A Phase II Study to Evaluate the Efficacy of UF-KURE19 Cells in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

This is a Phase II, single-arm, open-label, interventional study designed to evaluate the efficacy of UF-KURE19, an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). UF-KURE19 is manufactured using an ultra-fast production process completed in under one day, in contrast to conventional CAR-T manufacturing timelines. The study aims to determine whether this accelerated manufacturing approach can deliver an effective CAR-T product while addressing logistical and clinical challenges associated with longer production times, such as disease progression during the manufacturing wait period.

The trial enrolls two distinct cohorts based on lymphoma subtype and treatment history. Cohort 1 will enroll 81 participants with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma not otherwise specified, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, or follicular lymphoma grade 3B. Eligible LBCL patients must have relapsed after two or more prior lines of chemoimmunotherapy, have disease refractory to first-line therapy or relapsing within 12 months of completing initial chemoimmunotherapy, or have relapsed disease and be ineligible for hematopoietic stem cell transplantation due to comorbidities, age, or patient preference. Cohort 2 will enroll 24 participants with follicular lymphoma or marginal zone lymphoma who have relapsed after two or more prior lines of therapy.

All participants must have histologically confirmed CD19-positive NHL (by immunohistochemistry or flow cytometry) at the most recent biopsy; patients previously treated with CD19-targeted therapy must have a post-treatment biopsy confirming sustained CD19 expression. Additional eligibility requirements include an ECOG performance status of 2 or better, measurable disease with at least one FDG-avid lesion per Lugano Criteria, and adequate hepatic, renal, cardiac, and pulmonary function. Patients must be at least two weeks removed from prior radiation or systemic anti-malignancy therapy and at least 28 days (or five half-lives, whichever is shorter) from any investigational agent prior to leukapheresis. Women of childbearing potential and men with partners of childbearing potential must agree to use highly effective contraception during and after treatment, as specified in the protocol.

Key exclusion criteria include prior allogeneic hematopoietic stem cell transplant, autologous stem cell transplant within 12 weeks of consent, active second malignancies (with limited exceptions), NYHA Class III-IV heart failure, recent cardiovascular events, active HIV or hepatitis B/C infection, pregnancy or breastfeeding, clinically significant CNS pathology, uncontrolled intercurrent illness, active autoimmune disease requiring significant immunosuppression, leukemic phase lymphoma, and prior treatment with any CD19-directed CAR-T product.