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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.
ClinicalTrials.gov Identifier: NCT00576407
Recruitment Status : Active, not recruiting
First Posted : December 19, 2007
Last Update Posted : August 28, 2018
Sponsor:
Collaborators:
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

Tracking Information
First Submitted Date  ICMJE December 17, 2007
First Posted Date  ICMJE December 19, 2007
Last Update Posted Date August 28, 2018
Study Start Date  ICMJE November 2001
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2012)
Survival rate at one year post-transplantation. [ Time Frame: One year post-transplantation. ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2007)
Survival rate at one year post-transplantation. T cell reconstitution: proliferative response to Tetanus Toxoid of greater than ten-fold. [ Time Frame: One year post-transplantation. ]
Change History Complete list of historical versions of study NCT00576407 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2012)
T cell proliferative response to tetanus toxoid [ Time Frame: Approximately 1 year after transplantation ]
Proliferative response that is 10 fold over background
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2007)
T cell responses to mitogens and T cell numbers [ Time Frame: Ongoing ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Thymus Transplantation in DiGeorge Syndrome #668
Official Title  ICMJE Phase II Study of Thymus Transplantation in Complete DiGeorge Syndrome #668
Brief Summary The study purpose is to determine whether thymus transplantation without immunosuppression is effective in treating typical complete DiGeorge syndrome.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • DiGeorge Syndrome
  • Complete Typical DiGeorge Anomaly
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: 1
Thymus Tissue for Transplantation in Complete DiGeorge Syndrome
Intervention: Biological: Thymus Tissue for Transplantation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 28, 2011)
26
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2007)
40
Estimated Study Completion Date  ICMJE June 2027
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00576407
Other Study ID Numbers  ICMJE 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 )
#668
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M. Louise Markert, Duke University
Study Sponsor  ICMJE M. Louise Markert
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Principal Investigator: M. Louise Markert, MD, PhD Duke University Medical Center, Pediatrics, Allergy & Immunology
PRS Account Duke University
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP