Clinical trial NCT06942507: Zanubrutinib Combined With BR in the First-line Treatment of Waldenström's Macroglobulinemia
Official title: A Multicenter Study on the First-line Treatment of Waldenström's Macroglobulinemia With Zanubrutinib in Combination With Rituximab and Bendamustine
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Waldenström's Macroglobulinemia (WM)
Keywords: Rituximab
Zanubrutinib
MYD88
Waldenström's Macroglobulinemia
Bendamustine
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2025-04-24
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Achieving Complete Response (CR) at 4 to 6 Months After Treatment Initiation
timeFrame: 4 to 6 months after treatment initiation
Secondary outcomes:
measure: Number of Participants Achieving Very Good Partial Response (VGPR) at 4 to 6 Months After Treatment Initiation
timeFrame: 4 to 6 months after treatment initiation
measure: Number of Participants Achieving Overall Response (OR) at 4 to 6 Months After Treatment Initiation
timeFrame: 4 to 6 months after treatment initiation
measure: Rate of Progression-Free Survival
timeFrame: 2 years
measure: Time to next treatment
timeFrame: 2 years
measure: Rate of Overall Survival
timeFrame: 2 years
measure: Duration of response
timeFrame: 2 years
Other outcomes:
measure: Medical resource utilization
timeFrame: 4 to 6 months after treatment initiation
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
References: