NCT03311503

Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: David Williams · Academic / Other
• Sex: Male
• Age: 0 Years – 5 Years
• Healthy volunteers: Not accepted

Summary

This is a phase I/II open label multi-center study in which patients will receive low dose targeted busulfan followed by infusion of autologous CD34+ selected bone marrow or mobilized peripheral blood cells transduced with the G2SCID vector. Subjects will be enrolled over 3 years and be followed for 2 years post-infusion on this protocol, then followed long-term on a separate long-term follow-up protocol. Enrollment of subjects will be agreed upon by representatives of both sites. Data will be collected uniformly from both sites through an electronic capture system and key laboratory studies will be centralized. Harvest, cellular manufacturing and infusion will occur at each site using the same SOPs. Key aspects of cellular product characterization will be centralized

Detailed description

This is an open labeled, multi-center, phase I/II, cohort study involving a single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID in up to 10 patients with X-linked SCID (SCID-X1) at Boston Children's Hospital, UCLA Mattel Children's Hospital, Cincinnatti Childrens Hospital Medical Center, Children's Healthcare of Atlanta. Patients will receive transduced cells after low dose targeted busulfan pre-conditioning (n=12). Enrolled subjects will be followed for 2 years after infusion on this protocol. Required long-term monitoring for a total of 15 years after infusion will be performed on a separate protocol. Single infusion of autologous CD34+ cells transduced with the SIN lentiviral vector rHIV\_IL2RGcoG2SCID (hereafter G2SCID) The primary objective is to measure event free survival and T cell immune reconstitution at 1 year post-infusion Secondary objectives are to measure overall survival, event-free survival, safety related to the procedure, and clinical and laboratory measures of efficacy including humoral immune reconstitution and gene marking after gene transfer. Exploratory objectives include: molecular characterization of gene transfer, detailed assessment of biomarkers of T and B cell development and function, assessment of infections, nutritional status, growth and development post gene therapy, assessment of T cell receptor and B cell receptor repertoire by next generation sequencing, correlation of busulfan levels with immune outcome and molecular measurements of gene transfer

Conditions

• Severe Combined Immunodeficiency, X Linked
• Gene Therapy

Interventions

Type	Name	Description
BIOLOGICAL	autologous CD34+ cell transduced with G2SCID vector	single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID

Timeline

• Start date: 2018-02-26
• Primary completion: 2028-01-01
• Completion: 2028-01-01
• First posted: 2017-10-17
• Last updated: 2025-12-11

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study