Zanubrutinib for anti‑MAG IgM‑associated demyelinating neuropathy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

The MAZINGA trial is a multicenter, open‑label, single‑arm Phase IIA study testing oral zanubrutinib given for 12 months in adults with IgM anti‑myelin‑associated glycoprotein (anti‑MAG) demyelinating polyneuropathy. The primary outcome is clinical neurological improvement, defined as at least a one‑point improvement in two or more validated scales such as the Overall Neuropathy Limitations Scale (ONLS), INCAT Disability Score, and INCAT Sensory Sum Score. Participants must have neurophysiological evidence of demyelination and an underlying IgM monoclonal gammopathy with anti‑MAG titers ≥7,000 BTU, and patients with prior BTK inhibitor use or significant axonal damage are excluded. Safety, tolerability, and secondary clinical and electrophysiological measures will be monitored throughout the treatment period.

Why it matters

Who can join: the full rules

Inclusion Criteria (MAIN):

* age ≥18 years;
* diagnosis of anti-MAG antibody polyneuropathy;
* neurophysiological (ENG/EMG) evidence of a demyelinating polyneuropathy with evidence of disproportionately prolonged distal motor latency in one or more nerves -excluding the median nerve if related to carpal tunnel syndrome
* IgM monoclonal protein underlying MGUS (based on the WHO definition of clonal lympho- plasmocytes \<10%), 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;
* presence of anti MAG antibodies (titer ≥ 7.000 BTU);
* neurophysiological (ENG/EMG) evidence of demyelinating polyneuropathy.

Exclusion Criteria (MAIN):

* Previous treatment with BTK inhibitors
* Aggressive non-Hodgkin lymphoma or IgM multiple myeloma
* Evidence of moderate or severe motor nerve axonal damage, defined when occurring diffuse polyneuropathic denervation or a recruitment pattern lower than intermediate in ≥50% of muscles examined, and/or INCAT at lower limbs ≥4.
* ECOG \>3
* Use of strong CYP3A inducers within 14 days prior to the first dose of zanubrutinib

Where it's running

• Neuroimmunology and neuromuscular disease unit, IRCCS Ospedale Clinico Humanitas di Rozzano, Milano
  Milan, Milan, Italy Recruiting
• CTU Ematologia, Grande Ospedale Metropolitano Niguarda
  Milan, Milan, Italy Recruiting
• UOC Ematologia, Azienda Ospedale Università Padova
  Padova, Pd, Italy Recruiting
• SC Ematologia 1 - Fondazione IRCCS Policlinico San Matteo
  Pavia, Pv, Italy Recruiting
• UOSD Leucemia Linfatica Cronica, Fondazione Policlinico Universitario "A. Gemelli", IRCCS
  Roma, Rm, Italy Recruiting
• SC Ematologia U, Ospedale Molinette, Torino (TO)
  Torino, To, Italy Recruiting

Study contacts

• Study coordinator: Andrea Visentin, Dr, Medical Doctor
• Email: ANDREA.VISENTIN@UNIPD.IT
• Phone: +39 049 821 2298

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.