ZANUBRUTINIB for Peripheral anti-MAG neuropathy|Waldenström macroglobulinemia|Marginal zone lymphoma|Chronic lymphocytic leukemia|Monoclonal gammopathy of undetermined significance

Inclusion criteria

• {"criterion_text":"- ● Age ≥18 years;\n- ● diagnosis of anti-MAG antibody polyneuropathy;\n- ● diagnosis of anti-MAG antibody polyneuropathy;\n- ● IgM monoclonal protein underlying MGUS, Waldenstrom macroglobulinemia (based on the WHO definition of clonal lympho-plasmocytes ≥10%), marginal zone lymphoma, chronic lymphocytic leukemia or low- grade lymphoma not otherwise specified;\n- ● Presence of anti MAG antibodies (titer ≥ 7.000 BTU)"}

Exclusion criteria

• {"criterion_text":"- ● Previous treatment with BTK inhibitors\n- ● Aggressive non-Hodgkin lymphoma or IgM multiple myeloma\n- ● Evidence of moderate or severe motor nerve axonal damage\n- ● ECOG >3\n- ● Requiring ongoing therapy with strong or moderate cytochrome P450 3A (CYP3A) inducer. Use of strong/moderate CYP3A inducers within 14 days prior to the first dose of zanubrutinib (see Drug-interaction section).\n- ● creatinine clearance <30mL/min"}

Primary endpoints

• {"endpoint_text":"- The proportion of patients with neurological improvement defined as improvement of at least 1 point in at least 2 neurological scales (ONLS, INCAT disability, INCAT sensory sum scores (ISS), MRC sum score, I-RODS functional score) at 12 months of zanubrutinib treatment.","definition_or_measurement_approach":"Neurological improvement defined as improvement of at least 1 point in at least 2 neurological scales (ONLS, INCAT disability, INCAT sensory sum scores (ISS), MRC sum score, I-RODS functional score) measured at 12 months of treatment."}

Secondary endpoints

• {"endpoint_text":"- ● The proportion of patients with neurological improvement after 24 and 48 months of zanubrutinib;\n- ● the proportion of patients with ENG/EMG improvement since the baseline, assessing decrease of distal motor latency, increase of terminal latency index, increase of sensory nerve action potential amplitude (see criteria of evaluation) at upper limbs after zanubrutinib treatment at 12, 24 and 48 months;\n- ● levels of monoclonal protein, IgM and of anti-MAG antibody titers at 12, 24 and 48 months.","definition_or_measurement_approach":"Neurological improvement assessed at 24 and 48 months; ENG/EMG measures include decrease of distal motor latency, increase of terminal latency index, increase of sensory nerve action potential amplitude at upper limbs measured at 12, 24 and 48 months; laboratory measures of monoclonal protein, IgM and anti-MAG antibody titers at 12, 24 and 48 months."}

Other endpoints

• {"endpoint_text":"- To evaluate the quality of life or patients by FACT-GOG-NTX-13 QOL questionnaire;\n- To identify any correlation between neurologic response (assessed by the neurological scaled mentioned in the primary endpoint) and hematologic overall response (CR, VGPR, PR) at 24 and 48 months, event free survival, time to progression and overall survival with demographic, clinical and molecular features of the patients at baseline;\n- To evaluate the reduction of MYD88 mutational burden by cf-DNA during treatment;\n- To evaluate the emergence of BTK and PLCG2 mutational status in relapsing patients.","definition_or_measurement_approach":"Quality of life measured by FACT-GOG-NTX-13 questionnaire; correlative analyses between neurologic and hematologic responses and clinical/molecular baseline features at 24 and 48 months; serial cf-DNA assays to quantify MYD88 mutational burden during treatment; genotyping for BTK and PLCG2 mutations in relapsing patients."}

Italy

Earliest CTIS Part Ii Submission Date

17-11-2025

Latest Decision Or Authorization Date

03-04-2026

Processing Time Days

137

Number Of Sites

9

Number Of Participants

50

Primary sponsor

Full Name

Azienda Ospedaliera di Padova

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"EUROMED PHARMA","duties_or_roles":"VENDOR - labelling and distribution of the IMP (mentioned as 'EUROMED PHARMA (VENDOR - labelling and distribution of the IMP): Certificate no. IT/134/H/2025')","organisation_type":""}
• {"country":"","full_name":"BEIGENE","duties_or_roles":"Sponsor/manufacturer name listed for product Zanubrutinib (product dictionary: nameOrg 'BEIGENE')","organisation_type":""}
• {"country":"Ireland","full_name":"BEONE MEDICINES IRELAND LIMITED.","duties_or_roles":"Marketing authorisation holder for BRUKINSA 80 mg hard capsules (product dictionary nameOrg 'BEONE MEDICINES IRELAND LIMITED.')","organisation_type":""}