Evaluating Sonrotoclax Alone and Combined with Zanubrutinib for Patients with Previously Untreated or Relapsed/Refractory Waldenström Macroglobulinemia

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What is this study about?

This clinical trial is studying Waldenström Macroglobulinemia, a rare type of blood cancer where the bone marrow produces too many abnormal white blood cells. The study will evaluate two medications: sonrotoclax (also known as BGB-11417), which is a BCL2 inhibitor that helps trigger cancer cell death, and zanubrutinib (BGB-3111), which is a Bruton tyrosine kinase (BTK) inhibitor that blocks signals that help cancer cells grow. The purpose is to assess how effective and safe these medications are when used alone or in combination for treating patients with this disease.

The study includes different groups of patients: those whose disease has returned or not responded to previous treatments (relapsed/refractory disease), those who couldn’t tolerate certain previous treatments, and those who haven’t received any treatment yet for their Waldenström Macroglobulinemia. During the study, participants will receive either sonrotoclax alone or in combination with zanubrutinib, depending on which study group they join.

Researchers will track how well patients respond to the treatment by measuring changes in their cancer. They will also monitor side effects, laboratory test results, and how the treatment affects patients’ quality of life and symptoms related to their disease.

1 Screening Period

You will undergo medical evaluations to confirm your eligibility for the study. This includes confirming your diagnosis of Waldenström Macroglobulinemia (WM), a rare type of blood cancer, and verifying that you meet all other criteria for your specific study cohort.

Depending on which cohort you’re assigned to, you may need to have previous treatment history with specific medications or have certain disease characteristics.

2 Assignment to Study Cohort

Based on your medical history, you will be assigned to one of four cohorts:

Cohort 1: If your WM has returned or not responded adequately after both BTK inhibitor therapy and anti-CD20 antibody-based therapy.

Cohort 2: If you couldn’t tolerate BTK inhibitor therapy and have had anti-CD20 antibody-based therapy that didn’t work well enough.

Cohort 3: If your disease progressed after BTK inhibitor therapy and you’re not suitable for chemotherapy combined with immunotherapy.

Cohort 4: If you haven’t received any prior therapy for WM (newly diagnosed patients).

3 Treatment Phase

You will receive treatment with Sonrotoclax (BGB-11417), either alone or in combination with Zanubrutinib (BGB-3111).

Zanubrutinib is taken as capsules or film-coated tablets.

The exact dosage, schedule, and whether you receive one or both medications will depend on your assigned cohort.

Treatment will continue until your disease progresses, you experience unacceptable side effects, or you decide to withdraw from the study.

4 Regular Monitoring Visits

Throughout the treatment period, you will have regular clinic visits for monitoring.

These visits will include blood tests to check your blood cell counts and assess how your WM is responding to treatment.

You’ll undergo physical examinations and assessments of any side effects you might be experiencing.

The study team will monitor the function of your organs through laboratory tests.

You’ll complete questionnaires about your quality of life and any symptoms you’re experiencing (using the NFLymSI-18 assessment).

5 Response Assessment

Your response to treatment will be evaluated regularly according to established criteria for WM (IWWM-11 response criteria).

These assessments will determine if you’re having a complete response (CR), very good partial response (VGPR), partial response (PR), minor response (MR), or if the disease is stable or progressing.

Some of these assessments will be done by your study doctor, while others will also be reviewed by an Independent Review Committee.

6 End of Treatment

Treatment will end if your disease progresses, you experience unacceptable side effects, you decide to withdraw from the study, or the study reaches its conclusion.

At the end of treatment, you’ll have a final evaluation to assess your overall health and the status of your WM.

7 Follow-up Period

After completing treatment, you’ll enter the follow-up phase.

You’ll have periodic assessments to monitor for long-term effects of the treatment and to track how long your response lasts.

The study will track important outcomes such as progression-free survival (how long until your disease worsens) and overall survival.

For newly diagnosed patients (Cohort 4), the study will also track how long until you need your next treatment for WM.

Who Can Join the Study?

You must be 18 years or older
You must have a confirmed diagnosis of Waldenström’s Macroglobulinemia (a rare type of blood cancer)
You must meet at least one criterion for needing treatment according to established guidelines
You must have adequate organ function
For patients with previously treated disease (Cohorts 1-3), you must have either:
- Disease that did not respond to previous treatment (did not achieve at least a minimal response), or
- Disease that progressed during treatment or within 6 months after completing therapy, or
- Disease that initially responded but later progressed more than 6 months after completing therapy
For Cohort 1: You must have disease that progressed after treatment with both a BTK inhibitor (a type of targeted therapy) and anti-CD20 antibody-based therapy with chemotherapy or proteasome inhibitor
For Cohort 2: You must be unable to tolerate a BTK inhibitor despite supportive care measures, and have disease that progressed after anti-CD20 antibody-based therapy
For Cohort 3: You must have disease that progressed after BTK inhibitor treatment and be considered unsuitable for chemoimmunotherapy
For Cohort 4: You must not have received any prior therapy for Waldenström’s Macroglobulinemia (except for plasmapheresis, a procedure that filters the blood)

Who Cannot Join the Study?

