Zanubrutinib Combined With BR in the First-line Treatment of Waldenström's Macroglobulinemia (BRZ-WM)

A Multicenter Study on the First-line Treatment of Waldenström's Macroglobulinemia With Zanubrutinib in Combination With Rituximab and Bendamustine

Current retrospective studies have demonstrated that achieving deep remission following treatment for Waldenström's macroglobulinemia (WM) correlates with prolonged survival. While the bendamustine-rituximab (BR) regimen or single-agent zanubrutinib are currently recommended as first-line therapies, neither achieves optimal deep remission. Additionally, prolonged zanubrutinib monotherapy may lead to cumulative adverse effects. Therefore, this study aims to evaluate the efficacy and safety of the bendamustine-rituximab-zanubrutinib combination regimen as a first-line treatment option for MYD88-mutated WM patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Waldenström's Macroglobulinemia (WM)
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Bendamustine + Rituximab

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jian Li; Phone Number: 86+18610852525; Email: lijian@pumch.cn
• Study Contact Backup: Name: Jia Chen; Phone Number: 86+18813002022; Email: chenjiapumc@yeah.net

Study Locations

• China
  • Beijing, China
    • Peking Union Medical College Hospital
    • Contact: Jiayue Li; Phone Number: 86+01069156874; Email: lijiayue@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Previously untreated symptomatic Waldenström macroglobulinemia (WM) meeting IWWM-7 diagnostic criteria:

   1. Presence of monoclonal IgM-type immunoglobulin in serum
   2. Bone marrow infiltration by plasmacytoid lymphocytes or bone marrow biopsy showing small lymphocytes/plasma cells/plasmacytoid lymphocytes (any quantity) in the intertrabecular space
   3. Exclusion of other non-Hodgkin lymphoma subtypes
   4. Typical immunophenotype: CD5-/CD10-/CD19⁺/CD20⁺/CD23-/CD79b⁺ /sIgM⁺/CD138- clonal B-cells. Variant phenotypes may show CD5/CD10/CD23 /CD38 positivity or coexistence of clonal B-cells and plasma cells.
2. MYD88 L265P mutation is detected in peripheral blood or bone marrow.
3. Serum monoclonal IgM ≥5 g/L.

Exclusion Criteria:

1. Co-morbidity of uncontrolled infection or autoimmune disease
2. Co-morbidity of other active malignancy
3. Co-morbidity of uncontrolled heart disease
4. Co-morbidity of severe digestive system disorders precluding oral medication
5. Seropositive for human immunodeficiency virus
6. Hepatitis B virus (HBV)-DNA > 1000 copies/mL
7. Seropositive for hepatitis C (except in the setting of a sustained virologic response)
8. Neutrophil <1×10E9/L, platelet < 75×10E9/L, alanine transaminase (ALT) or aspertate aminotransferase (AST) > 2.5 × upper limit of normal (ULN), total bilirubin > 1.5 × ULN，eGFR < 30 mL/min, or receiving renal replacement therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BRZ; participants recieve 4 to 6 cycles of the zanubrutinib-rituximab-bendamustine regimen	Drug: Zanubrutinib; zanubrutinib 160mg po bid d1-28; Drug: Bendamustine + Rituximab; bendamustine 70-90mg/m2 ivgtt d1-2, rituximab 375mg/m2 ivgtt d1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Achieving Complete Response (CR) at 4 to 6 Months After Treatment Initiation	4 to 6 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response		2 years
Time to next treatment		2 years
Number of Participants Achieving Very Good Partial Response (VGPR) at 4 to 6 Months After Treatment Initiation		4 to 6 months after treatment initiation
Number of Participants Achieving Overall Response (OR) at 4 to 6 Months After Treatment Initiation	CR + VGPR + partial response (PR)	4 to 6 months after treatment initiation
Rate of Progression-Free Survival		2 years
Rate of Overall Survival		2 years

Other Outcome Measures

Outcome Measure	Time Frame
Medical resource utilization	4 to 6 months after treatment initiation

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: April 17, 2025
• First Submitted That Met QC Criteria: April 17, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Rituximab; Bendamustine; Zanubrutinib; Waldenström's Macroglobulinemia; MYD88
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Waldenstrom Macroglobulinemia; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Bendamustine Hydrochloride; Rituximab; Zanubrutinib
• Other Study ID Numbers: BRZ-WM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No