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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Last refreshed on: 12 December 2020
Main ID:  NCT00579527
Date of registration: 20/12/2007
Prospective Registration: No
Primary sponsor: M. Louise Markert
Public title: Phase I/II Thymus Transplantation With Immunosuppression #950 #950
Scientific title: Phase I/II Trial of Thymus Transplantation With Immunosuppression, #950
Date of first enrolment: December 19, 2005
Target sample size: 14
Recruitment status: Completed
Study type:  Interventional
Study design:  Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 1/Phase 2
Countries of recruitment
United States
Name:     M. Louise Markert, MD, PhD
Affiliation:  Duke University Medical Center, Pediatrics, Allergy & Immunology
Key inclusion & exclusion criteria

Thymus Transplantation Inclusion:

- Must have 1 of following: 22q11 or 10p13 hemizygosity; hypocalcemia requiring
replacement; congenital heart defect; CHARGE association or CHD7 mutation; or abnormal
ears plus mother w/diabetes (type I, type II, gestational).

- <50 CD3+ T cells/cumm or <50 CD3+ T cells/cumm that are CD62L+ CD45RA+ (cluster of
differentiation 45RA) (naïve phenotype), or <5% of CD3+ count being CD62L+ CD45RA+

Atypical DiGeorge:

- Must have, or have had, a rash. If rash present, rash biopsy must show T cells in
skin. If rash & adenopathy resolved, must have >50/cumm T cells & naive T cell must be
<50/cumm or <5% of T cells.

Typical DiGeorge:

- CD3+ CD45RA+ CD62L+ T cells <50/mm3 or <5% of total T cells

Parathyroid Transplantation Additional Inclusion:

- 2 studies in recipient which PTH<5 pg/ml when ionized calcium <1.1 mmol/L. Can be done
anytime pre-tx; 1 must be done while at Duke Hospital.

- Parent(s) willing & eligible to be donors

Thymus Transplantation Exclusion:

- Heart surgery <4 wks pre-tx

- Heart surgery anticipated w/in 3 months after proposed tx

- Rejection by surgeon or anesthesiologist as surgical candidate

- Lack of sufficient muscle tissue to accept transplant of 4 grams/m2 BSA

- HIV infection

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

- CMV(>500 copies/ml blood by PCR on 2 tests)

- Ventilator dependence

Parathyroid Donor Inclusion:

- >18 years of age

- Serum calcium in normal range

- Normal PTH function

- HLA typing consistent with parentage

- Not on anticoagulation or can come off

- Parent chosen will share HLA-DR allele with thymus donor that was not inherited by the
recipient. If no HLA matching at all, then either parent is acceptable if the parent
meets other criteria.

Parathyroid Donor Exclusion:

- <18 years old

- Hypoparathyroidism-low PTH in presence of low serum calcium & high serum phosphate

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

- History of cancer

- Donor only living involved parent/guardian of recipient

- Evidence of HIV-1, HIV-2, HTLV-1, HTLV-2, syphilis, hepatitis B, hepatitis C, West
Nile virus, or Chagas disease

- Creutzfeldt Jakob disease (CJD)

- Elevated liver function studies: AST, ALT, alkaline phosphatase >3x upper normal limit

- Receipt of xenograft or risk factors for SARS, CJD and/or smallpox exposure. {If CJD
risk factors but not active disease, parent may give permission for parathyroid use.}

- Urine CMV positive

- Positive CMV IgM

- Positive IgM anti-EBV VCA

- On blood thinners and cannot stop for parathyroid donation

- Elevated PT or PTT (>ULN)

- Platelets<100,000

- Positive Toxoplasma IgM

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

- Hemoglobin <9g/dl

- Infectious head or neck lesion

- Goiter on ultrasound

- Abnormal fiberoptic laryngoscopy of vocal cords

- HLA inconsistent with parentage

- Pregnancy

- Positive HSV IgG isn't exclusion; post-tx prophylaxis needed for recipient if donor is

- Positive VZV IgG isn't exclusion; post-tx prophylaxis needed if donor is VZV IgG+.

- Medical concern of independent otolaryngologist.

- Concern by medical psychologist/social worker that potential donor isn't competent or
does not understand risks.

- Questionnaire responses can lead to exclusion.

Mother of DiGeorge Inclusion:

• Provides consent to use blood/buccal sample. No exclusions except unwillingness to
consent; or, provide blood/buccal sample.

Age minimum: N/A
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Complete Atypical DiGeorge Anomaly
Complete Atypical DiGeorge Syndrome
Complete DiGeorge Anomaly
Complete DiGeorge Syndrome
DiGeorge Anomaly
Biological: Cultured Thymus Tissue for Implantation (CTTI)
Drug: Cyclosporine
Drug: Daclizumab
Drug: Methylprednisolone or Prednisolone
Drug: Mycophenolate mofetil
Drug: Rabbit anti-thymocyte globulin
Drug: Tacrolimus
Other: Cultured Thymus Tissue Implantation and Parental Parathyroid Transplantation
Procedure: Blood Draw
Primary Outcome(s)
Survival at 1 Year Post-CTTI [Time Frame: 1 year post-CTTI]
Secondary Outcome(s)
Immune Reconstitution Efficacy - Naive CD4 T Cells [Time Frame: 1 year 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]
Immune Reconstitution Efficacy - Total CD3 T Cells [Time Frame: 1 year post-CTTI]
Immune Reconstitution Efficacy - Total CD4 T Cells [Time Frame: 1 year post-CTTI]
Immune Reconstitution Efficacy - Total CD8 T Cells [Time Frame: 1 year post-CTTI]
Survival at 2 Years Post-CTTI [Time Frame: 2 years post-CTTI]
Thymus Allograft Biopsy [Time Frame: 2 to 3 months post-CTTI]
Secondary ID(s)
R56 Bridge R01AI4704011A1
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
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)
Ethics review
Results available: Yes
Date Posted: 17/02/2020
Date Completed:
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