You cannot participate if you have never been treated for Waldenström’s Macroglobulinemia (a type of blood cancer) before.
You cannot participate if your disease has not previously been treated with and relapsed or become resistant to a BTK inhibitor (a type of medication that blocks an enzyme called Bruton’s tyrosine kinase).
You cannot participate if your disease has not previously been treated with and relapsed or become resistant to anti-CD20 antibody therapy (a treatment that targets a specific protein on cancer cells) combined with chemotherapy or a proteasome inhibitor (a medication that blocks protein breakdown in cells).
You must have relapsed or refractory disease, which means your cancer has returned after treatment or did not respond adequately to previous treatments.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Hospital Universitario De Salamanca	Salamanca	Spain
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
University Hospital Of Clermont-Ferrand	Clermont Ferrand	France

Other Sites

Site Name	City	Country
ASST Grande Ospedale Metropolitano Niguarda	Milan	Italy
Fondazione IRCCS Policlinico San Matteo	Pavia	Italy
Alexandra Hospital	Athens	Greece
Hospital Universitario Fundacion Jimenez Diaz	Madrid	Spain
Fundacio Assistencial De Mutua De Terrassa Fpc	Terrassa	Spain
Centre Hospitalier Universitaire Amiens Picardie	Amiens	France
Hopitaux Universitaires Pitie Salpetriere	Paris	France
Virgen del Rocío University Hospital	Sevilla	Spain
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer	Barcelona	Spain
Azienda Sanitaria Universitaria Friuli Centrale	Udine	Italy
Centre Hospitalier Lyon Sud	Pierre Benite	France
Universita Degli Studi Di Brescia	Brescia	Italy
Agigwfy Usxij Sgjwzgslr Loeaan Dt Bdackls	Bologna	Italy
Ctbevz Hdgmzgiogmq Ueemczuivfszm Rlnho	Reims	France
Ilgnxblh Cmpisr Dqnjbgvklwsdisrbd	L'hospitalet De Llobregat	Spain
Hewsycoi Vvoi dstldvpw	Barcelona	Spain
Ijyxfykv Pusrdfoybnqhiul Caqxap Cuhjkd	Marseille	France

Trial status

Country	Status	Recruitment Start
France	Not recruiting	01.03.2024
Greece	Not recruiting	01.03.2024
Italy	Not recruiting	01.03.2024
Spain	Not recruiting	01.03.2024

Trial locations

Investigated drugs:

Sonrotoclax (BGB 11417) is a BCL2 inhibitor. BCL2 is a protein that helps cancer cells survive by preventing them from dying naturally. This medication works by blocking BCL2, which may cause cancer cells to die. In this trial, it’s being studied for treating Waldenström macroglobulinemia, a type of blood cancer.

Zanubrutinib (BGB-3111) is a Bruton tyrosine kinase (BTK) inhibitor. BTK is an enzyme that plays an important role in the development and function of certain blood cells, including the cancerous cells in Waldenström macroglobulinemia. By blocking BTK, zanubrutinib may help slow down or stop the growth of these cancer cells.

Investigated diseases:

Waldenström’s Macroglobulinemia (WM) – A rare type of blood cancer where abnormal white blood cells called lymphoplasmacytic cells produce excessive amounts of a protein called macroglobulin. These cells grow primarily in the bone marrow, interfering with the production of normal blood cells. As the disease progresses, the abnormal cells may infiltrate the liver, spleen, and lymph nodes, causing them to enlarge. The excess protein in the blood can lead to hyperviscosity syndrome, where blood becomes too thick to flow properly. WM typically develops slowly, with symptoms including fatigue, unexplained weight loss, bleeding from the nose or gums, and visual problems.

Trial ID:

2023-503235-18-00

Protocol code:

BGB-11417-203

NCT ID:

NCT05952037

Trial Phase:

Therapeutic exploratory (Phase II)

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Evaluating Sonrotoclax Alone and Combined with Zanubrutinib for Patients with Previously Untreated or Relapsed/Refractory Waldenström Macroglobulinemia

What is this study about?

Who Can Join the Study?

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