This study is a prospective phase II clinical trial designed to evaluate the deep response rate of the ZBR regimen (zanubrutinib combined with reduced-dose bendamustine and CD20 Monoclonal Antibody ) in treatment-naïve symptomatic Waldenström macroglobulinemia (WM) patients. Eligible patients will receive four cycles of the ZBR regimen, followed by zanubrutinib monotherapy for an additional eight months. The assessment period spans from the initiation of treatment until 12 months after treatment completion, with efficacy evaluations conducted every three cycles. Patients will be withdrawn from the study if they experience disease progression (PD) or show no response to treatment. Minimal residual disease (MRD) assessments will be performed at the end of the 3rd and 6th treatment cycles, as well as 12 months after treatment completion, involving evaluations of both bone marrow and peripheral blood MRD rates
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Patients in the experimental group will receive treatment in 4-week cycles, totaling 4 cycles of zanubrutinib + bendamustine + CD20 Monoclonal Antibody therapy, followed by 8 months of zanubrutinib monotherapy maintenance. Specific regimen: Zanubrutinib: Oral administration starts on Day 1 of Cycle 1 and continues continuously at 160 mg twice daily. Bendamustine: Intravenous infusion at 70 mg/m² on Days 1-2 of Cycles 1-4. CD20 Monoclonal Antibody: Intravenous infusion at 375 mg/m² on Day 0 of Cycles 1-4. After completing the 4-cycle combination therapy, a systematic efficacy evaluation will be conducted.
Patients will then continue with zanubrutinib monotherapy maintenance for 8 months before treatment discontinuation.
China Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
Tianjin, China, China
Institute of Hematology & Blood Diseases Hospital, China
Tianjin, Tianjin Municipality, China
Best deep response rate(≥VGPR)
defined as the rate of very good partial response VGPR or CR
Time frame: up to 1 year
MRD Negativity Rate at End of Treatment
MRD Negativity Rate at End of Treatment
Time frame: up to the end of treatment
Duration of Response
The length of time between the achievement of criteria for response to treatment (first documented complete or partial response) and the first documented relapse or progression.
Time frame: up to 3 years
Objective Response Rate (ORR)
Response Rate (ORR) is defined as the proportion of subjects who achieve CR ,VGPR, PR or MR at the end of Treatment
Time frame: up to 1 year
Complete Response (CR) Rate
To assess CR rate at the end of treatment
Time frame: up to 1 year
Major Response Rate (MRR, ≥ Partial Response)
Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR at the end of Treatment
Time frame: up to 1 year
Time to First Response
Time to First Observed Response During Treatment
Time frame: up to 1 year
Time to Best Response
Time to the Best Response
Time frame: up to the end of treatment
Progression-Free Survival (PFS)
The time from the enrollment of a subject to the occurrence of (in any way) progression of disease or Death for any reason. patients with indeterminate recurrence or Death at the last follow-up, defined as the date of the last Investigation
Time frame: up to 3 years
Overall Survival (OS) Rate
The time from subject enrollment to Death caused by any reason. for patients lost to follow-up, the time of the last follow-up; for patients still alive at the end of study, the date of the end of follow-up.
Time frame: up to 3 years
Time to Next Treatment (TTNT)
Time from the initiation of the current treatment regimen to the start of the next line of therapy
Time frame: up to 3 years
Treatment-Related Adverse Events (AEs)
Incidence of adverse events, serious adverse events and significant adverse event
Time frame: up to 3 years
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