Parathyroid and Thymus Transplantation in DiGeorge #931

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00566488
• Date of registration: 30/11/2007
• Prospective Registration: No
• Primary sponsor: M. Louise Markert
• Public title: Parathyroid and Thymus Transplantation in DiGeorge #931
• Scientific title: Parathyroid and Thymus Transplantation in DiGeorge Syndrome, #931
• Date of first enrolment: January 2005
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00566488
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: M. Louise Markert, MD, PhD
• Affiliation: Duke University Medical Center, Pediatrics, Allergy & Immunology

Key inclusion & exclusion criteria

Transplant Inclusion:

- Complete DiGeorge syndrome (typical or atypical) - may have DiGeorge as part of 22q11
hemizygosity, CHARGE association, or diabetic embryopathy or they may have no
associated syndromes.

- Must have 1 of following:

- Circulating CD3+ T cells < 50/mm3; or

- Circulating CD3+ T cells that also positive for CD45RA and CD62L must be <50/mm3
or must be < 5% of total T cells.

- Must be <24 months old

- Laboratory studies must be done w/in 1 month of treatment:

- Thyroid studies - if abnormal must be on therapy, if recommended by
endocrinology:

- PT and PTT must be <2x upper limits of normal (ULN)

- Absolute neutrophil count must be >500/mm3

- Platelet count must be >50,000/mm3

- AST and ALT must be <5x ULN

- Creatinine must be <1.5 mg/dl

- Parents must agree to have infant stay in Durham until thymus biopsy is done 2-3
months post-treatment.

- Typical subjects must not have a rash with T cells on biopsy nor lymphadenopathy.

- Atypical subjects have rash with T cells on biopsy; may have lymphadenopathy.

- PHA proliferative responses must be tested 2x • Atypical: PHA response must be
<75,000cpm on 2 tests; test can be done while on immunosuppression.

Additional Criteria for Parathyroid Treatment Inclusion

- Hypoparathyroidism

- At least 1 parent must agree to be parathyroid donor

- Must require calcium supplementation to maintain ionized calcium >1.0 mmol/L.
Alternatively, intact PTH must be mmol/L. (Intact PTH measured 2x pre-treatment.)

DiGeorge Treatment Exclusion:

- Heart surgery conducted <4 weeks pre-treatment

- Heart surgery anticipated w/in 3 months of treatment

- Rejection by surgeon or anesthesiologist as surgical candidate

- Lack of sufficient muscle tissue to accept 0.2gms/kg treatment

- Prior attempts at immune reconstitution, such as bone marrow treatment or previous
thymus treatment

- Doesn't commit to remaining at Duke until thymus allograft biopsy

Parathyroid Donor Inclusion:

- Serum calcium in normal range

- Normal parathyroid hormone function

- HLA typing must be consistent with parentage.

- Must not be on anticoagulation or can come off

- Parent chosen for donation will be the 1 sharing most HLA alleles with thymus donor

- HLA-DR matching preferred over HLA class I matching. If there no HLA matching at all,
then either parent will be acceptable if meets other criteria.

- Negative for EBV; CMV; HIV-1; Syphilis; West Nile virus; Hepatitis B; Hepatitis C;
pregnancy; & evidence of head/neck infection

- Fiberoptic nasolaryngoscopy shows vocal cords functioning normally.

- Normal thyroid function

- No history of cancer

- The infant-recipient has 2 living involved parents.

Parathyroid Donor Exclusion:

- Infant recipient doesn't have 2 living involved parents

- Animal tissue/organ recipient

- EBV

- CMV

- HIV-1

- Syphilis

- West Nile virus

- Hepatitis B

- Hepatitis C

- Pregnant

- Evidence of head/neck infection

- Vocal cords not functioning normally.

- Thyroid abnormalities

- Hyperparathyroidism

- History of cancer

- Mad cow disease (positive)

- SARS(and exposure)

- Smallpox exposure

Biological Mother of DiGeorge Subjects Inclusions:

Mother must be competent to consent or assent to study participation and willing to provide
blood sample. No other inclusion/exclusion.



Age minimum: N/A
Age maximum: 24 Months
Gender: All

Health Condition(s) or Problem(s) studied

Complete DiGeorge Syndrome

Hypoparathyroidism

DiGeorge Syndrome

Intervention(s)

Biological: Thymus/Parathyroid Transplantation

Primary Outcome(s)

Efficacy parameter: use of calcium/calcitriol at 1 year post-transplantation. [Time Frame: 1 year after thymus transplantation]

Secondary Outcome(s)

Efficacy parameters: spectra typing at 1 year post transplantation [Time Frame: approximately 1 year after thymus transplantation (12.1 to 18.0 months after transplantation)]

Efficacy parameters: proliferative response to phytohemagglutinin [Time Frame: approximately 1 year after thymus transplantation (8.9 to 17.8 months after transplantation)]

Efficacy parameters: CD3 count [Time Frame: 10-14 months after thymus transplantation]

Efficacy parameters: CD4 count [Time Frame: 10-14 months after thymus transplantation]

Efficacy parameters: CD8 count [Time Frame: 10-14 months after thymus transplantation]

Efficacy parameters: naive CD8 count [Time Frame: 10-14 months after thymus transplantation]

Efficacy parameters: naive CD4 count [Time Frame: 10-14 months after thymus transplantation]

Efficacy parameters: proliferative response to tetanus toxoid [Time Frame: approximately 1 year after thymus transplantation (8.9 to 17.8 months after transplantation)]

Efficacy parameters: ionized calcium [Time Frame: 10-14 months after thymus transplantation]

Secondary ID(s)

R01AI054843

3R56AI047040-11A1S1

FDA-FD-R-002606

5K12HD043494-09

#931

Pro00016482

2R01AI047040-11A2

R01AI047040

R56 Bridge R01AI4704011A1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Enzyvant Therapeutics GmbH

Food and Drug Administration (FDA)

National Institute of Allergy and Infectious Diseases (NIAID)

National Institutes of Health (NIH)