Zanubrutinib Combined With BR in the First-line Treatment of Waldenström's Macroglobulinemia

NCT06942507 | Not Yet Recruiting DMC

• 1 other identifier: BRZ-WM
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Waldenström's Macroglobulinemia (WM)

Keywords

Rituximab; Zanubrutinib; MYD88; Waldenström's Macroglobulinemia; Bendamustine

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Complete Response (CR) at 4 to 6 Months After Treatment Initiation

  4 to 6 months after treatment initiation

Secondary Outcomes (6)

• 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

  4 to 6 months after treatment initiation

• Rate of Progression-Free Survival

  2 years

• Time to next treatment

  2 years

• Rate of Overall Survival

  2 years

Other Outcomes (1)

• Medical resource utilization

  4 to 6 months after treatment initiation

Study Arms (1)

BRZ

EXPERIMENTAL

participants recieve 4 to 6 cycles of the zanubrutinib-rituximab-bendamustine regimen

Drug: Zanubrutinib; Drug: Bendamustine + Rituximab

Interventions

Zanubrutinib DRUG

zanubrutinib 160mg po bid d1-28

BRZ

Bendamustine + Rituximab DRUG

bendamustine 70-90mg/m2 ivgtt d1-2, rituximab 375mg/m2 ivgtt d1

BRZ

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated symptomatic Waldenström macroglobulinemia (WM) meeting IWWM-7 diagnostic criteria:
• Presence of monoclonal IgM-type immunoglobulin in serum
• Bone marrow infiltration by plasmacytoid lymphocytes or bone marrow biopsy showing small lymphocytes/plasma cells/plasmacytoid lymphocytes (any quantity) in the intertrabecular space
• 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.
• MYD88 L265P mutation is detected in peripheral blood or bone marrow.
• Serum monoclonal IgM ≥5 g/L.

You may not qualify if:

• Co-morbidity of uncontrolled infection or autoimmune disease
• Co-morbidity of other active malignancy
• Co-morbidity of uncontrolled heart disease
• Co-morbidity of severe digestive system disorders precluding oral medication
• Seropositive for human immunodeficiency virus
• Hepatitis B virus (HBV)-DNA \> 1000 copies/mL
• Seropositive for hepatitis C (except in the setting of a sustained virologic response)
• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, China

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

zanubrutinib; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Jian Li

CONTACT

86+18610852525; lijian@pumch.cn

Jia Chen

CONTACT

86+18813002022; chenjiapumc@yeah.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 17, 2025
• First Posted: April 24, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2029
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)