A Clinical Study Evaluating the Safety and Efficacy of Universal CD19-Targeted CAR-T (UWD-CD19) Therapy for Refractory and Relapsed B-Cell Tumors
This study is a single-arm, single-center, investigator-initiated clinical trial. The primary objective is to evaluate the safety and preliminary efficacy of administering universal CD19 CAR-T cells to subjects with refractory and relapsed B-cell tumors. Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning after signing an informed consent form, followed by a one-time injection of universal UWD-19 to assess its safety and efficacy. Subjects will be hospitalized for a period, and after discharge, they will undergo periodic efficacy assessments and long-term survival follow-up for at least five years.
• Patients (or their guardians) understand the study and voluntarily sign the informed consent form, with an expected ability to complete follow-up evaluations and treatments as per study protocol.
⁃ Age range: 3-70 years, no gender restrictions. Diagnosis of B-cell lymphoma, meeting the 2018 NCCN B-Cell Lymphoma guidelines (Version 5), with CD19 positivity confirmed by flow cytometry or immunohistochemistry.
⁃ At least one evaluable or measurable lesion per Lugano 2014 criteria. Evaluable lesions are indicated by FDG uptake above liver levels on FDG/PET or by lymphoma-like characteristics on PET/CT. Measurable lesions require a nodal diameter \>15 mm or extranodal lesion \>10 mm (with post-radiation evidence of progression if previously irradiated). Cases without measurable lesions but with diffuse liver FDG uptake are excluded.
⁃ Refractory and relapsed B-cell lymphoma, meeting at least one of the following: a. Received ≥2 cycles of standardized second-line or higher treatment, and meets Lugano 2014 criteria for best clinical response:
⁃ Progressive Disease (PD) on the most recent treatment.
⁃ Stable Disease (SD) lasting \<6 months before progressing. b. Recurrence or progression ≤12 months post-autologous stem cell transplant. c. Based on investigator judgment, the potential benefit may outweigh risk in cases such as:
⁃ Recent SD with measurable disease progression but not meeting PD criteria. Partial remission (PR) or better lasting \<6 months post-treatment, then progression.
⁃ Intolerance to most recent chemotherapy. Relapsed/refractory CD19-positive acute B lymphoblastic leukemia.
⁃ Laboratory values indicating adequate organ and marrow function, with no severe cardiac, pulmonary, hepatic, renal, or immune dysfunction:
⁃ Serum albumin ≥25 g/L Creatinine clearance ≥30 mL/min/1.73 m² ALT and AST ≤3.0× ULN Total bilirubin ≤2.0× ULN (exceptions for congenital hyperbilirubinemia like Gilbert syndrome with direct bilirubin ≤1.5× ULN) PT and APTT \<2× ULN Oxygen saturation ≥95% Blood transfusions allowed to maintain hemoglobin ≥8.0 g/dL. ECOG performance status 0-1. Expected survival time \>90 days. Negative β-hCG test for women of childbearing potential at screening and prior to chemotherapy.
⁃ Women of childbearing potential must use a highly effective contraceptive method (annual failure rate \<1%) from the time of consent until 1 year after UWD-CD19 infusion, including:
⁃ Non-user-dependent: implantable progestogen, IUD, hormone-releasing system, or partner vasectomy.
⁃ User-dependent: combination hormonal contraception, progestogen-only pill, or injection.