Phase I/II Thymus Transplantation With Immunosuppression #950

Phase 1

Completed

• Conditions: Complete Atypical DiGeorge Syndrome; DiGeorge Anomaly; Complete Atypical DiGeorge Anomaly; Complete DiGeorge Syndrome; Complete DiGeorge Anomaly
• Interventions: Biological: Cultured Thymus Tissue for Implantation (CTTI); Other: Cultured Thymus Tissue Implantation and Parental Parathyroid Transplantation; Procedure: Blood Draw; Drug: Rabbit anti-thymocyte globulin; Drug: Cyclosporine; Drug: Tacrolimus; Drug: Methylprednisolone or Prednisolone; Drug: Daclizumab; Drug: Mycophenolate mofetil

• Registration Number: NCT00579527
• Lead Sponsor: Sumitomo Pharma Switzerland GmbH

Brief Summary

The study purpose is to determine if cultured thymus tissue implantation (CTTI) (previously described as transplantation) with tailored immunosuppression based on the recipient's pre-implantation T cell population is a safe and effective treatment for complete DiGeorge anomaly. This study will also evaluate whether cultured thymus tissue implantation and parathyroid transplantation with immunosuppression is a safe and effective treatment for complete DiGeorge anomaly and hypoparathyroidism.

Detailed Description

Complete DiGeorge anomaly is a congenital disorder characterized by athymia. Without successful treatment, children remain immunodeficient and usually die by age 2 years. In infants with complete DiGeorge anomaly and no T cells, cultured thymus tissue implantation (CTTI) without immunosuppression resulted in diverse T cell development and good T cell function. Some infants with no thymus have some T cells that presumably developed extrathymically; these T cells can reject a thymus graft.

The purpose of this study is to tailor immunosuppression use for complete DiGeorge anomaly subjects who have some T cells and different T cell function levels. This protocol includes tailored immunosuppression regimens to allow subjects with different T cell function levels to be suppressed adequately.

Patients with complete DiGeorge often have hypoparathyroidism, a life threatening condition. Successful CTTI does not result in improvement of the hypoparathyroidism. The patients must go to the clinic for frequent calcium levels and to the hospital for calcium infusions. These infants are at risk for seizures from low calcium. This study had a parental parathyroid transplant arm for subjects with hypoparathyroidism who require calcium replacement.

Whether or not a subject was enrolled in the parathyroid arm, the immunosuppression regimen the subject received was dependent on the immune findings as stated in the clinical protocol.

Study Timeline

• Study Start: 2005-12-19
• Study First Submitted: 2007-12-20
• Study First Submitted QC: 2007-12-20
• Study First Posted: 2007-12-24
• Primary Completion: 2011-12
• Disposition First Submitted: 2015-12-10
• Disposition First Submitted QC: 2015-12-10
• Disposition First Posted: 2016-01-12
• Study Completion: 2017-12-31
• Results First Submitted: 2019-12-27
• Results First Submitted QC: 2020-02-04
• Results First Posted: 2020-02-17
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-23
• Last Update Posted: 2022-03-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression	Methylprednisolone or Prednisolone	Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression	Cultured Thymus Tissue for Implantation (CTTI)	Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
CTTI with Parathyroid Transplantation w/immunosuppression	Blood Draw	Patients with complete DiGeorge Anomaly (cDGA) undergoes cultured thymus tissue thymus implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function. If the patient has hypoparathyroidism, and is eligible, the patient may also receive a parathyroid transplant.
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression	Blood Draw	Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression	Rabbit anti-thymocyte globulin	Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
CTTI with Parathyroid Transplantation w/immunosuppression	Cultured Thymus Tissue Implantation and Parental Parathyroid Transplantation	Patients with complete DiGeorge Anomaly (cDGA) undergoes cultured thymus tissue thymus implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function. If the patient has hypoparathyroidism, and is eligible, the patient may also receive a parathyroid transplant.
CTTI with Parathyroid Transplantation w/immunosuppression	Rabbit anti-thymocyte globulin	Patients with complete DiGeorge Anomaly (cDGA) undergoes cultured thymus tissue thymus implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function. If the patient has hypoparathyroidism, and is eligible, the patient may also receive a parathyroid transplant.
CTTI with Parathyroid Transplantation w/immunosuppression	Methylprednisolone or Prednisolone	Patients with complete DiGeorge Anomaly (cDGA) undergoes cultured thymus tissue thymus implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function. If the patient has hypoparathyroidism, and is eligible, the patient may also receive a parathyroid transplant.
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression	Cyclosporine	Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression	Tacrolimus	Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression	Mycophenolate mofetil	Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression	Daclizumab	Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
CTTI with Parathyroid Transplantation w/immunosuppression	Cyclosporine	Patients with complete DiGeorge Anomaly (cDGA) undergoes cultured thymus tissue thymus implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function. If the patient has hypoparathyroidism, and is eligible, the patient may also receive a parathyroid transplant.
CTTI with Parathyroid Transplantation w/immunosuppression	Tacrolimus	Patients with complete DiGeorge Anomaly (cDGA) undergoes cultured thymus tissue thymus implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function. If the patient has hypoparathyroidism, and is eligible, the patient may also receive a parathyroid transplant.

Primary Outcome Measures

Name	Time	Method
Survival at 1 Year Post-CTTI	1 year post-CTTI	Survival at 1 year post cultured thymus tissue implantation was assessed using the Kaplan Meier Estimated Survival. This mathematical function estimates the survival for a certain length of time.

Secondary Outcome Measures

Name	Time	Method
Immune Reconstitution Efficacy - Total CD3 T Cells	1 year post-CTTI	The development of total CD3 T cells at one year as measured using flow cytometry
Immune Reconstitution Efficacy - Naive CD8 T Cells	1 year post-CTTI	The development of total naive CD8 T cells at one year as measured using flow cytometry
Immune Reconstitution Efficacy - Total CD8 T Cells	1 year post-CTTI	The development of total CD8 T cells at one year as measured using flow cytometry
Immune Reconstitution Efficacy - Naive CD4 T Cells	1 year post-CTTI	The development of total naive CD4 T cells at one year as measured using flow cytometry
Immune Reconstitution Efficacy - Response to Mitogens	1 year post-CTTI	Measurement of the T cell proliferative response to the mitogen phytohemagglutin (PHA).
Survival at 2 Years Post-CTTI	2 years post-CTTI	Survival at 2 years post cultured thymus tissue implantation was assessed using the Kaplan Meier Estimated Survival. This mathematical function estimates the survival for a certain length of time.
Immune Reconstitution Efficacy - Total CD4 T Cells	1 year post-CTTI	The development of total CD4 T cells at one year as measured using flow cytometry
Thymus Allograft Biopsy	2 to 3 months post-CTTI	Evidence, on biopsy of the thymus tissue implanted in muscle, that shows the development of new T cells.

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States