Serum-Free Thymus Transplantation in DiGeorge Anomaly

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-30

Study Completion Date

2011-02-28

Brief Summary

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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. \[Funding Source - FDA OOPD\]

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Detailed Description

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Complete DiGeorge anomaly is a congenital disorder characterized by athymia. Without successful treatment, patients remain immunodeficient and usually die by age 2 years. In "typical" complete DiGeorge subjects who have no T cells, thymus transplantation without immunosuppression has resulted in diverse T cell development and good T cell function. In "atypical" complete DiGeorge subjects who have no thymus, a rash, and some T cells that presumably developed extrathymically, thymus transplantation with immunosuppression has resulted in diverse T cell development and good T cell function. Thus far, thymus transplantation studies have used thymus cultured in fetal bovine serum (FBS medium). This protocol's purpose is to determine whether transplanted thymus cultured in serum free medium can safely support thymopoiesis and T cell reconstitution as does FBS medium cultured thymus tissue in DiGeorge anomaly subjects. This protocol includes 2 arms: atypical DiGeorge subjects who will receive immunosuppression and thymus transplantation; and, typical complete DiGeorge subjects who will receive thymus transplantation without immunosuppression. Serum free medium use would reduce concerns of animal product exposure including potential exposure to bovine spongiform encephalopathy(BSE).

Conditions

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DiGeorge Anomaly

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Atypical Complete DiGeorge

Thymus Transplantation with Immunosuppression

Group Type EXPERIMENTAL

Serum Free Thymus Transplantation with Immunosuppression

Intervention Type BIOLOGICAL

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.

Typical Complete DiGeorge

Thymus Transplantation without Immunosuppression

Group Type EXPERIMENTAL

Serum Free Thymus Transplantation without immunosuppression

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type BIOLOGICAL

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.

Intervention Type OTHER

Other Intervention Names

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IND 9836 Thymus Tissue Transplant IND 9836 Thymus Tissue Transplant

Eligibility Criteria

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Inclusion Criteria

Complete DiGeorge anomaly diagnosis

Must have one of following:

* congenital heart disease
* hypocalcemia requiring replacement
* 22q11 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
* 2 tests of T cells \& PHA response must show similar results

Biological Mother Inclusion:

-Must be recipient's biological mother

Thymus Recipient Exclusion:

* 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

Biological Mother Exclusion:

-Unwillingness to sign consent or provide blood/buccal samples

Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No