Waldenström's Macroglobulinemia (WM)
Conditions
Keywords
Rituximab, Zanubrutinib, MYD88, Waldenström's Macroglobulinemia, Bendamustine
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.
Interventions
DRUGZanubrutinib
zanubrutinib 160mg po bid d1-28
bendamustine 70-90mg/m2 ivgtt d1-2, rituximab 375mg/m2 ivgtt d1
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | 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 | 4 to 6 months after treatment initiation | CR + VGPR + partial response (PR) |
| Time to next treatment | 2 years | — |
| Rate of Overall Survival | 2 years | — |
| Rate of Progression-Free Survival | 2 years | — |
Other
| Measure | Time frame |
|---|---|
| Medical resource utilization | 4 to 6 months after treatment initiation |
Countries
China
Contacts
Primary ContactJian Li
Backup ContactJia Chen
Outcome results
None listed