NCT00849888

Brief Summary

The study purpose is to determine if thymus tissue cultured in a serum-free (SF) solution is a safe and effective treatment for atypical and typical complete DiGeorge anomaly. \[Funding Source - FDA OOPD\]

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2008

Typical duration for phase_1

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2008

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

February 22, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 24, 2009

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2011

Completed
Last Updated

April 1, 2022

Status Verified

March 1, 2022

Enrollment Period

2.8 years

First QC Date

February 22, 2009

Last Update Submit

March 21, 2022

Conditions

DiGeorge Anomaly

Keywords

Thymus TransplantationDiGeorge AnomalyAthymiaLow T cell numbersImmunoreconstitutionImmunodeficiency

Outcome Measures

Primary Outcomes (3)

  • Survival

    Survival at one year post thymus transplantation.

    One year post-thymus transplantation.

  • Incidence of graft-versus-host-disease (GVHD).

    Development of graft versus host disease in first year after transplantation associated with T cells from the thymus donor.

    One year post-thymus-transplantation.

  • Thymopoiesis or graft rejection on biopsy.

    Graft rejection analysis by biopsy at 2 months post-thymus transplantation.

    Two months post-thymus transplantation.

Secondary Outcomes (2)

  • Incidence of autoimmune disease.

    By two years post-thymus transplantation.

  • Immune outcomes: T cell development; evaluate T cell numbers, diversity, and function.

    One year post-thymus transplantation.

Study Arms (2)

Atypical Complete DiGeorge

EXPERIMENTAL

Thymus Transplantation with Immunosuppression

Biological: Serum Free Thymus Transplantation with Immunosuppression

Typical Complete DiGeorge

EXPERIMENTAL

Thymus Transplantation without Immunosuppression

Other: Serum Free Thymus Transplantation without immunosuppression

Interventions

Serum Free Thymus Transplantation with ImmunosuppressionBIOLOGICAL

Cyclosporine pre-transplant (trough 180-220ng/ml) until naive T cells develop. Subjects \>4,000/cumm T cells, pre-transplant methylprednisolone or prednisolone 1-2mg/kg/day. All subjects pre-transplant days -5,-4,-3: 3 doses 2mg/kg rabbit anti-thymocyte globulin. Thymus tissue (unrelated donor), donor, \& donor's mother screened for safety. Transplant under general anesthesia into quadriceps. First 2 subjects, FBS cultured thymus is transplanted in 1 leg \& serum free (SF) in other. After first 2 subjects \>10% naïve T cells, 3rd receives only SF thymus. After 3rd subject \>10%naive T cells, 4th subject transplanted. Thymus dose 4-18 grams/m2 body surface area. Thymus biopsy 8-12 weeks post-transplant. Skin biopsy at time of transplant \& thymus biopsy. Followed by immune evaluations.

Also known as: IND 9836, Thymus Tissue Transplant
Atypical Complete DiGeorge
Serum Free Thymus Transplantation without immunosuppressionOTHER

Thymus tissue (unrelated donor), donor, \& donor's mother screened for safety. Transplant under general anesthesia into quadriceps. First 2 subjects: FBS cultured thymus transplanted in 1 leg \& serum free cultured thymus in other leg. After first 2 subjects have thymopoiesis in serum-free biopsy, \>10% naïve T cells, 3rd subject receives only serum free cultured thymus. After 3rd subject \>10% naive T cells, 4th subject receives transplant of only serum free cultured thymus. Dose 4-18grams/m2 body surface area. At time of transplant, skin biopsy. Allograft biopsy \& skin biopsy done 8 to 12 weeks post-transplant. (Graft biopsy not done if subject medically unstable.) Post-transplant, subjects followed by immune evaluations, using blood samples, for two years.

