Thymus Transplantation With Immunosuppression (884)
The purpose of this research 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.
Complete DiGeorge Anomaly
Complete DiGeorge Syndrome
Biological: Thymus Tissue for Transplantation
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Thymus Transplantation With Immunosuppression, #884|
- Safety & tolerability of Thymoglobulin and cyclosporine followed by thymus transplantation: Survival at 1 year post-transplantation. [ Time Frame: 1 year post-transplantation ] [ Designated as safety issue: Yes ]
- Use of additional post transplant immunosuppression after that listed in the protocol. [ Time Frame: The post thymus transplantation period ] [ Designated as safety issue: No ]Use of additional post transplant immunosuppression after that listed in the protocol.
- Allograft biopsy used to evaluate graft rejection [ Time Frame: 2 to 4 months post-transplant ] [ Designated as safety issue: No ]Evidence of thymus allograft rejection by immunohistochemistry of biopsy
- CD3 count [ Time Frame: 10 - 14 months post-transplantation ] [ Designated as safety issue: No ]CD3 count in cells/mm3
- Thymopoiesis [ Time Frame: 2-4 months after thymus transplantation ] [ Designated as safety issue: No ]Evidence of thymopoiesis in thymus allograft by immunohistochemistry of a biopsy
- CD4 count [ Time Frame: 10-14 months after thymus transplantation ] [ Designated as safety issue: No ]CD4 count in cells/mm3
- CD8 count [ Time Frame: 10-14 months after thymus transplantation ] [ Designated as safety issue: No ]CD8 count in cells/mm3
- naive CD4 count [ Time Frame: 10-14 months after thymus transplantation ] [ Designated as safety issue: No ]naive CD4 count in cells/mm3
- naive CD8 count [ Time Frame: 10-14 months after thymus transplantation ] [ Designated as safety issue: No ]naive CD8 count in cells/mm3
|Study Start Date:||July 2002|
|Estimated Study Completion Date:||June 2027|
|Primary Completion Date:||December 2006 (Final data collection date for primary outcome measure)|
Thymus Tissue for Transplantation
Biological: Thymus Tissue for Transplantation
3 Thymoglobulin doses given prior to thymus tx. Atypical subjects given Cyclosporine (Csa) pre-tx. Desired Csa concentration 180-300ng/ml. If post-tx T cell count remained <4000/cumm Csa weaned over 8 weeks. If T cell >4,000/cumm, Csa held at 180-300ng/ml.
Thymus tissue, donor, & mother of donor were screened for transplant safety. In operating room, thymic slices were transplanted into quadriceps muscle in 1 or both legs.
Subjects had routine blood research immune evaluations. 2-3 months post-tx, open biopsy of allograft. Immune blood studies continued on surviving subjects until January 2010. Biological Mother: Mother provided blood sample used for DNA extraction, to identify/look for maternal T cell presence in recipient pre-tx, and/or for immune testing post-tx.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00579709
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||M. Louise Markert, MD, PhD||Duke University Medical Center, Pediatrics, Allergy & Immunology|