Serum-Free Thymus Transplantation in DiGeorge Anomaly (SerumFree)
|ClinicalTrials.gov Identifier: NCT00849888|
Recruitment Status : Terminated (The sponsor decided to withdraw the study.)
First Posted : February 24, 2009
Last Update Posted : October 29, 2014
|Condition or disease||Intervention/treatment||Phase|
|DiGeorge Anomaly||Biological: Serum Free Thymus Transplantation with Immunosuppression Other: Serum Free Thymus Transplantation without immunosuppression||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Serum-Free Cultured Thymus Transplantation in DiGeorge Anomaly, IND9836|
|Study Start Date :||April 2008|
|Primary Completion Date :||February 2011|
|Study Completion Date :||February 2011|
Experimental: Atypical Complete DiGeorge
Thymus Transplantation with Immunosuppression
Biological: Serum Free Thymus Transplantation with Immunosuppression
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.
Experimental: Typical Complete DiGeorge
Thymus Transplantation without Immunosuppression
Other: Serum Free Thymus Transplantation without immunosuppression
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.
- Survival [ Time Frame: One year post-thymus transplantation. ]Survival at one year post thymus transplantation.
- Incidence of graft-versus-host-disease (GVHD). [ Time Frame: One year post-thymus-transplantation. ]Development of graft versus host disease in first year after transplantation associated with T cells from the thymus donor.
- Thymopoiesis or graft rejection on biopsy. [ Time Frame: Two months post-thymus transplantation. ]Graft rejection analysis by biopsy at 2 months post-thymus transplantation.
- Incidence of autoimmune disease. [ Time Frame: By two years post-thymus transplantation. ]Incidence of autoimmune disease by year 2 after transplantation Cytopenias as assessed by complete blood counts and differential. Thyroid disease as assessed by thyroid function tests
- Immune outcomes: T cell development; evaluate T cell numbers, diversity, and function. [ Time Frame: One year post-thymus transplantation. ]Number of naïve CD4 T cells at one year after transplantation Number of total CD4 T cells at one year after transplantation Proliferative response to PHA at one year after transplantation TCRBV diversity by spectratyping measured by DKL score at one year after transplantation
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00849888
|Principal Investigator:||M. Louise Markert, M.D., Ph.D||Duke University Medical Center, Pediatrics, Allergy & Immunology|