eligibility_summary
Adults ≥18, ECOG 0–2, primary CNS lymphoma (or CNS-only secondary) with measurable disease/CSF+. Must have failed/intolerant to CNS-directed therapy, CD19+ if prior CD19 Rx. Prior CAR-T allowed ≥3 mo. Require adequate organ function and no active HIV/HBV/HCV. Exclude systemic lymphoma, unresolved tox, unstable arrhythmia, CNS inflammation/seizures, active autoimmune disease or infection, bleeding disorder, stroke/ICH <6 mo, steroids >4 mg, allergy, or noncompliance.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05625594 (Phase 1): Autologous CD19-directed CAR T cells (CD19CAR-CD28-CD3ζ-EGFRt), a gene‑modified cellular immunotherapy enriched for naïve/memory T cells, delivered intracerebroventricularly. Mechanism: CAR binds CD19 on B cells, CD28 costimulation and CD3ζ signaling activate cytotoxic T-cell killing, EGFRt serves as a tracking/safety tag enabling potential depletion with cetuximab. Lymphodepletion: cyclophosphamide (alkylating chemotherapy) and fludarabine (purine analog antimetabolite) to enhance CAR T expansion and persistence. Targets: CD19+ malignant B cells in the CNS (primary or CNS-only relapsed lymphoma), resulting in on-target B-cell aplasia, key pathways include CAR-mediated T-cell activation, expansion in CSF, and cytokine signaling.