This was a single-arm, multicenter, Phase 2 study to evaluate the efficacy of zanubrutinib combined with BR (Bendamustine/Rituximab) regimen in Chinese participants with newly-diagnosed Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment based on consensus guidelines from the 11th International Workshop on Waldenström's Macroglobulinemia (IWWM). The investigators propose this combination will improve the deep remission compared to single Zanubrutinib or BR regimen and can be a time-limited regimen which will reduce the life-time therapy and benefit the patients.
The study comprised an initial screening phase (up to 7 days), a single-arm treatment phase, and a follow-up phase. Subjects with newly-diagnosed Waldenström's macroglobulinemia can participate if all eligibility criteria are met. The participants will receive bendamustine and rituximab for 6 28-day cycles. Bendamustine will be given intravenously at 70-90 mg/m2 on days 1 and 2 of each cycle. Rituximab will be given on day 1 of each cycle (375 mg/m2 intravenously), Zanubrutinib will be given orally 160mg Bid per day, up to 12 months. The participants with WM will also have disease assessment with Lymph node ultrasound and abdominal ultrasound each cource, serum IgM, serum protein electrophoresis (SPE), immunofixation (IFA), and viscosity assessments will be measured serially. A bone marrow aspiration and biopsy flow cytometry examination will be done before treatment and at response assessment at cycle 6 and 12. Durability of response will also be assessed every 3 months after treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Zanubrutinib, 160 mg oral capsules twice daily for 12 months
Bendamustine, 70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles.
Rituximab, 375 mg/m2 intravenously on day 0 of each cycle for 6 cycles
Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGOverall Response Rate (ORR)
ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response
Time frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
The best deep response rate
defined as complete response (CR) and very good partial response (VGPR)
Time frame: Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
Progression-free Survival (PFS)
PFS was defined as from the initiation of treatmentuntil to first documentation of progression or death, whichever comes first.
Time frame: Up to 6 years post first dose
Overall Survival (OS)
OS is measured from the date of the initial of treatment to the date of the subject's death.
Time frame: Up to 6 years post first dose
minimal residual disease (MRD) rate
MRD will be assessed at two on treatment timepoints (before start of cycles 7, 12) and every 6 months thereafter. MRD will be measured through bone marrow samples using flow cytometrey.
Time frame: Up to 6 years post first dose
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