eligibility_summary
Adults ≥18 with WM, untreated or minimally pretreated (no BTKi/BR/RCD/VRD/CHOP/COP/fludarabine, chlorambucil/cyclophosphamide ≤4 wks, no MR, 2‑wk washout). Must need therapy (e.g., hyperviscosity, neuropathy, cytopenias, B symptoms, rapid progression). ECOG ≤2, ANC ≥0.75, PLT ≥50 (×10^9/L), bilirubin ≤2.5×ULN, AST/ALT ≤3×ULN, CrCl ≥30, life ≥3 mo. Exclude: other recent cancers, large‑cell transformation, major organ dysfunction, serious comorbidities, HIV/active HBV/infection, CNS involvement, recent major surgery, malabsorption, strong CYP3A inhibitors, pregnancy/lactation, drug allergy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II single-arm trial in newly diagnosed symptomatic Waldenström macroglobulinemia testing time‑limited zanubrutinib + bendamustine + rituximab (ZBR), then zanubrutinib maintenance. Drugs/mechanisms: Zanubrutinib—small‑molecule, covalent Bruton tyrosine kinase (BTK) inhibitor, blocks B‑cell receptor (BCR) signaling and survival pathways in malignant lymphoplasmacytic/IgM‑secreting B cells. Bendamustine—alkylating (nitrogen mustard) chemotherapeutic with antimetabolite properties, DNA crosslinking → apoptosis of proliferating B cells. Rituximab—chimeric anti‑CD20 monoclonal antibody, depletes CD20+ B cells via CDC/ADCC/apoptosis. Targets: BTK/BCR signaling (key driver in WM), CD20 on lymphoplasmacytic cells, and tumor DNA integrity/cell cycle. Goal: deepen responses and prolong remission with a finite therapy to reduce long‑term BTKi exposure, resistance, and toxicity.