Thymus Transplantation With Immunosuppression (884)

Sumitomo Pharma

Status and phase

Completed

Phase 1

Conditions

DiGeorge Syndrome

DiGeorge Anomaly

Complete DiGeorge Anomaly

Complete DiGeorge Syndrome

Treatments

Biological: Thymus Tissue for Transplantation

Study type

Interventional

Funder types

Industry

NIH

Identifiers

NCT00579709

5K12HD043494-09 (U.S. NIH Grant/Contract)

Pro00013734

R56 Bridge R01AI4704011A1 (Other Grant/Funding Number)

R01AI054843 (U.S. NIH Grant/Contract)

3R56AI047040-11A1S1 (U.S. NIH Grant/Contract)

R01AI047040 (U.S. NIH Grant/Contract)

2R01AI047040-11A2 (U.S. NIH Grant/Contract)

#884

Details and patient eligibility

About

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.

Full 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.

Enrollment

15 patients

Sex

All

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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: