Thymus Transplantation in DiGeorge Syndrome #668

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
M. Louise Markert, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00576407
First received: December 17, 2007
Last updated: August 21, 2014
Last verified: August 2014
  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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Survival rate at one year post-transplantation. [ Time Frame: One year post-transplantation. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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:
  • Thymus Tissue
  • Thymus Tissue Transplantation
  • Thymus Transplant

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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576407

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
M. Louise Markert
Investigators
Principal Investigator: M. Louise Markert, MD, PhD Duke University Medical Center, Pediatrics, Allergy & Immunology
  More Information

Publications:
Markert ML, Devlin BH, McCarthy EA, Chinn IK, Hale LP. Thymus Transplantation in Thymus Gland Pathology: Clinical, Diagnostic, and Therapeutic Features. Eds Lavinin C, Moran CA, Morandi U, Schoenhuber R. Springer-Verlag Italia, Milan, 2008, pp 255-267.

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, 2R01AI047040-11A2, R56 Bridge R01AI4704011A1, 5K12HD043494-09, R01AI047040, 3R56AI047040-11A1S1, R01AI054843, #668
Study First Received: December 17, 2007
Last Updated: August 21, 2014
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:
Craniofacial Abnormalities
Syndrome
DiGeorge Syndrome
Disease
Pathologic Processes
22q11 Deletion Syndrome
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Lymphatic Abnormalities
Lymphatic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Hypoparathyroidism
Parathyroid Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 18, 2014