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Study on Zanubrutinib for Patients with Primary Cold Agglutinin Disease

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a condition known as Cold Agglutinin Disease (CAD). CAD is a rare blood disorder where the immune system mistakenly attacks and destroys red blood cells, especially in cold temperatures. The trial will investigate the effects of a medication called Zanubrutinib, which is a type of drug known as a tyrosine kinase inhibitor. This medication is taken orally in the form of a capsule.

The purpose of the study is to evaluate how effective Zanubrutinib is in treating patients with primary CAD. Participants in the study will receive Zanubrutinib over a series of 6 treatment cycles. During these cycles, the response of the disease to the medication will be closely monitored. The study aims to see if Zanubrutinib can help reduce the symptoms of CAD and improve the overall health of the participants.

Throughout the study, various aspects of the participants' health will be assessed, including changes in blood parameters and symptoms related to CAD. The study will also look at how the treatment affects the quality of life and fatigue levels of the participants. The trial is designed to provide valuable information on the potential benefits of Zanubrutinib for individuals living with CAD.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Joining the study

    Upon joining the study, the patient will begin participation in a clinical trial focused on evaluating the effectiveness of zanubrutinib for treating primary cold agglutinin disease (CAD).

  2. Step 2

    Treatment initiation

    The patient will start taking zanubrutinib, which is administered orally in the form of a capsule.

    The treatment consists of 6 cycles, with each cycle lasting 28 days.

  3. Step 3

    Treatment administration

    During each cycle, the patient will take zanubrutinib as prescribed by the study protocol.

    The dosage and frequency of administration will be determined by the study guidelines and the patient's specific condition.

  4. Step 4

    Monitoring and assessment

    Throughout the treatment, the patient's response to zanubrutinib will be closely monitored.

    Assessments will be conducted to evaluate the response rate of CAD, including partial response (PR) or complete response (CR) after 6 cycles.

  5. Step 5

    End of cycle evaluation

    At the end of cycle 6, between days 22 and 28, the primary outcome will be assessed before starting cycle 7.

    This evaluation will determine the effectiveness of the treatment in managing CAD symptoms and improving the patient's condition.

  6. Step 6

    Secondary assessments

    Additional assessments will be conducted to measure various outcomes, such as changes in hemolytic parameters, improvement in cold-induced symptoms, and overall survival rates.

    The impact of zanubrutinib on quality of life and fatigue will also be evaluated through patient-reported outcomes.

Who can join the trial?

18 criteria

  • Must have a diagnosis of **Cold Agglutinin Disease (CAD)**, which includes:
    • Chronic hemolysis (breakdown of red blood cells) for more than 3 months with low haptoglobin levels.
    • Cold agglutinin titer of 64 or higher at 4°C.
    • Positive direct antiglobulin test, strongly positive with anti-C3d and negative or weakly positive with anti-IgG.
    • Presence of a clonal B-cell lymphoproliferative disorder, which means:
      • M-protein detected by serum electrophoresis confirmed by immunofixation.
      • A clonal CD20 positive lymphocyte population in the bone marrow, even if very small.
      • Must provide written informed consent and be able to understand and agree to the study requirements.
      • Must need therapy due to:
        • Hemoglobin level of 10.5 g/dL or lower.
        • Significant cold-induced symptoms.
        • Must have either relapsed or not responded to at least one previous CAD treatment, or be new to treatment and not eligible for current options.
        • Must be 18 years of age or older.
        • Must have an **ECOG/WHO performance status** of 2 or lower, or 3 if related to CAD. This is a measure of daily living abilities.
        • Must have adequate bone marrow function, meaning:
          • Absolute neutrophil count (ANC) greater than 1.0 x 109/L.
          • Platelet count of 100 x 109/L or higher.
          • Must have ferritin levels above the lower limit of normal, with stable iron supplementation if needed.
          • Must have a total bilirubin level above the upper limit of normal, not due to Gilbert's syndrome, as a measure of hemolysis.
          • Women of childbearing potential must have a negative pregnancy test at study entry.
          • Women of childbearing potential must be surgically sterile, post-menopausal for at least 2 years, or willing to use effective contraception during and after the study.
          • Male patients with a female partner of childbearing potential must be vasectomized or agree to use barrier contraception during and after the study.

Who cannot join the trial?

8 criteria

  • Patients who have other serious health conditions that might interfere with the study.
  • Patients who are currently participating in another clinical trial.
  • Patients who have had a recent major surgery or are planning to have one during the study period.
  • Patients who are pregnant or breastfeeding.
  • Patients who have a history of allergic reactions to similar medications.
  • Patients who have an active infection that requires treatment.
  • Patients who have a history of drug or alcohol abuse.
  • Patients who are unable to follow the study procedures or attend the required visits.
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Investigated drugs

Zanubrutinib is a medication being studied for its effectiveness in treating primary Cold Agglutinin Disease (CAD). It is designed to help manage the symptoms of CAD by targeting specific pathways in the immune system that contribute to the disease. The trial aims to assess how well zanubrutinib works over a series of treatment cycles.

What is already known about the treatment

Zanubrutinib – Zanubrutinib is administered orally in the form of capsules. It is currently being studied in clinical trials for its effectiveness in treating primary Cold Agglutinin Disease (CAD). The main therapeutic indication for zanubrutinib is to manage symptoms and improve the condition of patients with CAD. At the molecular level, zanubrutinib works by inhibiting Bruton's tyrosine kinase (BTK), which plays a crucial role in the signaling pathways that lead to the production of antibodies that can cause red blood cells to clump together. It is classified as a Bruton's tyrosine kinase inhibitor in pharmacology.

Investigated diseases

Cold agglutinin disease – Cold agglutinin disease is a rare autoimmune disorder where the immune system mistakenly attacks and destroys red blood cells at low temperatures. This leads to the clumping of red blood cells, causing them to break down prematurely. The disease often results in symptoms such as fatigue, weakness, and pale skin due to anemia. Patients may also experience cold-induced symptoms like numbness or pain in extremities. The condition can be chronic, with symptoms worsening in cold environments. It is important to manage exposure to cold to help reduce symptoms.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IITrial ID2023-505746-25-00Protocol codeHOVON 169Estimated enrolment26 patientsSponsorHemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

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On this site, “treatment” means an investigational medicine being studied in a clinical trial. Its safety and efficacy for the use being studied have not yet been confirmed, some participants may receive a placebo or a comparator medicine, and taking part does not guarantee any health benefit. The decision to take part is made by the doctor at the research site. This site is for information only and does not replace medical advice.

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