pCCLCHIM-p47 (Lentiviral Vector Transduced CD34 Plus Cells) in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease (AR-CGD)

Study Description: This is a phase I/II, non-randomized, open-label study of a single infusion of autologous CD34+ cells transduced ex vivo with pCCLCHIM-p47 in 5 patients with p47-AR CGD conditioned with high dose busulfan. Objectives: Primary Objectives: To evaluate the efficacy of pCCLCHIM-p47 transduced autologous CD34+ cells treatment in p47 AR-CGD patients as measured by engraftment of genetically modified cells at 6 months. Secondary Objectives: * Safety * Long term engraftment (assessments at 1 year, 2 years, and 3 years) * Event Free Survival * Clinical Efficacy and Health Assessment Exploratory Objectives: * Assessment of biomarker utility * Evaluation of the human microbiome during pCCLCHIM-p47 gene therapy. * Patient reported assessment of efficacy (QOL) Endpoints: Primary Endpoint of this study will be engraftment of genetically modified cells as defined by presence of \>10% oxidase positive cells at 6 months. * Secondary Endpoints will consist of: * Safety: assessed by recording of the incidence of adverse events. * Record clinical adverse events and clinically significant laboratory abnormalities. * Evaluate overall incidence of adverse events for the study as a whole. * Monitor the incidence of serious adverse events. * Measure overall survival at 3 years post-transplant * Assessment of vector safety by vector insertion site analysis (VISA) and replication competent lentivector (RCL) testing. * Long term multilineage engraftment, as measured by: * Expression of p47 phox in neutrophils at 6, 12, 18, 24, and 36 months. * Hematological reconstitution by 90 days post treatment (absolute neutrophil count \>500 cells/microliter on three consecutive samples over at least ten days). * NADPH Oxidase activity in monocytes by dihydrorhodamine (DHR) flow cytometry at 6, 12, 18, 24, and 36 months. * Percentage of gene modified CD34+ hemopoietic cells in BM at 6, 12, 18, 24, 30, and 36 months as assessed by vector copy number (VCN) qPCR. * VCN in cell lineages present in PB cells at months 1, 3, 6, 9, 12, 18, 24, and 36. * Event free Survival * Resolution of either underlying inflammation and/or infection related to P47 deficiency without recurrence for 3 years. * Rate of severe (as defined by CTCAE v 5.0 - grade 3 to 5) CGD related infections after withdrawal of antimicrobial prophylaxis in time periods 6-12 and 6-36 months post treatment. * Assessment of clinical efficacy and health by: * The nutritional status (height, weight, serum albumin) at 36 months. * Growth and development of pediatric subjects at 36 months. * Frequency of severe infections (days requiring IV antibiotics and/or hospitalization for treatment) at 36 months. * Presence of inflammatory complications (days requiring hospitalizations) at 36 months. Tertiary Endpoints: * Utility of Biomarker assessment * Stool collection for microbiome analysis (optional) * Patient Quality of life questionnaire collection