Methodology Study of Retroviral Insertion Site Analysis in Strimvelis Gene Therapy

Study Overview
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Brief Summary
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To evaluate accuracy and precision of retroviral insertion site (RIS) analysis and its utility for investigating and predicting the potential for insertional oncogenesis in subjects treated with Strimvelis.

Detailed Description
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To evaluate accuracy and precision of shearing extension primer tag selection ligation-mediated polymerase chain reaction (S-EPTS/LM-PCR) retroviral insertion site (RIS) analysis and its utility for investigating and predicting the potential for insertional oncogenesis in subjects previously treated with Strimvelis for severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency.

Official Title
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Methodology Study to Investigate the Utility of Retroviral Insertion Site Analysis in Samples From Subjects Treated With Strimvelis Gene Therapy

Conditions
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Severe Combined Immunodeficiency Due to ADA Deficiency

Intervention / Treatment
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* Other: Retroviral Insertion Site Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects must have received gRV-GT as part of a clinical trial, expanded access program, as an approved product (Strimvelis) or under a post-approval hospital exemption, and must have at least one retained biological sample that meets the following eligibility criteria: Peripheral blood, bone marrow, or DNA extracted from either source. Taken at least 6 months after gRV-GT. Stored at -20oC or below since the time of sampling. Likely to provide at least 1.5 μg of DNA (following extraction by the central laboratory). There is no restriction on the number of samples from a single subject, or on the time that has elapsed since sampling. Exclusion Criteria N/A
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subjects Previously Treated with Strimvelis Gene Therapy<br>It is expected that this study will include approximately 70 eligible samples from approximately 15 subjects previously treated with gamma retroviral gene therapy (gRV-GT). | Other: Retroviral Insertion Site Analysis<br>* Shearing extension primer tag selection ligation-mediated polymerase chain reaction (S-EPTS/LM-PCR) retroviral insertion site (RIS) analysis on samples previously collected from subjects treated with Strimvelis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the precision of S-EPTS/LM-PCR methodology for RIS analysis using control insertion site DNA | Precision will be determined by the variability (%CV) of the abundance data. | post procedure up to 17 years, retrospective sample analysis | 
| To assess the accuracy of S-EPTS/LM-PCR methodology for RIS using control insertion site DNA | Accuracy will be determined based on the difference between the mean retrieved abundance and the expected abundance of control DNA. | post procedure up to 17 years, retrospective sample analysis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ada-scid, retroviral vector, gene therapy