Active — Not RecruitingPhase 2

Zanubrutinib Treatment in Patients With IgM Monoclonal Gammopathy and Antri-MAG Related Polyneuropathy

Netherlands35 participantsStarted 2024-03-01

Plain-language 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.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 \< 1.5× ULN and creatinine clearance ≥ 30 ml/min * Patients with hypertension can only be enrolled when blood pressure is adequately treated, defined as systolic blood pressure of \<140 mmHg and diastolic blood pressure of \<90 mmHg at screening * No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention * Previous treatment with intravenous immunoglobulins is all…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Proportion of patients with ≥2 points improvement on the INCAT disability score

Timeframe: At the end of Cycle 12 (each cycle is 28 days)

Incidence of adverse events during treatment and follow up by the Common Terminology Criteria for Adverse Events (CTCAE), version 5

Timeframe: Till 36 months from baseline

Study Drug adherence

Timeframe: Till end of treatment, which will be after 6 or 12 cycles (each cycle is 28 days)

Trial details

NCT IDNCT05939037

SponsorUMC Utrecht

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-12-31

View on ClinicalTrials.gov More Monoclonal Gammopathy of Uncertain Significance trials