NexCAR19 (Talikabtagene Autoleucel) in Relapsed/Refractory B-Cell Malignancies (NexCAR19)

This study (NexCAR19) is a national, open-label, multicenter Phase 2-3 clinical trial designed to evaluate the efficacy and safety of the anti-CD19 chimeric antigen receptor (CAR) autologous T-cell product, Talikabtagene Autoleucel, in patients with relapsed/refractory B-cell malignancies, including B-cell Acute Lymphoblastic Leukemia (B-ALL) and Non-Hodgkin Lymphoma. The study will be conducted at four centers with the support of the Presidency of Turkish Institutes of Health (TÜSEB). The primary objective is to assess the overall response rate and safety profile of CD19-targeted CAR-T cell therapy. Secondary objectives include evaluation of complete response rates, duration of response, overall survival (OS), event-free survival (EFS), progression-free survival (PFS), relapse-free survival (RFS), as well as the incidence and severity of cytokine release syndrome (CRS) and neurotoxicity (ICANS). Additional assessments include immunological effects such as B-cell aplasia and hypogammaglobulinemia, along with in vivo persistence and expansion of the infused CAR-T cells. Eligible patients will be adults aged 18 years or older with an ECOG performance status of 0-2, an expected life expectancy of at least 12 weeks, and who meet disease-specific eligibility criteria for the relevant subgroup. Patients must have adequate organ function, provide written informed consent, and use appropriate contraception methods. Additional inclusion criteria are defined for high-grade lymphoma, low-grade lymphoma, and B-ALL subgroups. Key exclusion criteria include active infection, uncontrolled cardiac disease, active central nervous system involvement (in relevant subgroups), HIV positivity, active hepatitis infection, pregnancy, severe immunodeficiency, and any condition deemed unsuitable by the investigator. The treatment process includes leukapheresis for cell collection, administration of lymphodepleting chemotherapy if required, followed by a single infusion of CD19 CAR-T cells. Patients will be closely monitored during the early post-infusion period, particularly within the first 10 days for signs of cytokine release syndrome. Short- and long-term follow-up assessments will include clinical response evaluation, imaging (PET/CT and Lugano criteria for lymphoma), bone marrow evaluation and minimal residual disease analysis (for B-ALL), immunological testing, and transgene detection (qPCR) to monitor CAR-T cell persistence. The primary endpoint is the overall response rate at Day 28 following infusion. Secondary endpoints include response rates at Days 90 and 180, complete remission rate, survival analyses, relapse rate, evaluation of CRS and other adverse events, and analysis of cellular and immunological parameters. A total of 40 patients are planned to be enrolled. The overall study duration is expected to be 30 months, including 6 months for patient recruitment, 3 months for infusion and short-term follow-up, and 21 months for long-term follow-up. Statistical analyses will include descriptive statistics, appropriate parametric and non-parametric tests, correlation analyses, and Kaplan-Meier survival analysis. A p-value of \<0.05 will be considered statistically significant.