Thymus Transplantation With Immunosuppression

Phase 1

Completed

• Conditions: DiGeorge Anomaly; DiGeorge Syndrome; Complete DiGeorge Anomaly; Complete DiGeorge Syndrome
• Interventions: Biological: Thymus Tissue for Transplantation

• Registration Number: NCT00579709
• Lead Sponsor: Sumitomo Pharma Switzerland GmbH

Brief Summary

The research purpose is to determine if thymus transplantation with immunosuppression is a safe and effective treatment for complete DiGeorge anomaly. The research includes studies to evaluate whether thymus transplantation results in complete DiGeorge anomaly subjects developing a normal immune system.

Detailed Description

DiGeorge anomaly is a complex of cardiac defects, parathyroid deficiency, and thymus absence, resulting in profound T-cell deficiency. There is a spectrum of disease in DiGeorge anomaly with respect to all three defects. For complete DiGeorge anomaly subjects with severe T cell defect, the PI had shown that thymus transplantation is safe and efficacious without pretransplantation immunosuppression and with pretransplantation Thymoglobulin and cyclosporine.

Some DiGeorge patients have very poor T cell function and are at risk of death from infection or other immune problems; however, these patients have enough T cell function to reject grafts. This protocol was designed for these patients. Atypical phenotype and some typical phenotype DiGeorge subjects were included in this protocol.

Atypical complete DiGeorge anomaly patients have rash, lymphadenopathy, and oligoclonal T cell proliferations. The T cells have no markers of thymic function (they do not co-express CD45RA and CD62L; they do not contain T cell receptor rearrangement excision circles, TRECs).

Typical complete DiGeorge anomaly patients in this protocol are those whose PHA response \>20 fold. Although these patients have very low T cell function, it may be enough to reject a transplant, so Thymoglobulin was used.

Study Timeline

• Study Start: 2002-07
• Primary Completion: 2006-12
• Study First Submitted: 2007-12-20
• Study First Submitted QC: 2007-12-20
• Study First Posted: 2007-12-24
• Study Completion: 2019-12
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-23
• Last Update Posted: 2022-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Thymus Tissue for Transplantation	Thymus Tissue for Transplantation

Primary Outcome Measures

Name	Time	Method
Safety & tolerability of Thymoglobulin and cyclosporine followed by thymus transplantation: Survival at 1 year post-transplantation.	1 year post-transplantation

Secondary Outcome Measures

Name	Time	Method
Allograft biopsy used to evaluate graft rejection	2 to 4 months post-transplant	Evidence of thymus allograft rejection by immunohistochemistry of biopsy
Use of additional post transplant immunosuppression after that listed in the protocol.	The post thymus transplantation period	Use of additional post transplant immunosuppression after that listed in the protocol.
CD3 count	10 - 14 months post-transplantation	CD3 count in cells/mm3
CD8 count	10-14 months after thymus transplantation	CD8 count in cells/mm3
Thymopoiesis	2-4 months after thymus transplantation	Evidence of thymopoiesis in thymus allograft by immunohistochemistry of a biopsy
CD4 count	10-14 months after thymus transplantation	CD4 count in cells/mm3
naive CD4 count	10-14 months after thymus transplantation	naive CD4 count in cells/mm3
naive CD8 count	10-14 months after thymus transplantation	naive CD8 count in cells/mm3

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States