Clinical Trial: Thymus Transplantation Safety-Efficacy

Study Status: Available
Recruit Status: Available
Study Type: Expanded Access:   Available for Intermediate-size Population, Treatment IND/Protocol

Official Title: Safety and Efficacy of Thymus Transplantation in Complete DiGeorge Anomaly, IND#9836

Brief Summary:

Complete DiGeorge anomaly (cDGA) is a disorder in which there is no thymus function. With no thymus function, bone marrow stem cells do not develop into T cells, which fight infection. Complete DiGeorge anomaly patients cannot fight infection and are immunodeficient. Without successful treatment, cDGA patients usually die by age 2 years.

Thymus transplantation with and without immunosuppression (drugs given before and after transplantation) has resulted in the development good T cell function in complete DiGeorge anomaly subjects.

This Phase I/II study continues thymus transplantation safety and efficacy research for the treatment of complete DiGeorge anomaly. Eligible participants undergo thymus transplantation and biopsy. Immune function testing is continued for one year post-transplantation.


Detailed Summary:

Complete DiGeorge anomaly (cDGA) is a congenital disorder characterized by athymia. Without successful treatment, children remain immunodeficient and usually die by age 2 years. In complete DiGeorge subjects, thymus transplantation with and without immunosuppression has resulted in diverse T cell development and good T cell function. The purpose of this Phase I/II study is to continue thymus transplantation safety and efficacy research for the treatment of complete DiGeorge anomaly. Until thymus transplantation is FDA approved as standard care for DiGeorge anomaly, research study participation is the only means by which a patient may have access to this potentially life-saving procedure.

This protocol includes 4 groups: one for subjects who do not require immunosuppression; and 3 immunosuppression groups for subjects with different T cell function levels to be suppressed adequately.

Eligible subjects undergo thymus transplantation and an allograft biopsy. Protocol specified studies continue until approximately one year post-transplantation.

Study participation lasts two years.


Sponsor: M. Louise Markert

Current Primary Outcome:

Original Primary Outcome: Survival [ Time Frame: One-year post-transplantation ]

Assess Survival at One Year Post Thymus Transplantation The primary hypothesis is that greater than 50% of subjects will survive thymus transplantation.


Current Secondary Outcome:

Original Secondary Outcome:

  • Descriptive Study - Immune Outcomes [ Time Frame: 6 Months & 1 Year Post-Transplantation ]
    • Total CD3, CD4, CD8, naïve CD8 TCRαβ, TCRγδ, total B cells and total NK cells at 6 months and 12 months post-transplantation.
    • TCR repertoire as assessed by flow cytometry 12 months post-transplantation.
    • PHA response to CD3 and tetanus toxoid at 12 months post-transplantation.
  • Naive CD 4 T Cell Count [ Time Frame: One Year Post-Transplantation ]
    Assess total naïve T cell count at 12 months post-thymus transplantation. The hypothesis is that greater than 50% of subjects will have >100 naïve T cells at one year post-transplantation. An additional hypothesis is that the dose of thymus tissue transplanted will affect the naïve CD4 count at one year.
  • Descriptive Study - GVHD [ Time Frame: 1 Year Post-Transplantation ]
    • Grade of skin GVHD in the first year post-transplantation.
    • Grades of upper & lower intestinal GVHD in the first year post-transplantation.
    • Grade of liver GVHD in the first year post-transplantation.
  • Descriptive Study - Infections [ Time Frame: 1 Year Post-Transplantation ]
    Recording and tabulation of infections during the first 12 months post-transplantation including the organism, infection site, and severity.
  • Descriptive Study - Autoimmune Disease [ Time Frame: 1 Year Post-Transplantation ]
    Autoimmune disease will be recorded and tabulated in first year post-transplantation.
  • Descriptive Study - Persistent Rashes [ Time Frame: 1 Year Post-Transplantation ]
    Description and location of any rashes persisting over 2 weeks will be recorded.
  • Descriptive Study - Thymus Donor T Cell Presence [ Time Frame: 3 Months Post-Transplantation ]
    Tabulate the presence of donor T cells in the blood 3 months post-transplantation.
  • Descriptive Study - Other Adverse Events [ Time Frame: 1 Year Post-Transplantation ]

    Other adverse events possibly, probably and/or definitely transplant-related will be recorded and tabulated.

    • For any cancer, the type of cancer, location and genetic identity.
    • For any granuloma, the location and description.


Information By: Duke University

Dates:
Date Received: September 22, 2010
Date Started: December 2010
Date Completion: December 2023
Last Updated: May 9, 2017
Last Verified: May 2017