Study Treatment Schedule Sample Clauses

Study Treatment Schedule. 6.3.1. Leukapheresis (Within Approximately 5 Days of Eligibility Confirmation) 6.3.3.1. Dosing Rationale Administration of conditioning chemotherapy correlates with clinical responses to adoptive cell therapy (Xxxxxx et al, 2008). Specifically, there appears to be a link between adequate lymphodepletion and adoptively-transferred T-cell expansion and function. The depth and duration of the lymphodepletion in pre-clinical models correlate with the anti-tumor activity of the adoptively-transferred, tumor-specific CD8+ T cells (Xxxxxxxxx et al, 2005). Lymphodepletion may function by eradicating cytokine sinks for the transferred cells, eliminating regulatory T cells, or enhancing the activation of antigen-presenting cells (Xxxxxxxxx et al, 2005). Combined treatment with cyclophosphamide and fludarabine represents a potent lymphodepleting regimen. The ZUMA-1 study of axicabtagene cilouleucel in aggressive large B-cell lymphoma used the same cyclophosphamide/fludarabine conditioning regimen that is being used in the ZUMA-2 study (axicabtagene ciloleucel USPI). This regimen was tolerated prior to infusion of the cellular product and resulted in a favorable risk‑benefit profile. Similar doses of cyclophosphamide and fludarabine have been administered to subjects with B-cell malignancies prior to anti-CD19 CAR T cell infusion (NCI Protocol 09‑C‑0082) (Xxxxxxxxxxxx et al, 2016) and were shown to increase levels of cytokines known to support T-cell expansion and survival (Xxxxxxxxxxxx et al, 2017). This treatment combination was also used as a reduced non-myeloablative conditioning regimen for patients with B-cell malignancies who were undergoing alloSCT and resulted in tolerable toxicities (Xxxxxx et al, 1998).