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Serum-Free Thymus Transplantation in DiGeorge Anomaly

Phase 1
Terminated
Conditions
DiGeorge Anomaly
Interventions
Biological: Serum Free Thymus Transplantation with Immunosuppression
Other: Serum Free Thymus Transplantation without immunosuppression
Registration Number
NCT00849888
Lead Sponsor
Sumitomo Pharma Switzerland GmbH
Brief 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).

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
2
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Atypical Complete DiGeorgeSerum Free Thymus Transplantation with ImmunosuppressionThymus Transplantation with Immunosuppression
Typical Complete DiGeorgeSerum Free Thymus Transplantation without immunosuppressionThymus Transplantation without Immunosuppression
Primary Outcome Measures
NameTimeMethod
Thymopoiesis or graft rejection on biopsy.Two months post-thymus transplantation.

Graft rejection analysis by biopsy at 2 months post-thymus transplantation.

Incidence of graft-versus-host-disease (GVHD).One year post-thymus-transplantation.

Development of graft versus host disease in first year after transplantation associated with T cells from the thymus donor.

SurvivalOne year post-thymus transplantation.

Survival at one year post thymus transplantation.

Secondary Outcome Measures
NameTimeMethod
Immune outcomes: T cell development; evaluate T cell numbers, diversity, and function.One year post-thymus transplantation.

Number of naïve CD4 T cells at one year after transplantation Number of total CD4 T cells at one year after transplantation Proliferative response to PHA at one year after transplantation TCRBV diversity by spectratyping measured by DKL score at one year after transplantation

Incidence of autoimmune disease.By two years post-thymus transplantation.

Incidence of autoimmune disease by year 2 after transplantation Cytopenias as assessed by complete blood counts and differential. Thyroid disease as assessed by thyroid function tests

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