Thymus Transplantation Safety-Efficacy

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Complete DiGeorge Anomaly DiGeorge Syndrome DiGeorge Anomaly Complete DiGeorge Syndrome	Biological: Cultured Thymus Tissue Procedure: Blood Draw Drug: Rabbit anti-thymocyte globulin Drug: Cyclosporine Drug: Tacrolimus Drug: Methylprednisolone or Prednisolone Drug: Mycophenolate mofetil

Detailed Description

Complete DiGeorge anomaly (cDGA) is a congenital disorder characterized by athymia. Without successful treatment, patients with cDGA must remain in reverse isolation to prevent infection and subsequent death. In patients with cDGA, implantation of cultured thymus tissue with and without immunosuppression has resulted in diverse T cell development and good T cell function.

The purpose of this expanded access study is to continue cultured thymus tissue safety and efficacy research for the treatment of athymia in patients with cDGA. Until administration of cultured thymus tissue is FDA approved as standard care for cDGA, research study participation is the only means by which a patient may have access to this potentially life-saving procedure.

This protocol includes 4 groups: one for subjects who do not require immunosuppression; and 3 immunosuppression groups for subjects with different T cell function levels to be suppressed adequately.

Eligible subjects receive cultured thymus tissue and may undergo an allograft biopsy.

Protocol specified studies continue until approximately one year post-implantation. Study participation lasts two years.

Study Design

Study Type:

Expanded Access

Official Title:

Safety and Efficacy of Thymus Transplantation in Complete DiGeorge Anomaly, IND#9836

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John W. Sleasman	Durham	North Carolina	United States	27710

Sponsors and Collaborators

Enzyvant Therapeutics GmBH
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)