Overview

This trial is active, not recruiting.

Conditions digeorge syndrome, complete typical digeorge anomaly
Treatment thymus tissue for transplantation
Phase phase 2
Sponsor M. Louise Markert
Collaborator National Institutes of Health (NIH)
Start date November 2001
End date February 2008
Trial size 26 participants
Trial identifier NCT00576407, 2R01AI047040-11A2, 3R56AI047040-11A1S1, 5K12HD043494-09, Pro00009955 #668, R01AI047040, R01AI054843, R56 Bridge R01AI4704011A1

Summary

The study purpose is to determine whether thymus transplantation without immunosuppression is effective in treating typical complete DiGeorge syndrome.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Thymus Tissue for Transplantation in Complete DiGeorge Syndrome
thymus tissue for transplantation Thymus Tissue
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.

Primary Outcomes

Measure
Survival rate at one year post-transplantation.
time frame: One year post-transplantation.

Secondary Outcomes

Measure
T cell proliferative response to tetanus toxoid
time frame: Approximately 1 year after transplantation

Eligibility Criteria

Male or female participants of any age.

Inclusion Criteria: - Diagnosis of complete DiGeorge syndrome which is either: T cells with < 50/mm3 with naive phenotype; or < 5% CD3 + T cells with naive T cell phenotype. - Diagnosis of typical DiGeorge syndrome phenotype: < 50 T cells/cumm and very low proliferative responses to mitogens (e.g. < 20 fold response to mitogen phytohemagglutinin). - Proliferative response to PHA < 20 fold above background or < 5000 counts per minute(cpm), whichever is higher. {Note: Subjects with PHA responses 20 fold or more over background or > 5,000 cpm, whichever is higher, may be enrolled in another thymus transplant protocol.} - Must have heart disease; hypocalcemia requiring replacement; 22q11 or 10p13 hemizygosity; CHARGE association; or must be child of diabetic mother and have abnormal ears. Exclusion Criteria: - Those who do not meet inclusion criteria - Atypical DiGeorge syndrome phenotype - Rash indicating atypical DiGeorge syndrome phenotype. Transplant Exclusion: - Heart surgery <4 weeks pre-tx date - Heart surgery anticipated w/in 3 months of proposed tx - Rejection by surgeon or anesthesiologist as surgical candidates - Lack of sufficient muscle tissue to accept 0.2 grams/kg transplant

Additional Information

Official title Phase II Study of Thymus Transplantation in Complete DiGeorge Syndrome #668
Principal investigator M. Louise Markert, MD, PhD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Duke University.