Also known as: IND 9836, Thymus Tissue Transplant
Typical Complete DiGeorge

Eligibility Criteria

AgeUp to 2 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Complete DiGeorge anomaly diagnosis
  • Must have one of following:
  • congenital heart disease
  • hypocalcemia requiring replacement
  • q11 or 10p13 hemizygous
  • CHARGE
  • Atypical Arm:
  • Must have, or have had, rash. If rash present, skin biopsy must show T cells. If rash resolved, must have \>50/cumm T cells; \& \<50/cumm naive T cells or \<5% total
  • PHA response must be \<40000 counts per minute(cpm) on immunosuppression; or, \<75000cpm off immunosuppression. PHA test must be done 2x
  • CD45RA+CD62L+ CD3+ T cells must be \<50/mm3; or, \<5% of total CD3. Test must be done 2x
  • Typical Arm:
  • PHA response \<20 fold or \<5,000cpm
  • Circulating CD3+CD45RA+CD62L+T cells \<50/mm3 or \<5% total T cells
  • tests of T cells \& PHA response must show similar results
  • Must be recipient's biological mother

You may not qualify if:

  • Heart surgery \<4 weeks pre-transplant or within 3 months post-transplant
  • Rejection by surgeon or anesthesiologist as surgical candidates
  • Lack of sufficient muscle tissue to accept transplant
  • Medical condition does not allow to undergo a biopsy
  • HIV
  • CMV(\>500 copies/ml blood by PCR on 2 tests)
  • Ventilator dependence
  • GVHD
  • Maternal T cells \>20% of total T cells
  • Prior immune reconstitution attempts (e.g., BMT, prior thymus transplant)
  • Hypoparathyroidism meeting criteria for combined thymus/parathyroid transplant \& parents desiring it
  • RSV or parainfluenza virus
  • Enterovirus or Adenovirus in stool
  • Unwillingness to sign consent or provide blood/buccal samples

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (6)

  • Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007 May 15;109(10):4539-47. doi: 10.1182/blood-2006-10-048652. Epub 2007 Feb 6.

    PMID: 17284531BACKGROUND

  • Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, Sedlak DA, Sempowski GD, Hale LP, Rice HE, Mahaffey SM, Skinner MA. Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood. 2004 Oct 15;104(8):2574-81. doi: 10.1182/blood-2003-08-2984. Epub 2004 Apr 20.

    PMID: 15100156BACKGROUND

  • Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, Le Deist F, Alexieff MJ, Li J, Hauser ER, Haynes BF, Rice HE, Skinner MA, Mahaffey SM, Jaggers J, Stein LD, Mill MR. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003 Aug 1;102(3):1121-30. doi: 10.1182/blood-2002-08-2545. Epub 2003 Apr 17.

    PMID: 12702512BACKGROUND

  • Selim MA, Markert ML, Burchette JL, Herman CM, Turner JW. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study. J Cutan Pathol. 2008 Apr;35(4):380-5. doi: 10.1111/j.1600-0560.2007.00816.x.

    PMID: 18333898BACKGROUND

  • Chinn IK, Devlin BH, Li YJ, Markert ML. Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol. 2008 Mar;126(3):277-81. doi: 10.1016/j.clim.2007.11.009. Epub 2007 Dec 26.

    PMID: 18155964BACKGROUND

  • Markert ML, Li J, Devlin BH, Hoehner JC, Rice HE, Skinner MA, Li YJ, Hale LP. Use of allograft biopsies to assess thymopoiesis after thymus transplantation. J Immunol. 2008 May 1;180(9):6354-64. doi: 10.4049/jimmunol.180.9.6354.

    PMID: 18424759BACKGROUND

MeSH Terms

Conditions

DiGeorge SyndromeThymic aplasiaImmunologic Deficiency Syndromes

Interventions

Immunosuppression Therapy

Condition Hierarchy (Ancestors)

22q11 Deletion SyndromeCraniofacial AbnormalitiesMusculoskeletal AbnormalitiesMusculoskeletal DiseasesHeart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesLymphatic AbnormalitiesLymphatic DiseasesHemic and Lymphatic DiseasesAbnormalities, MultipleCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesChromosome DisordersGenetic Diseases, InbornHypoparathyroidismParathyroid DiseasesEndocrine System DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

ImmunotherapyImmunomodulationBiological TherapyTherapeuticsImmunologic TechniquesInvestigative Techniques

Study Officials

  • M. Louise Markert, M.D., Ph.D

    Duke University Medical Center, Pediatrics, Allergy & Immunology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 22, 2009

First Posted

February 24, 2009

Study Start

April 1, 2008

Primary Completion

February 1, 2011

Study Completion

February 1, 2011

Last Updated

April 1, 2022

Record last verified: 2022-03