eligibility_summary
Adults ≥18 with measurable, biopsy‑proven R/R large B‑cell lymphoma (DLBCL/PMBCL/transformed FL) after ≥2 lines, eligible/stable for CAR‑T, ECOG 0–1, adequate organs, no active CNS disease, HIV/HBV/HCV negative, ≥2 wks from prior therapy, acceptable apheresis. Exclude bulk ≥10 cm post‑bridging, prior CD19/CAR‑T/allogeneic SCT, uncontrolled infection/TB, major cardiac/pulmonary/autoimmune/CNS disorders, recent malignancy, pregnancy/live vaccine, contraception required.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: Phase 1b (withdrawn) testing optimized lymphodepletion before tisagenlecleucel (Kymriah) in R/R large B‑cell lymphoma. Interventions: 1) Cyclophosphamide (alkylating prodrug, DNA crosslinking cytotoxic chemo) at standard/intermediate/high doses. 2) Fludarabine (purine analog antimetabolite, inhibits DNA polymerase/ribonucleotide reductase → lymphocyte apoptosis), fixed dose. 3) Optional total lymphoid irradiation (TLI, low‑dose radiation to lymphoid tissues) to augment lymphodepletion. Mechanistic goal: Deplete host lymphocytes (T and B cells), regulatory T cells, and NK cells, reduce immune competition, and increase homeostatic cytokines (IL‑7/IL‑15) to enhance CAR T expansion/persistence. Cell/pathway target: Kymriah is an autologous anti‑CD19 CAR T‑cell therapy (4‑1BB/CD3ζ) that kills CD19+ malignant B cells.