Thymus Transplantation Dose in DiGeorge #932

• Register: ClinicalTrials.gov
• Last refreshed on: 4 April 2022
• Main ID: NCT00576836
• Date of registration: 17/12/2007
• Prospective Registration: No
• Primary sponsor: Enzyvant Therapeutics GmBH
• Public title: Thymus Transplantation Dose in DiGeorge #932
• Scientific title: Dose Study of Thymus Transplantation in DiGeorge Anomaly, IND 9836, #932.1
• Date of first enrolment: September 2, 2004
• Target sample size: 7
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00576836
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

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

Key inclusion & exclusion criteria

Thymus Transplant Inclusion Criteria:

- A parent or guardian of the DGS subject signed the consent form.

- Medical screening was completed.

- For a diagnosis of DGS, the subject had to have one of the following:

- Congenital heart disease;

- Hypocalcemia requiring replacement;

- 22q11.2 hemizygosity or 10p13 hemizygosity;

- CHARGE association or CHD7 mutation;

- A subject with abnormal ears whose mother had diabetes (type I, type II, or
gestational).

- To meet the criteria of typical complete DiGeorge Anomaly (cDGA), the subject had to
have either:

- Circulating CD3+ T cell count by flow cytometry < 50/mm3 OR

- Circulating CD3+ T cells that were also positive for Cluster of Differentiation
45RA (CD45RA)+ CD62L+ and were < 50/mm3 or less than 5% of total T cells.

Thymus Transplant Exclusion Criteria:

- Had heart surgery less than 4 weeks prior to projected implant date;

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

- Present or past lymphadenopathy;

- Rash associated with T cell infiltration of the dermis and epidermis;

- Rejection by the surgeon or anesthesiologist as surgical candidate;

- Lack of sufficient muscle tissue to accept a transplant of 4 g/m2 body surface area
(BSA) or 0.2 g/kg subject bodyweight;

- Had human immunodeficiency virus (HIV) infection;

- Had prior attempts at immune reconstitution, such as bone marrow transplant or
previous thymus transplantation;

- Ventilator support or positive pressure support: Subjects had to be off ventilator or
other pressure support such as continuous positive airway pressure (CPAP) or bi-level
positive airway pressure (BiPAP) support for 2 weeks prior to enrollment. If the
subject was enrolled and was placed back on ventilator or pressure support, the
subject had to be able to be weaned off and remain off ventilator or pressure support
for 2 weeks. If the subject could not be successfully weaned off ventilator or
pressure support, the subject was to be withdrawn from the study.

Additional Inclusion Criteria for Parathyroid Transplant Recipient:

- 2 tests in patient showing: intact parathyroid hormone (PTH) < 5 pg/ml when ionized
calcium < 1.1 mmol/L

- All inclusion criteria for thymus transplant must be met

- 2 involved parents

Exclusion for Parathyroid Transplant Recipient:

- Parents do not meet enrollment criteria.

- Parent(s) decline to be parathyroid donor(s).

Parental Parathyroid Donor Inclusion:

- > 18 years old

- Answers all questionnaire items and meets safety screening criteria

- Normal serum calcium

- Normal PTH function

- HLA typing consistent with parentage

- Parent chosen for donation will share HLA-DR allele in thymus donor; if not
applicable, then either parent will be selected (if meet all other criteria).

- Must not be on anticoagulation or can come off for donation/transplantation

Parental Parathyroid Donor Exclusion:

- Donor is only living involved parent or caretaker of the recipient

- Hypoparathyroidism - low parathyroid hormone (PTH) in presence of low serum calcium
and high serum phosphate

- Hyperparathyroidism (or history of) - elevated PTH in presence of high serum calcium
and low serum phosphate

- History of cancer

- Evidence of any of following: HIV-1, HIV-2, HTLV-1, HTLV-2, syphilis, hepatitis B,
hepatitis C, West Nile virus, or Trypanosoma Cruzi (Chagas disease)

- Elevated AST, ALT, alkaline phosphatase > 3 times upper limit of normal

- History including receipt of a xenograft or risk factors for SARS, Mad Cow - Disease
or smallpox. Note: if parent has Mad Cow Disease risk factors (but not active
disease), parent(s) may give permission for transplantation.

- CMV positive urine

- Positive CMV IgM antibodies

- Positive IgM anti-EBV VCA

- On blood thinners and cannot stop for the parathyroid donation

- Elevated PT or PTT (> ULN)

- Platelets < 100,000

- Positive Toxoplasma IgM

- The donor will receive a history and physical; may be excluded based on PI's medical
judgment

- Hemoglobin < 9 g/dl

- Infectious lesion on head or neck

- Goiter on ultrasound

- Abnormal fiberoptic laryngoscopy of vocal cords

- Pregnancy

- Positive HSV IgG is not an exclusion; however, post transplantation prophylaxis is
needed

- Positive VZV IgG is not an exclusion; however, post transplantation prophylaxis is
needed

- Medical concern of otolaryngologist

- Concern by medical psychologist or social worker. Parents are interviewed together and
separately regarding following areas: medical history; health habits; substance use;
relationships and support; education/work history; mental status/psychological
history; readiness for donation.

- Questionnaire (safety screening) responses can lead to exclusion.

Biological Mother of DiGeorge Subject Inclusion Criteria:

- Competent to provide consent

- Willing to provide blood for testing (No other inclusion/exclusion for mother)



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

Health Condition(s) or Problem(s) studied

Complete DiGeorge Syndrome

DiGeorge Anomaly

DiGeorge Syndrome

Complete DiGeorge Anomaly

Intervention(s)

Other: Cultured Thymus Tissue Implantation with Parathyroid Transplantation

Biological: Cultured Thymus Tissue Implantation (CTTI)

Primary Outcome(s)

Survival at 1 Year Post-CTTI [Time Frame: 1 year post-CTTI]

Secondary Outcome(s)

Immune Reconstitution Efficacy - CD4 T Cells [Time Frame: 1 year post-CTTI]

Immune Reconstitution Efficacy - CD8 T Cells [Time Frame: 1 year post-CTTI]

Immune Reconstitution Efficacy - Naive CD4 T Cells [Time Frame: 1 year post-CTTI]

Thymus Allograft Biopsy [Time Frame: 2 to 3 months post-CTTI]

Immune Reconstitution Efficacy - Naive CD8 T Cells [Time Frame: 1 year post-CTTI]

Immune Reconstitution Efficacy - Response to Mitogens [Time Frame: 1 year post-CTTI]

Survival at 2 Years Post-CTTI [Time Frame: 2 years post-CTTI]

Immune Reconstitution Efficacy - CD3 T Cells [Time Frame: 1 year post-CTTI]

Secondary ID(s)

932

FDA-FD-R-002606

3R56AI047040-11A1S1

R01AI054843

2R01AI047040-11A2

5K12HD043494-09

Pro00016144

R01AI047040

R56 Bridge R01AI4704011A1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Allergy and Infectious Diseases (NIAID)

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

National Institutes of Health (NIH)

Results

• Results available: Yes
• Date Posted: 17/02/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00576836