Thymus Transplantation With Immunosuppression (884)

March 23, 2022 updated by: Enzyvant Therapeutics GmBH

Thymus Transplantation With Immunosuppression, #884

The research purpose is to determine if thymus transplantation with immunosuppression is a safe and effective treatment for complete DiGeorge anomaly. The research includes studies to evaluate whether thymus transplantation results in complete DiGeorge anomaly subjects developing a normal immune system.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

DiGeorge anomaly is a complex of cardiac defects, parathyroid deficiency, and thymus absence, resulting in profound T-cell deficiency. There is a spectrum of disease in DiGeorge anomaly with respect to all three defects. For complete DiGeorge anomaly subjects with severe T cell defect, the PI had shown that thymus transplantation is safe and efficacious without pretransplantation immunosuppression and with pretransplantation Thymoglobulin and cyclosporine.

Some DiGeorge patients have very poor T cell function and are at risk of death from infection or other immune problems; however, these patients have enough T cell function to reject grafts. This protocol was designed for these patients. Atypical phenotype and some typical phenotype DiGeorge subjects were included in this protocol.

Atypical complete DiGeorge anomaly patients have rash, lymphadenopathy, and oligoclonal T cell proliferations. The T cells have no markers of thymic function (they do not co-express CD45RA and CD62L; they do not contain T cell receptor rearrangement excision circles, TRECs).

Typical complete DiGeorge anomaly patients in this protocol are those whose PHA response >20 fold. Although these patients have very low T cell function, it may be enough to reject a transplant, so Thymoglobulin was used.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Transplant Inclusion

  • No age limit
  • Thyroid studies must be done and if abnormal, must be on therapy

DiGeorge diagnosis - must have 1 symptom from the following list:

  • Heart defect
  • Hypocalcemia requiring replacement
  • 22q11 hemizygosity
  • 10p13 hemizygosity
  • CHARGE association
  • Abnormal ears plus mother with diabetes (type I, type II, or gestational)

Atypical Diagnosis:

  • Must have, or have had, a rash. If rash present, biopsy of rash must show T cells in skin. If rash & adenopathy resolved, must still have oligoclonal T cells.
  • Within 1 month of tx must have PHA response >20 fold above background or >5,000 cpm, whichever is higher, or response can be < this.
  • Circulating CD3+ T cells >50/mm3 but CD45RA+CD62L+CD3+ T cells <50/mm or <5% of CD3 count, whichever is higher (must be done 2x)
  • Immunoscope with >40% oligoclonal TCRBV families. A 2nd test per sponsor discretion if T cell numbers increase or activation status changes.
  • If TREC done pre-tx must have TRECs <100 per 100,000 CD3+ cells.

Typical Diagnosis:

  • Circulating CD3+ CD45RA+ CD62L+ T cells and <50/mm3 or <5% of total T cells
  • PHA response >20 fold above background or >5,000 cpm, whichever is higher.
  • 2 studies must show similar immunological findings qualify for this study.
  • TRECs, if done, should be <100/100,000 CD3 cells

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Thymus Tissue for Transplantation
Biological: Thymus Tissue for Transplantation

3 Thymoglobulin doses given prior to thymus tx. Atypical subjects given Cyclosporine (Csa) pre-tx. Desired Csa concentration 180-300ng/ml. If post-tx T cell count remained <4000/cumm Csa weaned over 8 weeks. If T cell >4,000/cumm, Csa held at 180-300ng/ml.

Thymus tissue, donor, & mother of donor were screened for transplant safety. In operating room, thymic slices were transplanted into quadriceps muscle in 1 or both legs.

Subjects had routine blood research immune evaluations. 2-3 months post-tx, open biopsy of allograft. Immune blood studies continued on surviving subjects until January 2010. Biological Mother: Mother provided blood sample used for DNA extraction, to identify/look for maternal T cell presence in recipient pre-tx, and/or for immune testing post-tx.

Other Names:
  • IND 9836
  • Thymus Tissue Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety & tolerability of Thymoglobulin and cyclosporine followed by thymus transplantation: Survival at 1 year post-transplantation.
Time Frame: 1 year post-transplantation
1 year post-transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Use of additional post transplant immunosuppression after that listed in the protocol.
Time Frame: The post thymus transplantation period
Use of additional post transplant immunosuppression after that listed in the protocol.
The post thymus transplantation period
Allograft biopsy used to evaluate graft rejection
Time Frame: 2 to 4 months post-transplant
Evidence of thymus allograft rejection by immunohistochemistry of biopsy
2 to 4 months post-transplant
CD3 count
Time Frame: 10 - 14 months post-transplantation
CD3 count in cells/mm3
10 - 14 months post-transplantation
Thymopoiesis
Time Frame: 2-4 months after thymus transplantation
Evidence of thymopoiesis in thymus allograft by immunohistochemistry of a biopsy
2-4 months after thymus transplantation
CD4 count
Time Frame: 10-14 months after thymus transplantation
CD4 count in cells/mm3
10-14 months after thymus transplantation
CD8 count
Time Frame: 10-14 months after thymus transplantation
CD8 count in cells/mm3
10-14 months after thymus transplantation
naive CD4 count
Time Frame: 10-14 months after thymus transplantation
naive CD4 count in cells/mm3
10-14 months after thymus transplantation
naive CD8 count
Time Frame: 10-14 months after thymus transplantation
naive CD8 count in cells/mm3
10-14 months after thymus transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Enzyvant Therapeutics GmBH

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: M. Louise Markert, MD, PhD, Duke University Medical Center, Pediatrics, Allergy & Immunology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2002

Primary Completion (Actual)

December 1, 2006

Study Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

December 20, 2007

First Submitted That Met QC Criteria

December 20, 2007

First Posted (Estimate)

December 24, 2007

Study Record Updates

Last Update Posted (Actual)

April 4, 2022

Last Update Submitted That Met QC Criteria

March 23, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00013734
  • R01AI047040 (NIH)
  • R01AI054843 (NIH)
  • 3R56AI047040-11A1S1 (U.S. NIH Grant/Contract)
  • R56 Bridge R01AI4704011A1 (OTHER_GRANT: [NIH American Recovery and Reinvestment Act (ARRA) of 2009])
  • 2R01AI047040-11A2 (NIH)
  • 5K12HD043494-09 (NIH)
  • #884

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on DiGeorge Syndrome

Clinical Trials on Thymus Tissue for Transplantation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Romania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe