A Phase I Clinical Trial for Gene Therapy in Infantile Malignant Osteopetrosis (IMO) to Evaluate the Safety and Preliminary Efficacy of Autologous CD34+ Enriched Cells Transduced With a LV Vector Encoding the TCIRG1 Gene

Fecha de inicio: 19 de noviembre de 2020

Inclusion Criteria: 1. A confirmed diagnosis of IMO with documented TCIRG1 mutation. 2. Age at least 1 month with minimum weight of 4 kg 3. Absence of debilitating hydrocephalus (defined as hydrocephalus at NCI CTCAE v5.0 Grade 3 or higher persisting despite shunt or similar procedural intervention). 4. Lansky Play Scale of at least 60% 5. Preserved hepatic function (AST/ALT ≤3.0 ULN; bilirubin ≤1.5 ULN; to minimize potential for excessive toxicity from busulfan conditioning) 6. No concomitant medical or other conditions that would represent a contraindication to autologous hematopoietic stem cell transplant. 7. Absolute neutrophil count of ≥500/mm3 and platelet count of ≥25,000/mm3 8. No prior allogeneic or other hematopoietic stem cell transplant. 9. Availability of a non-autologous rescue (back-up) hematopoietic stem cell donor/source Exclusion Criteria: 1. Availability of medically-feasible HLA-matched sibling donor for allogeneic HSCT. 2. Any medical or other contraindication for either apheresis or autologous transplant as determined by the Investigator. 3. Participation in another clinical trial with an investigational drug within 14 days before the informed consent signature. Participation in observational studies is allowed. 4. Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or another carcinoma in situ. 5. Uncontrolled seizure disorder. 6. Renal dysfunction as defined by a glomerular filtration rate \<30 mL/min/1.73m2 or dialysis dependence. 7. Serious infections with persistent bloodstream pathogens at time of trial entry 8. Pulmonary dysfunction as defined by either: * Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection) or * Oxygen saturation (by pulse oximetry) \<90% resulting from pulmonary conditions (intermittent hypoxia secondary to IMO-related choanal atresia will not be considered exclusionary)