Phase 2
N=14
Phase I/II Thymus Transplantation With Immunosuppression #950
DiGeorge Anomaly · Complete DiGeorge Anomaly · Complete Atypical DiGeorge Anomaly · Complete DiGeorge Syndrome · Complete Atypical DiGeorge Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT00579527 ↗Enrolled (actual)
14
Serious AEs
92.9%
Results posted
Feb 2020
Primary outcome: Primary: Survival at 1 Year Post-CTTI — 71 % of participants who survive to 1 year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cultured Thymus Tissue for Implantation (CTTI) (Biological); Cultured Thymus Tissue Implantation and Parental Parathyroid Transplantation (Other); Blood Draw (Procedure); Rabbit anti-thymocyte globulin (Drug); Cyclosporine (Drug); Tacrolimus (Drug); Methylprednisolone or Prednisolone (Drug); Daclizumab (Drug); Mycophenolate mofetil (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Sumitomo Pharma Switzerland GmbH
- Primary completion
- Dec 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Survival at 1 Year Post-CTTI |
71 | — |
| SECONDARY Survival at 2 Years Post-CTTI |
71 | — |
| SECONDARY Immune Reconstitution Efficacy - Total CD3 T Cells |
726 | — |
| SECONDARY Immune Reconstitution Efficacy - Total CD4 T Cells |
593 | — |
| SECONDARY Immune Reconstitution Efficacy - Total CD8 T Cells |
145 | — |
| SECONDARY Immune Reconstitution Efficacy - Naive CD4 T Cells |
156 | — |
| SECONDARY Immune Reconstitution Efficacy - Naive CD8 T Cells |
37 | — |
| SECONDARY Immune Reconstitution Efficacy - Response to Mitogens |
139189 | — |
| SECONDARY Thymus Allograft Biopsy |
7; 0; 3 | — |
Summary
The study purpose is to determine if cultured thymus tissue implantation (CTTI) (previously described as transplantation) with tailored immunosuppression based on the recipient's pre-implantation T cell population is a safe and effective treatment for complete DiGeorge anomaly. This study will also evaluate whether cultured thymus tissue implantation and parathyroid transplantation with immunosuppression is a safe and effective treatment for complete DiGeorge anomaly and hypoparathyroidism.
Eligibility 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/cumm T cells & naive T cell must be 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:
- 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 judgment.
- 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 HSV IgG+.
- 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.
Data sourced from ClinicalTrials.gov (NCT00579527). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.