ALL-026: Evaluating Efficacy and Safety of Tisagenlecleucel Reinfusion Following Loss of B-Cell Aplasia in Pediatric and Young Adult Patients with Acute Lymphoblastic Leukemia: HESTER Phase II Study

Abstract

Context: In the ELIANA trial, tisagenlecleucel, a chimeric antigen receptor (CAR)-T cell therapy, demonstrated efficacy (81% overall remission rate [ORR]; 60% complete remission [CR]) and safety in pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) (Maude et al. N Engl J Med. 2018). Sustained remissions were associated with B-cell aplasia. In patients with short CAR-T cell persistence, reinfusion with tisagenlecleucel may restore B-cell aplasia in some patients (Maude et al. J Clin Oncol. 2016). Objective: To determine the efficacy and safety of tisagenlecleucel reinfusion in pediatric and young adult patients with B-ALL experiencing loss of B-cell aplasia. Design: HESTER (NCT04225676) is an ongoing phase II, open-label, multicenter trial being conducted in the United States. Clinical and laboratory assessments will be done at months 1, 3, 6, and 12 post-reinfusion. Patients: Eligible patients must be ≤25 years old, with CD19(+) B-ALL and a previous infusion of commercial tisagenlecleucel with ≥1 additional tisagenlecleucel dose available. Patients must exhibit loss of B-cell aplasia, defined as peripheral blood (PB) absolute B lymphocyte count ≥50/µL or PB B lymphocytes ≥10% of the total, but are not required to be minimal residual disease negative (MRD-). Patients with active central nervous system metastasis or treated with prior gene or other T-cell therapies are excluded. Estimated enrollment is approximately 54 patients. Interventions: Reinfusion with tisagenlecleucel will be given once during the study, with the dose range of 0.2-5.0×106 CAR-positive viable T-cells/kg for patients ≤50 kg body weight or 0.1-2.5×108 CAR-positive viable T-cells for patients >50 kg body weight. Reinfusion must occur within 9 months from manufacture. Main Outcomes Measures: The primary efficacy endpoint is the proportion of patients who reestablish B-cell aplasia (circulating B lymphocytes