eligibility_summary
Adults (≥18) with Richter’s syndrome (DLBCL from CLL/SLL), relapsed/refractory after ≥1 regimen or arising on CLL therapy, ECOG ≤2, adequate organ function (hepatic, renal), LVEF ≥40%, adequate marrow (allowances if marrow involved), measurable disease, contraception. Exclude prior CD19 therapy, recent allo‑SCT/GVHD, active bleeding/ulcer, major CVD, HIV, active HBV/HCV, uncontrolled illness, CYP3A modifiers, pregnancy/breastfeeding, autoimmune on IS, chronic steroids ≥20 mg, live vaccines ≤28 d, myelodysplasia.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II single-arm trial in Richter’s syndrome tests zanubrutinib (Brukinsa), an oral small‑molecule Bruton’s tyrosine kinase (BTK) inhibitor that blocks B‑cell receptor signaling and proliferation, combined with lisocabtagene maraleucel (liso‑cel, Breyanzi), an autologous anti‑CD19 CAR T‑cell therapy (CD4+ and CD8+ T cells with 4‑1BB costimulatory domain) that targets and kills CD19+ malignant B cells. Patients receive lymphodepleting fludarabine (purine analog antimetabolite) and cyclophosphamide (alkylating agent) prior to liso‑cel. Targets/pathways: BTK/BCR signaling in CLL/DLBCL cells, CD19 on B cells, T‑cell activation and persistence, inflammatory cytokine pathways, tumor microenvironment.