T cells modified to express a chimeric-antigen receptor (CAR)targeting CD19 can induce potent and sustained responses in children with relapsed/refractory acute lymphoblastic leukemia (ALL). The durability of remission is related to the length of time the CAR T cells persist. Efforts to understand differences in persistence have focused on the CAR construct, in particular the co-stimulatory signaling module of the chimeric receptor. We previously reported a robust intent-to-treat product manufacturing success rate and remission induction rate in children and young adults with recurrent/refractory B-ALL using the SCRI-CAR19v1 product, a 2nd generation CD19-specific CAR with 4-1BB costimulation co-expressed with the EGFRt cell surface tag (NCT02028455). Following completion of the phase 1 study, two changes to CAR T-cell manufacturing were introduced: switching the T-cell activation reagent and omitting mid-culture EGFRt immunomagnetic selection. We tested the modified manufacturing process and resulting product, designated SCRI-CAR19v2, in a cohort of 21 subjects on the phase 2 arm of the trial. Here, we describe the unanticipated enhancement in product performance resulting in prolonged persistence and B-cell aplasia, and improved leukemia-free survival with SCRI-CAR19v2 as compared to SCRI-CAR19v1.