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Thymus Transplantation Safety-Efficacy

Expanded access is currently available for this treatment.
Verified May 2017 by M. Louise Markert, Duke University Medical Center
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 Medical Center
ClinicalTrials.gov Identifier:
NCT01220531
First received: September 22, 2010
Last updated: May 9, 2017
Last verified: May 2017
September 22, 2010
May 9, 2017
December 2010
December 2021   (Final data collection date for primary outcome measure)
Not Provided
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.
Complete list of historical versions of study NCT01220531 on ClinicalTrials.gov Archive Site
Not Provided
  • 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.
Not Provided
Not Provided
 
Thymus Transplantation Safety-Efficacy
Safety and Efficacy of Thymus Transplantation in Complete DiGeorge Anomaly, IND#9836

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.

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.

Expanded Access:   Available for Intermediate-size Population, Treatment IND/Protocol
Not Provided
Not Provided
  • Complete DiGeorge Anomaly
  • DiGeorge Syndrome
  • DiGeorge Anomaly
  • Complete DiGeorge Syndrome
  • Biological: Thymus Tissue for Transplantation
    Potential thymus recipient subjects are screened for eligibility. Thymus tissue (unrelated donor), donor, & donor's mother screened for safety. Thymus transplantation is done under general anesthesia in the operating room. Thymus tissue is transplanted into the subject's quadriceps. Two to three months post-transplantation, if medically stable, the subject undergoes allograft biopsy. At the time of transplantation and biopsy, skin biopsy conducted. Subjects undergo laboratory testing for approximately one year post-transplantation. At year 2 post-transplantation, subjects are contacted for data collection.
    Other Name: Thymus Tissue Transplant
  • Procedure: Blood Draw
    Biological Mothers of Thymus Recipients are asked to participate in the study and undergo phlebotomy to allow for testing of T cell identity in the complete DiGeorge subjects. If blood is not obtainable, then a buccal swab may be done.
    Other Name: Venipuncture
  • Drug: Rabbit anti-thymocyte globulin
    Three doses of 2 mg/kg IV prior to thymus transplantation. Each dose is given over 12 hours. RATGAM is usually given on days -5, -4, and -3 prior to thymus transplantation.
    Other Name: RATGAM
  • Drug: Cyclosporine
    Csa may be given every 8 to 12 hours orally or IV before and after thymus transplantation. The Csa dose is dependent on T cell numbers and the target CSA trough levels. Csa is weaned as per protocol.
    Other Name: Csa
  • Drug: Tacrolimus
    If unable to tolerate cyclosporine, then FK506 is given. FK506 may be given every 8 to 12 hours orally or IV before and after thymus transplantation. FK506 dose is dependent on T cell numbers and the target FK506 trough levels. FK506 is weaned as per protocol.
    Other Name: FK506
  • Drug: Methylprednisolone or Prednisolone
    Steroids IV or orally may be given before and/or after thymus transplantation. Administration and dosage depends on T cell numbers. Steroids are weaned as per protocol.
    Other Name: Steroids
  • Drug: Basiliximab
    A single dose of Basiliximab 5 mg/kg IV may be given. Administration of Basiliximab depends on T cell numbers and T cell activation. A single dose of Basiliximab may be given after the administration of rabbit anti-thymocyte globulin and before thymus transplantation. If Basiliximab is not given before thymus transplantation, and, depending on the T cell numbers and T cell activation, a single dose of Basiliximab may be given 3 to 5 days after thymus transplantation.
    Other Name: Simulect
  • Drug: Mycophenolate mofetil
    Mycophenolate mofetil may be given if the T cell count remains elevated 5 days after thymus transplantation. If MMF is given, the dose is 15 mg/kg/dose every 8 hours IV or orally. MMF may be stopped at 35 days or continued for up to six months after thymus transplantation.
    Other Names:
    • MMF
    • CellCept
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Available
Not Provided
December 2023
December 2021   (Final data collection date for primary outcome measure)

Transplant Inclusion:

  • Must have 1 of following: 22q11 or 10p13 hemizygosity; hypocalcemia requiring replacement; congenital heart disease; CHARGE association or CHD7 mutation
  • Complete DiGeorge: <50 CD3+ T cells/cumm or <50 CD3+ T cells/cumm that are CD62L+ CD45RA+, or <5% of CD3+ cells are CD62L+ CD45RA+
  • Atypical DiGeorge must have, or have had, a rash.

Group 1

•Typical cDGA whose T cells have a PHA response < 5,000 cpm and < 20 fold PHA response.

Group 2

•Typical cDGA whose T cells have a PHA response >5,000 cpm and <50,000 cpm and >20 fold PHA response

Group 3

  • Typical cDGA whose T cells have PHA response >50,000 cpm
  • Typical cDGA with maternal engraftment
  • Atypical cDGA whose T cells have PHA response <40,000 cpm when on immunosuppression or <75,000 cpm to PHA when not on immunosuppression
  • Atypical cDGA with group 3 PHA response & maternal engraftment

Group 4

  • Atypical cDGA with PHA responses >75,000cpm while on no immunosuppression or PHA responses >40,000cpm while on immunosuppression
  • Atypical cDGA with maternal engraftment and group 4 PHA response

Transplant Exclusion:

  • Heart surgery <4 wks pre-transplantation
  • Heart surgery anticipated w/in 3 months after proposed transplantation
  • Rejection by surgeon or anesthesiologist as surgical candidate
  • Lack of sufficient muscle tissue to accept transplant of 4 grams/m2 body surface area
  • HIV infection
  • Prior attempts at immune reconstitution, such as bone marrow transplant or previous thymus transplant
  • CMV on 2 tests for Groups 2, 3, and 4

Biological Mother Inclusion/Exclusion:

• Must be biological mother of thymus recipient

Sexes Eligible for Study: All
Child, Adult, Senior
No
Contact: M. Louise Markert, M.D., Ph.D 919-684-6263 marke001@mc.duke.edu
Contact: Stephanie Gupton, RN, CPNP 919-684-4704 stephanie.gupton@dm.duke.edu
United States
 
 
NCT01220531
Pro00025966
2R01AI047040-11A2 ( U.S. NIH Grant/Contract )
5K12HD043494-09 ( U.S. NIH Grant/Contract )
Not Provided
Not Provided
Not Provided
M. Louise Markert, Duke University Medical Center
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
Principal Investigator: M. Louise Markert, M.D., Ph.D Duke University Medical Center, Pediatrics, Allergy & Immunology
Duke University
May 2017

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