Zanubrutinib Treatment in Patients With IgM Monoclonal Gammopathy and Antri-MAG Related Polyneuropathy
Trial Parameters
Brief Summary
The objective of this investigator-initiated phase II single-arm open-label clinical trial is to investigate neurological response rate, safety and tolerability of Zanubrutinib 320 mg daily in combination with Rituximab 375 mg/m2 (standard therapy) for the treatment of immunoglobulin M monoclonal gammopathy of unknown significance (IgM MGUS) related polyneuropathy with Myelin Associated Glycoprotein antibodies (anti-MAG). 42 adult patients will be included in two Dutch hospitals (University Medical Center Utrecht and Amsterdam University Medical Center). This trial consists of a 6-month treatment period, after which the hematological response will be evaluated. Adequately responding participants (at least partial response) will be treated for an additional 6 months, after which hematological response will be re-evaluated. Participants with at least a very good partial response will remain on treatment. Non-responding participants will be followed for clinical outcomes only. The total study period per participant will be 36 months.
Eligibility Criteria
Inclusion Criteria: * Able to provide written informed consent and understand and comply with the requirements of the study * Demyelinating PNP defined by the European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of paraproteinemic demyelinating neuropathies (84) * Functional impairment; defined as an INCAT disability score (INCATds) of ≥2 * Age ≥ 18 years * IgM MGUS, defined as the presence of an IgM M-protein (detectable but \< 30 g/L) AND elevated total IgM level in serum * Presence of anti MAG antibodies ≥ 10.000 titer units, measured with the Bühlmann ELISA * Eastern Cooperative Oncology Group (ECOG) performance score 0, 1, or 2 (85) * Adequate hematological laboratory values defined as hemoglobin ≥ 6.0 mmol/L, neutrophils \> 1.0 × 109/L and platelets \> 100 × 109/L * Adequate hepatic and renal function laboratory values defined as aspartate transaminase (ASAT)/ alanine aminotransferase (ALAT) \< 3 × upper limit of normal (ULN), bilirubin \