Thymus Transplantation in DiGeorge Syndrome #668
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Purpose
The study purpose is to determine whether thymus transplantation without immunosuppression is effective in treating typical complete DiGeorge syndrome.
| Condition | Intervention | Phase |
|---|---|---|
|
DiGeorge Syndrome Complete Typical DiGeorge Anomaly |
Biological: Thymus Tissue for Transplantation |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase II Study of Thymus Transplantation in Complete DiGeorge Syndrome #668 |
- Survival rate at one year post-transplantation. [ Time Frame: One year post-transplantation. ] [ Designated as safety issue: Yes ]
- T cell proliferative response to tetanus toxoid [ Time Frame: Approximately 1 year after transplantation ] [ Designated as safety issue: No ]Proliferative response that is 10 fold over background
| Enrollment: | 26 |
| Study Start Date: | November 2001 |
| Estimated Study Completion Date: | June 2027 |
| Primary Completion Date: | February 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Thymus Tissue for Transplantation in Complete DiGeorge Syndrome
|
Biological: Thymus Tissue for Transplantation
Thymus transplantation is done using allogeneic cultured postnatal tissue from unrelated donors. Thymus tissue, the donor, & donor's mother were screened for safety. Approximately 2-3 weeks post-harvest thymus slices were transplanted into the recipient's quadriceps. Dose is number of grams of transplanted tissue divided by the recipient's weight in kilograms. Minimum dose was 4 g/m2. Maximum dose 18g/m2. At time of transplantation, a skin biopsy was obtained to look for preexisting T cells. 2-3 months post-transplant allograft biopsy to evaluate for thymopoiesis & graft rejection. At time of biopsy, skin biopsy done to look for T cell clonal populations. Post-transplant, subjects followed by routine research immune evaluations, using blood samples for 2 years.
Other Names:
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Detailed Description:
There is no safe and effective treatment for DiGeorge syndrome and most patients die by the age of two. Complete DiGeorge syndrome is characterized by very low T cell or very low naïve T cell numbers. In this study, typical complete DiGeorge syndrome subjects received human postnatal cultured thymus tissue transplants. Thymus tissue that would otherwise be discarded was transplanted into DiGeorge subjects in the operating room. At the time of transplantation, a skin biopsy was obtained to look for any preexisting T cells. After transplantation, subjects were followed by routine research immune evaluations, using blood samples obtained every 2-4 weeks. At approximately 2-3 months post-transplantation subjects underwent an open biopsy of the allograft. The biopsy was done under general anesthesia in the operating room. At the time of the graft biopsy, another skin biopsy was obtained to look for clonal populations of T cells.
The protocol aims include: assessing thymopoiesis in the allograft biopsy; assessing immunoreconstitution of complete DiGeorge syndrome subjects after postnatal allogeneic thymus transplantation; assessing minimally invasive methods of assessing thymopoiesis (flow cytometry and polymerase chain reaction (PCR); assessing pre-transplant T cells which do not proliferate in response to mitogens (focusing on NK-T cells); and, assessing thymus transplantation safety and toxicity.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of complete DiGeorge syndrome which is either: T cells with < 50/mm3 with naive phenotype; or < 5% CD3 + T cells with naive T cell phenotype.
- Diagnosis of typical DiGeorge syndrome phenotype: < 50 T cells/cumm and very low proliferative responses to mitogens (e.g. < 20 fold response to mitogen phytohemagglutinin).
- Proliferative response to PHA < 20 fold above background or < 5000 counts per minute(cpm), whichever is higher.
{Note: Subjects with PHA responses 20 fold or more over background or > 5,000 cpm, whichever is higher, may be enrolled in another thymus transplant protocol.}
- Must have heart disease; hypocalcemia requiring replacement; 22q11 or 10p13 hemizygosity; CHARGE association; or must be child of diabetic mother and have abnormal ears.
Exclusion Criteria:
- Those who do not meet inclusion criteria
- Atypical DiGeorge syndrome phenotype
- Rash indicating atypical DiGeorge syndrome phenotype.
Transplant Exclusion:
- Heart surgery <4 weeks pre-tx date
- Heart surgery anticipated w/in 3 months of proposed tx
- Rejection by surgeon or anesthesiologist as surgical candidates
- Lack of sufficient muscle tissue to accept 0.2 grams/kg transplant
Contacts and Locations| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| Principal Investigator: | M. Louise Markert, MD, PhD | Duke University Medical Center, Pediatrics, Allergy & Immunology |
More Information
Publications:
| Responsible Party: | M. Louise Markert, Associate Professor, Duke University Medical Center, Pediatric Allergy & Immunology, Duke University Medical Center |
| ClinicalTrials.gov Identifier: | NCT00576407 History of Changes |
| Other Study ID Numbers: | Pro00009955 #668, 2R01AI047040-11A2, R56 Bridge R01AI4704011A1, 5K12HD043494-09, R01AI047040, 3R56AI047040-11A1S1, R01AI054843 |
| Study First Received: | December 17, 2007 |
| Last Updated: | February 12, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by Duke University:
|
Thymus Transplantation DiGeorge Syndrome Athymia Low T cell numbers Immunoreconstitution |
Primary immunodeficiency DiGeorge Anomaly Complete DiGeorge Typical DiGeorge |
Additional relevant MeSH terms:
|
Congenital Abnormalities DiGeorge Syndrome 22q11 Deletion Syndrome Craniofacial Abnormalities Musculoskeletal Abnormalities Musculoskeletal Diseases Heart Defects, Congenital Cardiovascular Abnormalities Cardiovascular Diseases |
Heart Diseases Lymphatic Abnormalities Lymphatic Diseases Abnormalities, Multiple Chromosome Disorders Genetic Diseases, Inborn Hypoparathyroidism Parathyroid Diseases Endocrine System Diseases |
ClinicalTrials.gov processed this record on May 16, 2013