Phase 2
N=26
Thymus Transplantation in DiGeorge Syndrome #668
DiGeorge Syndrome · Complete Typical DiGeorge Anomaly
Bottom Line
View on ClinicalTrials.gov: NCT00576407 ↗Enrolled (actual)
26
Serious AEs
88.5%
Results posted
Feb 2020
Primary outcome: Primary: Survival at 1 Year Post-Cultured Thymus Tissue Implantation (CTTI) — 72 % of participants who survive to 1 year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cultured Thymus Tissue for Implantation (CTTI) (Biological)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Sumitomo Pharma Switzerland GmbH
- Primary completion
- Apr 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Survival at 1 Year Post-Cultured Thymus Tissue Implantation (CTTI) |
72 | — |
| SECONDARY Survival at 2 Years Post-CTTI |
72 | — |
| SECONDARY Immune Reconstitution Efficacy - Total CD3 T Cells |
770 | — |
| SECONDARY Immune Reconstitution Efficacy - Total CD4 T Cells |
570 | — |
| SECONDARY Immune Reconstitution Efficacy - Total CD8 T Cells |
122 | — |
| SECONDARY Immune Reconstitution Efficacy - Naive CD4 T Cells |
270 | — |
| SECONDARY Immune Reconstitution Efficacy - Naive CD8 T Cells |
65 | — |
| SECONDARY Immune Reconstitution Efficacy - Response to Mitogens |
133000 | — |
| SECONDARY Thymus Allograft Biopsy |
17; 1; 1 | — |
Summary
The study purpose is to determine whether cultured thymus tissue implantation (CTTI) is effective in treating typical complete DiGeorge syndrome.
Eligibility Criteria
Inclusion Criteria
- The subject's parent(s) signed the ICF.
- For a diagnosis of DiGeorge Syndrome (DGS), the subject had one of the following:
- Heart defect
- Hypoparathyroidism
- 22q11 hemizygosity
- 10p13 hemizygosity
- Coloboma, heart defect, choanal atresia, growth and development retardation, genital hypoplasia, ear anomalies/ deafness CHARGE association mutation (CHD7 deletion);
- PHA proliferative responses less than 20-fold above background.
- Subjects with typical Complete DiGeorge Anomaly (cDGA) had to have one of the following on 2 separate occasions:
- Circulating CD3+ T cells by flow cytometry 50/mm3, then CD45RA+ (cluster of differentiation 45RA) CD62L+ had to be 500/mm3 and CD45RA+ CD62L+ CD3+ T cells 500/mm3 and CD45RA+ CD62L+ CD3+ T cells < 50/mm3 and TRECs less than 100 per 100,000 CD3+ cells.
- T cell proliferative response to PHA more than 20-fold over background. While T cell response to PHA might have been seen, eligible subjects were to have no T cell proliferative response to antigens (less than 20-fold response) and were to have serious clinical problems related to immunodeficiency, such as opportunistic infection or failure to thrive.
Exclusion Criteria
- Subjects on ventilators, with tracheostomies, with cytomegalovirus (CMV) infections, or requiring ongoing steroids could still be enrolled, but their data were to be analyzed separately
- Subjects who had heart surgery < 4 weeks prior to transplant
- Heart surgery anticipated within 3 months of the proposed time of transplantation
- Ongoing parenteral steroid therapy between enrollment and transplantation
- Present or past lymphadenopathy
- Rash associated with T cell infiltration of the dermis and epidermis
- Rejection by the surgeon or anesthesiologist as surgical candidates
- Lack of sufficient muscle tissue to accept a transplant of 4 g/m2 body surface area (BSA) of the recipient
- Prior attempts at immune reconstitution, such as bone marrow transplantation or previous thymus transplantation
- Human immunodeficiency virus (HIV) infection
Data sourced from ClinicalTrials.gov (NCT00576407). 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.