This is a Phase 1/2, open label, safety, and efficacy study of the administration of LentiGlobin BB305 Drug Product to subjects with either beta-thalassemia major or severe sickle cell disease (SCD).
Name: LentiGlobin BB305 Drug Product
Description: autologous CD34+ hematopoietic stem cells (HSCs) transduced with the LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene Subjects with beta-thalassemia major will undergo HSC procurement by bone marrow harvest or apheresis after mobilization with filgrastim, a granulocyte-colony stimulating factor (G-CSF), alone or in combination with plerixafor, as decided by the clinical transplant team. Stem cell mobilization by is contraindicated in sickle cell disease (SCD), as it could induce a sickle cell crisis; thus, procurement of HSCs for subjects with severe SCD will be conducted by bone marrow harvest.Type: GeneticLentiGlobin BB305 Drug Product
Description: AEs assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
Measure: Monitoring of laboratory parameters and frequency and severity of clinical AEs Time: 1-24 months post-transplantDescription: Therapeutic globin expression, as measured by assessing the ratio of beta A-T87Q-globin to alpha-globin in whole blood, as well as the amount of beta A-T87Q-globin as a fraction of all beta-chains in whole blood
Measure: Quantify gene transfer efficiency and expression by evaluation Time: 1-24 months post-transplantDescription: Average vector copy number (VCN) in cell populations from peripheral blood and bone marrow containing the integrated LentiGlobin BB305 lentiviral vector.
Measure: Quantify gene transfer efficiency and expression by evaluation Time: 1-24 months post-transplantDescription: For all subjects, red blood cell (RBC) transfusion requirements (measured in milliliters [mL] per kilogram [kg]) per month and per year post transplant
Measure: Efficacy Time: 1-24 months post-transplantDescription: For sickle cell disease (SCD) subjects only, vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) events in each subject compared with the 2 year pre-treatment period
Measure: Efficacy Time: 1-24 months post-transplantSingle Group Assignment
There is one SNP
A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the Beta-Hemoglobinopathies (Sickle Cell Disease and Beta-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral Beta-A-T87Q Globin Vector (LentiGlobin BB305 Drug Product). --- T87Q ---
Therapeutic globin expression, as measured by assessing the ratio of beta A-T87Q-globin to alpha-globin in whole blood, as well as the amount of beta A-T87Q-globin as a fraction of all beta-chains in whole blood. --- T87Q ---
Therapeutic globin expression, as measured by assessing the ratio of beta A-T87Q-globin to alpha-globin in whole blood, as well as the amount of beta A-T87Q-globin as a fraction of all beta-chains in whole blood. --- T87Q --- --- T87Q ---