01
• Primary completion: 2011-02-01
• Completion: 2011-02-01
• First posted: 2009-02-24
• Last updated: 2022-04-01