Study on Zanubrutinib for Patients with Primary Cold Agglutinin Disease

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What is this study about?

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.

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 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 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 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 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 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 Study?

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 Study?

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.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Katholieke Universiteit te Leuven	Leuven	Belgium
Oslo Universitetssykehus HF	Oslo	Norway

Other Sites

Site Name	City	Country
St. Olavs Hospital HF	Trondheim	Norway
Odense University Hospital	Odense	Denmark
Rigshospitalet	Copenhagen	Denmark
Algemeen Ziekenhuis Delta	Roeselare	Belgium
Ujojshcmudew Mqendrb Cxkqmuf Gntzajcjo	Groningen	The Netherlands
Aanlogxfq Ujk	Amsterdam	The Netherlands
Eowxshg Ugwwpfccchal Mqlhntm Cluslvp Rbtkkgsvq (shucwea Mro	Rotterdam	The Netherlands

Trial status

Country	Status	Recruitment Start
Belgium	Not recruiting	01.01.2024
Denmark	Not recruiting	01.01.2024
Norway	Not recruiting	01.01.2024
The Netherlands	Not recruiting	01.01.2024

Trial locations

Investigated drugs:

Zanubrutinib

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.

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 ID:

2023-505746-25-00

Protocol code:

HOVON 169

NCT ID:

NCT06067048

Trial Phase:

Therapeutic exploratory (Phase II)

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