Phase I/II Clinical Trial of Autologous Hematopoietic Stem Cell Gene Therapy in RAG1-Deficient Severe Combined Immunodeficiency
This study is a prospective, non-randomized, open-label, two-centre phase I/II intervention study designed to treat children up to 24 months of age with RAG1-deficient SCID with an indication for allogeneic hematopoietic stem cell transplantation but lacking an HLA-matched donor. The study involves infusion of autologous CD34+ cells transduced with the pCCL.MND.coRAG1.wpre lentiviral vector (hereafter called RAG1 LV CD34+ cells) in five patients with RAG1-deficient SCID.
• RAG1-deficient SCID as confirmed by genetic analysis
• Peripheral blood T cells \< 300/μL and/or naïve T cells \< 1/μL
• Age \< 2 years
• Age at least 8 weeks by the time of busulfan and fludarabine administration
• Lack of an available HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
• Signed informed consent (parental or guardian)
• Able to return to the study centre for follow-up (per protocol) during the 2-year study and the 15-year long-term off study review