Thymus Transplantation Safety-Efficacy

• Status: Available
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Complete DiGeorge anomaly (cDGA) is a disorder in which there is no thymus function. With no thymus function, bone marrow stem cells do not develop into educated T cells, which fight infection. Without successful treatment, patients with cDGA must remain in reverse isolation to prevent infection and subsequent death.

Cultured thymus tissue with and without immunosuppression (drugs given before and after implantation) has resulted in the development of good T cell function in subjects with complete DiGeorge anomaly.

This expanded access study continues cultured thymus tissue safety and efficacy research for the treatment of complete DiGeorge anomaly. Eligible participants receive cultured thymus tissue. Immune function testing is continued for one year post-implantation.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M. Louise Markert
• Collaborators: Enzyvant Therapeutics GmbH; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
• Treatments: Antibodies, Monoclonal; Antilymphocyte Serum; Basiliximab; Cyclosporine; Cyclosporins; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Mycophenolate mofetil; Mycophenolic Acid; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Tacrolimus; Thymoglobulin

Criteria

Inclusion criteria for implantation of cultured thymus tissue:

• Must have 1 of following: 22q11.2ds or 10p13 hemizygosity; hypocalcemia requiring replacement; congenital heart disease; or CHARGE syndrome or CHD7 mutation

• Complete DiGeorge: <50 CD3+ T cells/cumm or <50 CD3+ T cells/cumm that are CD62L+ CD45RA+, or <5% of CD3+ cells are CD62L+ CD45RA+

• Atypical DiGeorge subjects must have, or have had, a rash.

Group 1

•Typical cDGA whose T cells have a phytohemagglutinin (PHA) response of < 5,000 counts per minute (cpm) and < 20 fold PHA response.

Group 2

•Typical cDGA whose T cells have a PHA response of >5,000 cpm and <50,000 cpm and >20 fold PHA response.

Group 3

• Typical cDGA whose T cells have a PHA response of >50,000 cpm.

• Typical cDGA with maternal engraftment

• Atypical cDGA whose T cells have a PHA response of <40,000 cpm when on immunosuppression or <75,000 cpm to PHA when not on immunosuppression.

• Atypical cDGA with group 3 PHA response & maternal engraftment

Group 4

• Atypical cDGA with PHA responses of >75,000 cpm while on no immunosuppression or a PHA responses of >40,000 cpm while on immunosuppression.

• Atypical cDGA with maternal engraftment and group 4 PHA response

Exclusion criteria for implantation of cultured thymus tissue:

• Heart surgery conducted less than 4 weeks prior to projected implantation date.

• Heart surgery anticipated within 3 months after the proposed time of implantation

• Rejection by surgeon or anesthesiologist as surgical candidate

• Lack of sufficient muscle tissue to accept a transplant

• HIV infection

• Prior attempts at immune reconstitution, such as bone marrow transplant or previous thymus transplant

• CMV infection: For Groups 2, 3, and 4 CMV infection documented by >500 copies/ml in the blood by PCR on two consecutive assays.

• Ventilator Dependence or Positive Pressure Support: Ventilator support or positive pressure support, such as Continuous Positive Airway Pressure (CPAP) or Bi-level Positive Airway Pressure (BiPAP) support for a condition that is deemed to be severe or irreversible or which renders the subject too clinically unstable to undergo the procedures.