This trial is active, not recruiting.

Conditions digeorge syndrome, digeorge anomaly, complete digeorge anomaly, complete digeorge syndrome
Treatment thymus tissue for transplantation
Phase phase 1
Sponsor M. Louise Markert
Collaborator National Institutes of Health (NIH)
Start date July 2002
End date December 2006
Trial size 15 participants
Trial identifier NCT00579709, #884, 2R01AI047040-11A2, 3R56AI047040-11A1S1, 5K12HD043494-09, Pro00013734, R01AI047040, R01AI054843, R56 Bridge R01AI4704011A1


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.

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
Thymus Tissue for Transplantation
thymus tissue for transplantation IND 9836
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.

Primary Outcomes

Safety & tolerability of Thymoglobulin and cyclosporine followed by thymus transplantation: Survival at 1 year post-transplantation.
time frame: 1 year post-transplantation

Secondary Outcomes

Use of additional post transplant immunosuppression after that listed in the protocol.
time frame: The post thymus transplantation period
Allograft biopsy used to evaluate graft rejection
time frame: 2 to 4 months post-transplant
CD3 count
time frame: 10 - 14 months post-transplantation
time frame: 2-4 months after thymus transplantation
CD4 count
time frame: 10-14 months after thymus transplantation
CD8 count
time frame: 10-14 months after thymus transplantation
naive CD4 count
time frame: 10-14 months after thymus transplantation
naive CD8 count
time frame: 10-14 months after thymus transplantation

Eligibility Criteria

Male or female participants of any age.

Transplant Inclusion - No age limit - Thyroid studies must be done and if abnormal, must be on therapy DiGeorge diagnosis - must have 1 symptom from the following list: - Heart defect - Hypocalcemia requiring replacement - 22q11 hemizygosity - 10p13 hemizygosity - CHARGE association - Abnormal ears plus mother with diabetes (type I, type II, or gestational) Atypical Diagnosis: - Must have, or have had, a rash. If rash present, biopsy of rash must show T cells in skin. If rash & adenopathy resolved, must still have oligoclonal T cells. - Within 1 month of tx must have PHA response >20 fold above background or >5,000 cpm, whichever is higher, or response can be < this. - Circulating CD3+ T cells >50/mm3 but CD45RA+CD62L+CD3+ T cells <50/mm or <5% of CD3 count, whichever is higher (must be done 2x) - Immunoscope with >40% oligoclonal TCRBV families. A 2nd test per sponsor discretion if T cell numbers increase or activation status changes. - If TREC done pre-tx must have TRECs <100 per 100,000 CD3+ cells. Typical Diagnosis: - Circulating CD3+ CD45RA+ CD62L+ T cells and <50/mm3 or <5% of total T cells - PHA response >20 fold above background or >5,000 cpm, whichever is higher. - 2 studies must show similar immunological findings qualify for this study. - TRECs, if done, should be <100/100,000 CD3 cells 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 Thymus Transplantation With Immunosuppression, #884
Principal investigator M. Louise Markert, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Duke University.