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Thymus Transplantation in DiGeorge Syndrome #668

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00576407
Recruitment Status : Active, not recruiting
First Posted : December 19, 2007
Last Update Posted : August 28, 2018
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Enzyvant Therapeutics GmbH
Information provided by (Responsible Party):
M. Louise Markert, Duke University

Brief Summary:
The study purpose is to determine whether thymus transplantation without immunosuppression is effective in treating typical complete DiGeorge syndrome.

Condition or disease Intervention/treatment Phase
DiGeorge Syndrome Complete Typical DiGeorge Anomaly Biological: Thymus Tissue for Transplantation Phase 2

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 complete DiGeorge subjects in the operating room. At the time of transplantation, a skin biopsy may have been obtained to look for any preexisting T cells. After transplantation, subjects were followed by routine research immune evaluations, using blood samples obtained approximately 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Thymus Transplantation in Complete DiGeorge Syndrome #668
Study Start Date : November 2001
Actual Primary Completion Date : March 2008
Estimated Study Completion Date : June 2027

Arm Intervention/treatment
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 was 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 approximately 2 years.
Other Names:
  • Thymus Tissue
  • Thymus Tissue Transplantation
  • Thymus Transplant

Primary Outcome Measures :
  1. Survival rate at one year post-transplantation. [ Time Frame: One year post-transplantation. ]

Secondary Outcome Measures :
  1. T cell proliferative response to tetanus toxoid [ Time Frame: Approximately 1 year after transplantation ]
    Proliferative response that is 10 fold over background

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00576407

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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
M. Louise Markert
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Enzyvant Therapeutics GmbH
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Principal Investigator: M. Louise Markert, MD, PhD Duke University Medical Center, Pediatrics, Allergy & Immunology

Publications of Results:
Markert ML and Devlin BH. Thymic reconstitution (in Rich RR, Shearer WT, Fleischer T, Schroeder HW, Weyand CM, Frew A, eds., Clinical Immunology 3rd edn., Elsevier, Edinburgh) p 1253-1262, 2008.
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.

Other Publications:
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Responsible Party: M. Louise Markert, Professor, Duke University Medical Center, Pediatric Allergy & Immunology, Duke University Identifier: NCT00576407     History of Changes
Other Study ID Numbers: Pro00009955
2R01AI047040-11A2 ( U.S. NIH Grant/Contract )
R56 Bridge R01AI4704011A1 ( Other Grant/Funding Number: NIH American Recovery and Reinvestment Act (ARRA) of 2009 )
5K12HD043494-09 ( U.S. NIH Grant/Contract )
R01AI047040 ( U.S. NIH Grant/Contract )
3R56AI047040-11A1S1 ( U.S. NIH Grant/Contract )
R01AI054843 ( U.S. NIH Grant/Contract )
First Posted: December 19, 2007    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M. Louise Markert, Duke University:
Thymus Transplantation
DiGeorge Syndrome
Low T cell numbers
Primary immunodeficiency
DiGeorge Anomaly
Complete DiGeorge
Typical DiGeorge

Additional relevant MeSH terms:
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DiGeorge Syndrome
Marfan Syndrome
Pathologic Processes
22q11 Deletion Syndrome
Craniofacial Abnormalities
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
Parathyroid Diseases
Endocrine System Diseases
Bone Diseases, Developmental
Bone Diseases
Connective Tissue Diseases
Limb Deformities, Congenital