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.
All participants must meet Inclusion Criteria 1-13.
High-grade lymphoma subjects must meet Criteria 14-18.
Other B-cell lymphoma subjects must meet Criteria 19-24.
B-ALL subjects must meet Criteria 25-29.
All participants must meet Exclusion Criteria 1-14.
High-grade lymphoma: 15-22
Low-grade lymphoma: 23-24
B-ALL: 25
Single group
Talikabtagene Autoleucel
Biological/VaccineTalikabtagene Autoleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy. Peripheral blood mononuclear cells are collected via leukapheresis, genetically modified to express an anti-CD19 CAR, expanded ex vivo, and infused intravenously after lymphodepleting chemotherapy.
Overall Response Rate (ORR) to CD19 CAR-T cell product at Day 28 post-infusion
Evaluation of Overall Response Rate (ORR) at Day 28 following infusion of the CD19 CAR-T cell product: In patients with relapsed/refractory (r/r) B-ALL, response will be assessed by morphological bone marrow (BM) analysis at Day 28, and minimal residual disease (MRD) will be evaluated using flow cytometry. In patients with relapsed/refractory (r/r) B-cell lymphoma, treatment response will be assessed by PET/CT according to the Lugano criteria. Duration of Response (DoR): Defined as the time from the date of first documented response to the date of disease progression or death, whichever occurs first.
Complete Remission (CR) Rate
The proportion of participants achieving complete remission following CAR-T cell infusion. For participants with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), response will be assessed by morphological bone marrow evaluation and minimal residual disease (MRD) assessment using flow cytometry. For participants with relapsed/refractory B-cell lymphoma, response will be assessed by PET/CT according to the Lugano classification criteria. Unit of Measure: Percentage of participants
Overall Response Rate (ORR)
The proportion of participants achieving an overall response following CAR-T cell infusion. ORR includes complete response (CR), complete response with incomplete hematologic recovery (CRi), and partial response (PR). For participants with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), response will be assessed by morphological bone marrow evaluation and minimal residual disease (MRD) assessment using flow cytometry. For participants with relapsed/refractory B-cell lymphoma, response will be assessed by PET/CT according to the Lugano classification criteria. Unit of Measure: Percentage of participants
Incidence of Cytokine Release Syndrome (CRS) and associated serum cytokine profile within 10 days post-infusion
Evaluation of serum cytokine profile within the first 10 days following CAR-T infusion to assess its association with the development of CRS.
Incidence and duration of B-cell lymphopenia and hypogammaglobulinemia
Assessment of the incidence and duration of B-cell lymphopenia (BCL) and hypogammaglobulinemia, and evaluation of their correlation with maintenance of complete response.
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