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