A First-In-Human Clinical Trial of Lentiviral-mediated CSF2RA Gene Transfer/Pulmonary Macrophage Transplantation Therapy of Hereditary Pulmonary Alveolar Proteinosis
Children's Hospital Medical Center, Cincinnati
Summary
The major goal of this study is to evaluate a new type of cell transplantation therapy for individuals with hereditary PAP, study a new treatment that may be useful for treatment of other diseases, and research mechanisms that drive the development and function of lung macrophages.
Description
Hereditary pulmonary alveolar proteinosis (hPAP) is a rare lung disease characterized by the progressive accumulation of pulmonary surfactant in alveoli resulting in progressive hypoxemic respiratory failure, and in some patients, secondary infections and/or pulmonary fibrosis. While hPAP affects men, women, and children, most patients present as children. The lung structure appears well-preserved in many cases with pathogenesis being driven by the consequences of the filling of alveoli with surfactant sediment; however, some patients develop respiratory failure caused by pulmonary fibrosis re…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Patients must meet all of the following conditions to be eligible for participation in this study: 1. Male or female with a confirmed diagnosis of hPAP defined as: * Homozygous or compound heterozygous CSF2RA mutations - AND - * A normal GM-CSF autoantibody test result - AND - * An abnormal STAT5-PI test result - OR - * An abnormal GM-CSF 50% effective concentration (EC50) test result 2. Diffuse ground glass opacification of the lungs visualized on a chest computed tomogram (CT) 3. History of prior receipt of WLL therapy or moderate hPAP lung disease severity…
Interventions
- Combination ProductGene-Corrected Macrophages administered by bronchoscopic instillation
This study will evaluate administration of autologous bone marrow CD34+ cell-derived, CSF2RA lentiviral vector-transduced macrophages (CSF2RA gene-corrected macrophages) by bronchoscopic instillation into individual lung segments on three occasions at 2-month intervals in patients with hPAP. The target (maximum) number of cells to be administered is 778 million gene-corrected macrophages per 70 kg patient, which is equal to 11.1 million cells/kg of ideal body weight.
Location
- Cincinnati Children's Hospital Medical CenterCincinnati, Ohio