Evaluating Zanubrutinib with Bendamustine and Rituximab for Newly-diagnosed Waldenström's Macroglobulinemia

A Prospective, Open-label, Multicenter Study of Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia

This study is testing if a new combination of zanubrutinib with bendamustine and rituximab can help people who are newly diagnosed with Waldenström's macroglobulinemia achieve better results than using just one of the treatments alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (Academic / other)
• Drugs / interventions: chemotherapy, Rituximab, zanubrutinib
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05979948 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial assesses the effectiveness of zanubrutinib combined with the BR regimen (bendamustine and rituximab) in patients newly diagnosed with Waldenström's macroglobulinemia. The study involves a single-arm treatment approach where participants will receive the combination therapy over six 28-day cycles, followed by a follow-up phase to monitor treatment response. Key assessments will include disease evaluations through ultrasounds and laboratory tests to measure serum IgM and other relevant markers. The goal is to achieve deeper remission compared to using either treatment alone.

Who should consider this trial

Good fit: Ideal candidates are newly diagnosed patients with Waldenström's macroglobulinemia who meet treatment criteria and have not received prior treatment.

Not a fit: Patients with significant organ damage or those who have previously undergone treatment for Waldenström's macroglobulinemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could lead to improved remission rates and reduced lifetime therapy for patients with Waldenström's macroglobulinemia.

How similar studies have performed: While this approach is being evaluated in this specific context, similar combinations of therapies have shown promise in other studies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

Subjects must meet all of the following criteria to be enrolled:

1. Newly diagnosed patients with waldenström's macroglobulinemia meeting at least one criterion for treatment according to consensus panel criteria from the eleventh IWWM.
2. ECOG score: 0-3 points, estimated survival time exceeding 3 months.
3. Did not receive any treatment for Waldenström's macroglobulinemia before screening, except for glucocorticoid therapy for autoimmune hemolysis.
4. No serious damage to main organs, and meet the following laboratory examination indicators: creatinine clearance rate≥40ml/min, total bilirubin≤1.5 times of the upper limit of normal range; AST and ALT≤2.5 times of the upper limit of normal range; Myocardial enzyme≤2 times of the upper limit of normal range; ECHO must demonstrate left ventricular ejection fraction (LVEF) within the normal range, and no ECG abnormality with clinical significance.
5. Neutrophil count≥1.5×10\^9/L without growth factor therapy within 7 days before screening; Platelet count≥50×10\^9/L without growth factor support or transfusion within 7 days before screening; Hemoglobin≥60 g/L without erythropoietin (EPO) support or transfusion within within 7 days before screening.
6. No history of paroxysmal atrial fibrillation or chronic persistent atrial fibrillation.
7. Able to swallow and Oral administration.
8. The subjects complete all screening and evaluations listed in all trial protocols.
9. The subjects who signed the informed consent form for chemotherapy.

Exclusion Criteria:

1. Waldenström's macroglobulinemia with amyloidosis or POEM syndrome
2. HIV positive, or patients with active hepatitis A, hepatitis B, and hepatitis C infection; Or the number of copies of hepatitis B virus\>10\^2.
3. Accompanied by other serious unstable diseases, including heart failure, renal failure, liver failure, hemorrhagic diseases, uncontrollable diabetes, etc.
4. In the past two years, the terminal organ was damaged due to autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required.
5. Serious infectious diseases (uncured pulmonary tuberculosis, pulmonary aspergillosis, etc.).
6. Other uncontrolled malignancies (excluding non Melanoma skin cancer, cervical cancer in situ, bladder cancer cancer and breast cancer with disease-free survival of more than 5 years).
7. Individuals with epilepsy, dementia, and other mental disorders who require medication treatment and are unable to understand or follow the research protocol.
8. Drug use, medical, psychological, or social conditions that may interfere with participants' participation in the study or evaluation of the results.
9. Pregnant and lactating women.
10. Patients who are accounted to be not appropriate for this trail by investigator.

Where this trial is running

Shanghai, Shanghai

• Shanghai Changzheng Hospital — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Juan Du, Doctor — Shanghai Changzheng Hospital
• Study coordinator: Haiyan He, Master

Conditions Waldenström's Macroglobulinemia; Waldenström's macroglobulinemia; Zanubrutinib; BR regimen; newly-diagnosed