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

Diffuse Large B-Cell Lymphoma (DLBCL), Follicular Lymphoma ( FL), High-grade B-cell Lymphoma (HGBCL), Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL), Relapsed/Refractory Non-Hodgkin Lymphoma

Relapsed/Refractory B-Cell Malignancies, B-Cell Acute Lymphoblastic Leukemia (B-ALL), Non-Hodgkin Lymphoma, High-Grade Lymphoma, Low-Grade Lymphoma, CD19, CAR-T Cell Therapy, Talikabtagene Autoleucel, Autologous T Cells, Adoptive Cell Therapy, Cytokine Release Syndrome (CRS), ICANS

The NexCAR19 study 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) 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 is supported by the Presidency of Turkish Health Institutes (TÜSEB) and will be conducted at four centers. This therapy is based on collecting the patient's own T cells, genetically modifying them in a laboratory to recognize the CD19 antigen, and reinfusing them into the patient. The goal is to target leukemia or lymphoma cells and achieve disease control. The primary objective is to assess the overall response rate at Day 28 after infusion and to evaluate the safety profile of the treatment. Secondary objectives include assessment of complete response rate, duration of response, overall survival, and progression-free survival, as well as the frequency and severity of cytokine release syndrome (CRS), neurotoxicity (ICANS), and other treatment-related adverse events. In addition, the in vivo persistence and immunological effects of CAR-T cells will be evaluated. Eligible patients must be 18 years of age or older, have an adequate performance status, sufficient organ function, and meet disease-specific eligibility criteria. Key exclusion criteria include active severe infection, uncontrolled cardiac disease, active central nervous system involvement (where applicable), HIV or active hepatitis infection, pregnancy, and severe immunodeficiency. The treatment process includes leukapheresis for cell collection, administration of lymphodepleting chemotherapy if required, followed by a single infusion of CAR-T cells. Patients will be closely monitored after infusion, particularly during the early period, and both early and late adverse events, as well as treatment response, will be regularly assessed. A total of 40 patients are planned to be enrolled. The overall clinical follow-up period, including short- and long-term monitoring, is expected to last approximately 30 months. Data will be analyzed using appropriate statistical methods.

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.

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