Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone for for Richter Syndrome Transformed From CLL

This single-arm, multicenter, open-label phase II trial evaluates the efficacy and safety of rituximab + pirtobrutinib + lisaftoclax + liposomal mitoxantrone in adults with CLL-transformed Richter syndrome (CLL-RS). All eligible patients receive 4 cycles (21 days each) of the quadruple regimen: rituximab 375 mg/m² IV on Day 0, pirtobrutinib 200 mg PO daily (D1-21), lisaftoclax ramp-up to 600 mg QD (D1-21), and liposomal mitoxantrone 18 mg/m² IV on D1, with TLS prophylaxis/monitoring. Primary endpoint: CR rate after 4 cycles. Secondary endpoints: ORR, DOR, PFS, OS, MRD negativity, and safety. Post-induction: CR/PR patients proceed to allo-HSCT, CAR-T, or maintenance; SD/PD receive alternative/palliative care. Long-term follow-up starts after discontinuation.