Thymus Transplantation in DiGeorge Syndrome #668
|DiGeorge Syndrome Complete Typical DiGeorge Anomaly||Biological: Thymus Tissue for Transplantation||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Thymus Transplantation in Complete DiGeorge Syndrome #668|
- Survival rate at one year post-transplantation. [ Time Frame: One year post-transplantation. ]
- T cell proliferative response to tetanus toxoid [ Time Frame: Approximately 1 year after transplantation ]Proliferative response that is 10 fold over background
|Study Start Date:||November 2001|
|Estimated Study Completion Date:||June 2027|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
Thymus Tissue for Transplantation in Complete DiGeorge Syndrome
Biological: Thymus Tissue for Transplantation
Thymus transplantation is done using allogeneic cultured postnatal tissue from unrelated donors. Thymus tissue, the donor, & donor's mother were screened for safety. Approximately 2-3 weeks post-harvest thymus slices were transplanted into the recipient's quadriceps. Dose is number of grams of transplanted tissue divided by the recipient's weight in kilograms. Minimum dose was 4 g/m2. Maximum dose 18g/m2. At time of transplantation, a skin biopsy was obtained to look for preexisting T cells. 2-3 months post-transplant allograft biopsy to evaluate for thymopoiesis & graft rejection. At time of biopsy, skin biopsy done to look for T cell clonal populations. Post-transplant, subjects followed by routine research immune evaluations, using blood samples for 2 years.
There is no safe and effective treatment for DiGeorge syndrome and most patients die by the age of two. Complete DiGeorge syndrome is characterized by very low T cell or very low naïve T cell numbers. In this study, typical complete DiGeorge syndrome subjects received human postnatal cultured thymus tissue transplants. Thymus tissue that would otherwise be discarded was transplanted into DiGeorge subjects in the operating room. At the time of transplantation, a skin biopsy was obtained to look for any preexisting T cells. After transplantation, subjects were followed by routine research immune evaluations, using blood samples obtained every 2-4 weeks. At approximately 2-3 months post-transplantation subjects underwent an open biopsy of the allograft. The biopsy was done under general anesthesia in the operating room. At the time of the graft biopsy, another skin biopsy was obtained to look for clonal populations of T cells.
The protocol aims include: assessing thymopoiesis in the allograft biopsy; assessing immunoreconstitution of complete DiGeorge syndrome subjects after postnatal allogeneic thymus transplantation; assessing minimally invasive methods of assessing thymopoiesis (flow cytometry and polymerase chain reaction (PCR); assessing pre-transplant T cells which do not proliferate in response to mitogens (focusing on NK-T cells); and, assessing thymus transplantation safety and toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00576407
|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|