Study of Nivolumab Combined With Tisagenlecleucel Reinfusion for Children, Adolescents, and Young Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia After Early Loss of CAR T-Cell Persistence

What this Trial Is About

Researchers are evaluating the combination of Nivolumab Opdivo4 with tisagenlecleucel CTL019, an anti-CD19 CAR T-cell therapy, in children, adolescents, and young adults aged 1 to 25 years who have relapsed or refractory B-cell Acute Lymphoblastic Leukemia B-ALL. The study focuses on patients who previously received tisagenlecleucel but experienced early loss of B-cell aplasia within 6 months, which indicates loss or non-functionality of the CAR T-cells and a high risk of relapse. The trial aims to determine the safety, efficacy, and best timing for starting Nivolumab to help improve CAR T-cell persistence and leukemia control. Participants receive lympho-depleting chemotherapy with Fludarabine and Cyclophosphamide followed by a reinfusion of tisagenlecleucel 2 to 14 days after chemotherapy. Nivolumab is administered intravenously at 3 mgkg every 2 weeks, beginning at one of several tested time points day 14, 11, 5, or -1 for patients with minimal residual disease MRD negative status, or starting at day -1 for relapsed patients. Nivolumab treatment continues for up to 12 months after tisagenlecleucel infusion if there is a response. During the study, participants are monitored for limiting toxicities at day 28 and for effectiveness by measuring MRD-negative complete remission and B-cell aplasia at 3 months. Additional assessments include the duration of B-cell aplasia, disease response, survival rates, and adverse events up to 2 years. Patients undergo regular blood and marrow evaluations to track leukemia status and immune recovery, with safety monitored closely throughout the treatment period and long-term follow-up.

Combination of an Anti-PD1 Antibody With Tisagenlecleucel Reinfusion in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia After Loss of Persistence