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 T cells, which fight infection. Complete DiGeorge anomaly patients cannot fight infection and are immunodeficient. Without successful treatment, cDGA patients usually die by age 2 years. Thymus transplantation with and without immunosuppression (drugs given before and after transplantation) has resulted in the development good T cell function in complete DiGeorge anomaly subjects. This expanded access study continues thymus transplantation safety and efficacy research for the treatment of complete DiGeorge anomaly. Eligible participants undergo thymus transplantation. Immune function testing is continued for one year post-transplantation.
Full Title of Study: “Safety and Efficacy of Thymus Transplantation in Complete DiGeorge Anomaly, IND#9836”
- Study Type: Expanded Access
Complete DiGeorge anomaly (cDGA) is a congenital disorder characterized by athymia. Without successful treatment, children remain immunodeficient and usually die by age 2 years. In complete DiGeorge subjects, thymus transplantation 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 thymus transplantation safety and efficacy research for the treatment of complete DiGeorge anomaly. Until thymus transplantation is FDA approved as standard care for complete DiGeorge anomaly, 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 undergo thymus transplantation and may undergo an allograft biopsy. Protocol specified studies continue until approximately one year post-transplantation. Study participation lasts two years or until thymus recipients may be asked to participate in a long-term follow-up study.
- Biological: Thymus Tissue for Transplantation
- Potential thymus recipient subjects are screened for eligibility. Thymus tissue (unrelated donor), donor, & donor’s mother screened for safety. Thymus transplantation is done under general anesthesia in the operating room. Thymus tissue is transplanted into the subject’s quadriceps. Two to three months post-transplantation, if medically stable, the subject may undergo allograft biopsy. Subjects undergo laboratory testing for approximately one-year post-transplantation. At approximately year 2 post-transplantation, subjects are contacted for data collection.
- Procedure: Blood Draw
- Drug: Rabbit anti-thymocyte globulin
- Three doses of 2 mg/kg IV prior to thymus transplantation for immune suppression groups 2, 3, and 4. Each dose is given over 12 hours. RATGAM is usually given on days -5, -4, and -3 prior to thymus transplantation.
- Drug: Cyclosporine
- Csa may be given every 8 to 12 hours orally or IV before and after thymus transplantation for immune suppression groups 3 and 4. The Csa dose is dependent on T cell numbers and the target CSA trough levels. Csa is weaned as per protocol.
- Drug: Tacrolimus
- If unable to tolerate cyclosporine, then FK506 is given. FK506 may be given every 8 to 12 hours orally or IV before and after thymus transplantation. FK506 dose is dependent on T cell numbers and the target FK506 trough levels. FK506 is weaned as per protocol.
- Drug: Methylprednisolone or Prednisolone
- Steroids IV or orally may be given before and/or after thymus transplantation. Administration and dosage depends on T cell numbers. Steroids are weaned as per protocol.
- Drug: Basiliximab
- A single dose of Basiliximab 5 mg/kg IV may be given. Administration of Basiliximab depends on T cell numbers and T cell activation. A single dose of Basiliximab may be given after the administration of rabbit anti-thymocyte globulin and before thymus transplantation. If Basiliximab is not given before thymus transplantation, and, depending on the T cell numbers and T cell activation, a single dose of Basiliximab may be given 3 to 5 days after thymus transplantation.
- Drug: Mycophenolate mofetil
- Mycophenolate mofetil (MMF) may be given if the T cell count remains elevated 5 days after thymus transplantation. If MMF is given, the dose is 15 mg/kg/dose every 8 hours IV or orally. MMF may be stopped at 35 days or continued for up to six months after thymus transplantation.
Participating in This Clinical Trial
- Must have 1 of following: 22q11 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 PHA response < 5,000 cpm and < 20 fold PHA response. Group 2 •Typical cDGA whose T cells have a PHA response >5,000 cpm and <50,000 cpm and >20 fold PHA response Group 3 – Typical cDGA whose T cells have PHA response >50,000 cpm – Typical cDGA with maternal engraftment – Atypical cDGA whose T cells have PHA response <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 >75,000cpm while on no immunosuppression or PHA responses >40,000cpm while on immunosuppression – Atypical cDGA with maternal engraftment and group 4 PHA response Transplant Exclusion: – Heart surgery <4 wks pre-transplantation – Heart surgery anticipated w/in 3 months after proposed transplantation – Rejection by surgeon or anesthesiologist as surgical candidate – Lack of sufficient muscle tissue to accept transplant of 2,000 mm2/m2 body surface area – HIV infection – Prior attempts at immune reconstitution, such as bone marrow transplant or previous thymus transplant – CMV on 2 tests for Groups 2, 3, and 4
Gender Eligibility: All
Minimum Age: N/A
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- M. Louise Markert
- National Institutes of Health (NIH)
- Provider of Information About this Clinical Study
- Sponsor-Investigator: M. Louise Markert, Professor of Pediatrics – Duke University
- Overall Official(s)
- M. Louise Markert, M.D., Ph.D, Principal Investigator, Duke University Medical Center, Pediatrics, Allergy & Immunology
- Overall Contact(s)
- M. Louise Markert, M.D., Ph.D, 919-684-6263, email@example.com
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