Ongoing Clinical Trials for Waldenstrom’s Macroglobulinaemia Refractory
There are currently 2 clinical trials underway for patients with Waldenstrom’s macroglobulinaemia that has not responded to previous treatments or has returned after treatment. These trials are testing new combinations of medications designed to target cancer cells through different mechanisms, including BCL2 inhibitors and BTK inhibitors. The studies are being conducted across several European countries including France, Germany, Greece, Italy, Poland, and Spain.
Clinical trial locations
- France
- Germany
- Greece
- Italy
- Poland
- Spain
Evaluating Sonrotoclax Alone and Combined with Zanubrutinib for Patients with Previously Untreated or Relapsed/Refractory Waldenström Macroglobulinemia
This trial is testing two medications, sonrotoclax and zanubrutinib, either alone or in combination. The study is examining how effective and safe these treatments are for patients at different stages of disease.
Who can participate:
You may be eligible for this trial if you are at least 18 years old and have a confirmed diagnosis of Waldenstrom’s macroglobulinaemia that meets criteria for treatment. The trial has four different groups of patients:
- Patients whose disease has returned or not responded after treatment with both a BTK inhibitor and anti-CD20 antibody therapy
- Patients who could not tolerate BTK inhibitor treatment and whose disease progressed after anti-CD20 antibody therapy
- Patients whose disease progressed after BTK inhibitor treatment and who are not suitable for chemotherapy combined with immunotherapy
- Newly diagnosed patients who have not yet received any treatment
You must have adequate organ function to participate. For previously treated patients, your disease must have either not responded to previous treatment, progressed during treatment or within 6 months after completing it, or progressed more than 6 months after completing therapy.
Who cannot participate:
The exclusion criteria vary depending on which patient group you would be in. Generally, patients in the relapsed or refractory groups must have previously been treated with and had their disease progress after certain medications, including BTK inhibitors and anti-CD20 antibody therapy combined with chemotherapy or proteasome inhibitors.
What the trial aims to achieve:
The main goal is to evaluate whether these medications, used alone or together, are effective and safe for treating this condition. Researchers will track how well patients respond to treatment by measuring changes in the cancer, monitoring side effects through laboratory tests, and assessing how the treatment affects quality of life and disease symptoms. The study will measure various outcomes including how many patients respond, how long responses last, progression-free survival, and overall survival.
Medications being tested:
The trial is studying two investigational drugs. Sonrotoclax (also known as BGB-11417) is a BCL2 inhibitor that works by blocking a protein that helps cancer cells survive, potentially causing them to die. Zanubrutinib (BGB-3111) is a Bruton tyrosine kinase inhibitor that blocks signals helping cancer cells grow. Both medications are taken by mouth as capsules or tablets.
Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
This clinical trial is investigating different combinations of medications for B-cell blood cancers that have returned or not responded to previous treatments. The study will test multiple drug combinations to find safe and effective options.
Who can participate:
You may be eligible if you are at least 18 years old with a confirmed diagnosis of relapsed or refractory B-cell malignancy. You must have disease that can be measured according to the study protocol and be able to perform daily activities with minimal limitations. Adequate organ and kidney function is required, though the specific kidney function requirements vary between different parts of the study.
Women who can become pregnant must use effective birth control during the study and have a negative pregnancy test before starting treatment. Men who are not sterile must also use birth control and agree not to donate sperm during and for a specified time after treatment.
Who cannot participate:
You cannot participate if you are under 18 years old, have active cancer involvement in the central nervous system, or have received similar therapy or participated in another clinical trial within 30 days. Other exclusions include active uncontrolled infections, significant heart problems, severe kidney or liver problems, pregnancy or breastfeeding, history of other cancers within the past 3 years (with certain exceptions), known HIV infection, active hepatitis B or C, major surgery within 4 weeks, mental conditions that could interfere with participation, allergic reactions to similar medications, uncontrolled high blood pressure, or any serious medical condition that could make participation unsafe.
What the trial aims to achieve:
The study is conducted in two parts. The first part will determine the appropriate dose of the drug combinations, while the second part will further evaluate how well these doses work and what side effects they may cause. Researchers will monitor patients’ health throughout, checking treatment effectiveness and tracking side effects. They will measure how many patients respond to treatment and how long the response lasts. For some patients, the amount of cancer cells remaining in blood or bone marrow after treatment will also be measured.
Medications being tested:
The main medication being studied is BGB-16673, an experimental BTK-degrader that works by breaking down a specific protein important in B-cell cancers. This medication is taken as tablets by mouth. Depending on your assigned treatment group, you may also receive other medications including obinutuzumab (Gazyvaro) through intravenous infusion, zanubrutinib as oral capsules, glofitamab (Columvi) through intravenous infusion, or mosunetuzumab as an injection under the skin.
Summary
The two ongoing clinical trials for refractory Waldenstrom’s macroglobulinaemia represent different approaches to treating this challenging condition. Both trials focus on targeting specific proteins involved in cancer cell survival and growth, using BTK inhibitors and related mechanisms.
The trials are concentrated in European countries, with Italy hosting both studies, while France, Greece, and Spain participate in the first trial, and Germany and Poland participate in the second. Both studies include patients whose disease has not responded to previous treatments, though the first trial also includes a group for newly diagnosed patients who have not yet received any treatment.
A notable feature is that both trials are testing combinations of medications rather than single drugs, reflecting the current approach of using multiple mechanisms to target cancer cells. The medications are administered in various ways, including oral tablets and intravenous infusions, allowing flexibility in treatment delivery. These trials are still in progress, and participation requires meeting specific eligibility criteria and being able to attend regular monitoring visits.
