Universal CAR-T Cells (REVO-UWD-19) for Refractory and Relapsed B-Cell Tumors

Prior treatment

• History of aggressive malignancies other than B-cell lymphoma, except:
  • Cancer in remission >2 years post-curative therapy. Non-melanoma skin cancer successfully treated and inactive.
  • Prior anti-cancer therapy including:
  • Targeted, epigenetic, or experimental drug therapy within 14 days or 5 half-lives.
  • Cytotoxic therapy within 14 days. Immunomodulators within 7 days. Monoclonal antibodies within 21 days. Radiotherapy within 14 days. Active CNS involvement. Conditions like Waldenström's macroglobulinemia, POEMS syndrome, or primary AL amyloidosis.
  • Active hepatitis B (HBsAg or HBcAb positive with viral load >1000 copies/ml), hepatitis C (HCV RNA positive), HIV, CMV, or syphilis positivity.
  • Severe allergy history, or known allergy to trial components, adjuvants, or animal-derived proteins.
  • Severe cardiac conditions such as arrhythmias, unstable angina, recent MI, heart failure (NYHA III/IV), uncontrolled hypertension.
  • Unstable systemic disease, including significant liver, kidney, or metabolic disease requiring medication.
  • Acute/chronic GVHD or requiring immunosuppressants within 6 months. Active autoimmune or inflammatory neurologic diseases. Urgent tumor-related conditions requiring emergency treatment. Uncontrolled bacterial, fungal, or viral infections. Major surgery within 4 weeks or planned major surgery during the study. Live virus vaccination within 4 weeks prior to screening. Severe psychiatric disorders. History of substance abuse. Pregnant or lactating women, or individuals planning conception within 2 years of cell infusion.
  • Any contraindications per investigator's judgment due to clinical standards or patient's condition.

• 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.