CD19 Sequential CD22 In Vivo CAR-T Cell Immunotherapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia - NCT07927816

This is a single-center, open-label, single-arm, prospective, investigator-initiated dose-escalation study to evaluate the safety, tolerability, preliminary efficacy, and cellular kinetics of an in vivo CAR-T cell immunotherapy targeting CD19 sequentially followed by CD22, in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). The investigational product is a targeted lentiviral vector that transduces the patient's endogenous T/NK cells in situ; no leukapheresis, ex vivo manufacturing, or lymphodepleting conditioning is required. Participants receive an intravenous infusion of CD19-targeted in vivo CAR-T on Day 0, followed by an intravenous infusion of CD22-targeted in vivo CAR-T on Day 7. Before the Day 7 infusion, the investigator will assess each participant to determine whether the second infusion should proceed, based on: (i) the proportion of CAR-positive T/NK cells in peripheral blood, which reflects the success of in vivo transduction and early expansion after the first infusion; (ii) the maximum grade and current control of adverse events occurring after the first infusion, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS); and (iii) the participant's general condition, including Eastern Cooperative Oncology Group (ECOG) performance status and vital organ function (cardiac, hepatic, renal, pulmonary, and coagulation). The second infusion will be postponed or cancelled if any of these assessments indicates that the risk outweighs the benefit, for example grade \>=3 CRS or grade \>=2 ICANS that has not resolved to grade \<=1, or investigator-judged deterioration in organ function. Dose escalation follows a traditional 3+3 design with planned dose levels of 1×10\^9, 3×10\^9, and 6×10\^9 transducing units (TU), guided by dose-limiting toxicities (DLTs) assessed during Days 0-28; higher dose levels may be explored if the maximum tolerated dose is not reached. Treatment-emergent adverse events and serious adverse events, including CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, and organ toxicity, will be assessed. Preliminary antitumor activity will be evaluated by objective response rate (ORR), overall survival (OS), and progression-free survival (PFS), and the expansion and persistence of in vivo-generated CAR-T cells in peripheral blood will also be evaluated.