eligibility_summary
Adults 18-75 with measurable, uniformly CD19/20+ B-cell malignancy (not primary CNS), relapsed/refractory after mandated prior regimens by subtype (DLBCL/FL ≥2, MCL after BTKi+anti-CD20+chemo, CLL/SLL after BTKi+venetoclax). ECOG 0-1, adequate counts/organ function, negative HBV/HCV, EF ≥50%. Washouts: ≥14 d systemic tx, ≥60 d anti-CD19/20, ≥180 d prior CAR-T. Exclude urgent mass effects, pregnancy, HIV, active infection, serious comorbidities, immunodeficiency, prior allo SCT, steroids/anticoagulants, CNS disease, recent checkpoint inhibitors.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase I NIH trial of Hu1928-Hu20BB-Long, an autologous bicistronic CAR T-cell gene therapy for relapsed/refractory B-cell malignancies. Patient T cells are engineered to express two fully human CARs: anti-CD19 with CD28/CD3ζ signaling (rapid activation/expansion) and anti-CD20 with 4-1BB/CD3ζ signaling (enhanced persistence). Dual targeting aims to prevent antigen-loss escape and eliminate malignant B cells, with expected B-cell aplasia. Conditioning uses cyclophosphamide (alkylating chemotherapy) and fludarabine (purine analog antimetabolite) to lymphodeplete and support CAR T expansion. Dose escalation: 0.66–10×10^6 CAR+ cells/kg. Targets/pathways: CD19 and CD20 on B cells, T-cell activation via CD28 and 4-1BB co-stimulation and CD3ζ signaling, triggering cytotoxic killing (perforin/granzyme). Primary focus: safety, monitoring for CRS and neurotoxicity.