eligibility_summary
Inclusion: ≥18 with demyelinating PNP, IgM MGUS and anti-MAG ≥10,000, functional impairment (INCAT ≥2), ECOG 0-2, adequate labs, prior IVIG >3 mo and anti-CD20/cyclophosphamide >6 mo allowed. Exclusion: hematologic malignancy/other recent cancer, stroke, CNS bleed or bleeding disorder, prior purines/BTKi, recent major surgery, pregnancy, other neuropathy causes, significant CV/ECG/GI disease, active HIV/HBV/HCV viremia/TB, strong CYP3A drugs, rituximab/zanubrutinib intolerance.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05939037 (MAGNAZ): Single‑arm, phase II study in IgM MGUS with anti‑MAG polyneuropathy testing zanubrutinib plus rituximab. Drugs/mechanisms: 1) Zanubrutinib is an oral small‑molecule Brutons tyrosine kinase (BTK) inhibitor (tyrosine kinase inhibitor) that blocks B‑cell receptor signaling, curbing survival/activation of the IgM‑secreting clone and lowering IgM and anti‑MAG antibodies, activity is expected in MYD88‑mutated clones. 2) Rituximab is an anti‑CD20 monoclonal antibody that depletes CD20+ B cells via immune effector mechanisms. Cells/pathways targeted: clonal IgM‑producing CD20+ B cells, BTK/B‑cell receptor/NF‑κB signaling axis, reduction of M‑protein and anti‑MAG titers to lessen antibody‑mediated nerve damage.