Gene Therapy for ADA-SCID

Study Overview
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Brief Summary
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This study investigated the safety and efficacy of different gene therapy approaches for Severe Combined Immunodeficiency (SCID) caused by the deficiency of adenosine deaminase (ADA) enzyme. This is a severe condition that can be cured by HLA-matched sibling donor bone marrow transplantation. Patients were enrolled if no HLA-identical sibling donor was available and the patient showed evidence of failure of enzyme replacement therapy or this treatment was not a long-term available option. The aim of the study was to evaluate the safety and efficacy of the procedure and to identify the relative role of peripheral blood lymphocytes and hematopoietic stem cells and progenitor cells in the long-term reconstitution of immune functions after retroviral vector mediated ADA gene transfer.

Detailed Description
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This is mono-centric, non-randomized, non-controlled, open label, phase I-II trial that evaluated the safety and efficacy of ADA gene transfer into somatic cells for the treatment of ADA-SCID

Official Title
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Treatment of ADA-SCID by Gene Therapy on Somatic Cells

Conditions
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Severe Combined Immunodeficiency Syndrome

Intervention / Treatment
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* Genetic: gene transduced PBL and/or gene transduced HSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lack of HLA-identical sibling donor and Evidence of failure of the enzyme replacement treatment after >6 months or PEG-ADA is not available as a life long option Exclusion Criteria: HLA identical bone marrow sibling donor HIV infection Malignancy
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PBL/HSC<br> | Genetic: gene transduced PBL and/or gene transduced HSC<br>* infusions of autologous PBL and/or HSC transduced with retroviral vectors encoding ADA<br>* Other names: gene therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety of the administration of the autologous PBL and/or autologous HSC transduced with the normal human ADA gene |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of extent, kinetic and duration of the engraftment of transduced cells and the potential selective advantage of ADA positive cells |  |  | 
| Evaluation of efficacy of the administration of autologous PBL/HSC(Clinical, immunological, hematological, microbiological, ADA activity and purine metabolism) |  |  | 
| To identify the relative role of peripheral blood lymphocytes and hematopoietic stem cells and progenitor cells in the long-term reconstitution of immune functions after gene therapy |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCID, adenosine deaminase, gene therapy, retroviral vector