Waldenström Macroglobulinemia (WM)Phase 2ZBR in WMNCT07259122
A Phase II Clinical Study of Zanubrutinib Combined With Four Cycles of CD20 Monoclonal Antibody and Reduced-Dose Bendamustine in the Treatment of Untreated Waldenström Macroglobulinemia
A Phase 2 study testing Zaunbrutinib, Bendamustine and Rituximab for induction therapy and Zanubrutinib mono therapy for maintenance treatment in people with Waldenström Macroglobulinemia (WM), run by Institute of Hematology & Blood Diseases Hospital, China at 2 sites in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Waldenström Macroglobulinemia (WM)
- What is being tested?
- Zaunbrutinib, Bendamustine and Rituximab for induction therapy and Zanubrutinib mono therapy for maintenance treatment
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 2 sitesChina
- Study dates
- 30 Dec 2025to 30 Jun 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Male or female patients aged ≥18 years.
- 2. Must meet the diagnostic criteria for Waldenström's Macroglobulinemia (WM).
- 3. Patients must be treatment-naïve or not have received standard prior therapy, as defined by the following conditions: a) No prior combined chemotherapy with regimens such as BR, RCD, BCD, CHOP, or COP. b) No prior therapy with fludarabine-containing regimens. c) Treatment with chlorambucil or cyclophosphamide (alone or in combination with glucocorticoids) for less than 4 weeks. d) Failure to achieve a minimal response (MR) from the above treatments. e) If any of the above treatments were previously administered, a washout period of at least 2 weeks must be completed before study treatment initiation.
- 4. Presence of indications for WM treatment, meeting at least one of the following criteria: a) Symptomatic hyperviscosity. b) Symptomatic peripheral neuropathy. c) Amyloidosis. d) Cold agglutinin disease; cryoglobulinemia. e) Disease-related cytopenia (Hemoglobin <100 g/L or Platelet count <100×10^9/L). f) Massive lymphadenopathy. g) Presence of constitutional symptoms: persistent/recurrent fever (>38°C) for over 2 weeks unrelated to infection, drenching night sweats, and/or unintentional weight loss >10% within 6 months. h) Rapid disease progression, defined as a >50% increase in lymph node size within 2 months, and/or lymphocyte doubling time <6 months, and/or rapid decline in hemoglobin or platelet counts not due to autoimmune causes. i) Evidence of histologic transformation.
- 5. ECOG Performance Status score of ≤2.
- 6. Laboratory values meeting the following criteria within the screening period: Absolute Neutrophil Count (ANC) ≥ 0.75 × 10^9/L; Platelet count ≥ 50 × 10^9/L; Total Bilirubin ≤ 2 × Upper Limit of Normal (ULN); Alanine Aminotransferase (ALT) / Aspartate Aminotransferase (AST) ≤ 3 × ULN; Calculated creatinine clearance ≥ 30 mL/min (using Cockcroft-Gault formula)
- 7. Life expectancy of ≥ 6 months.
Who cannot join
- 1. Diagnosis or treatment for any malignancy other than B-cell non-Hodgkin lymphoma (B-NHL) within the past year (including active central nervous system lymphoma).
- 2. Clinical evidence of transformation to large cell lymphoma.
- 3.Pre-existing severe hepatic or renal impairment unrelated to lymphoma: ALT > 3 × ULN; AST > 3 × ULN; Total Bilirubin > 2 × ULN; Estimated creatinine clearance < 30 mL/min
- 4.Any other severe concurrent medical condition that would, in the investigator's judgment, compromise the patient's ability to participate in the study (e.g., uncontrolled diabetes, gastric ulcer, significant cardiac or pulmonary disease, etc.). The final determination rests with the investigator.
- 5. Known history of human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotic therapy. Note: Active HBV infection is defined by ALL of the following criteria: a. HBV DNA ≥ 2000 IU/mL; b. ALT ≥ 2 × ULN; c. Hepatitis not attributable to other causes such as the underlying disease or drugs. Patients with initially active HBV who convert to an inactive carrier state after antiviral therapy may be enrolled if they receive adequate concomitant antiviral prophylaxis.
- 6. Symptomatic central nervous system dysfunction or involvement (Bing-Neel syndrome).
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- 7. Major surgery within 14 days prior to the first dose of study drug or anticipated requirement for major surgery during the study treatment period (excluding lymph node biopsy).
- 8. Inability to swallow capsules, or conditions significantly affecting gastrointestinal function (e.g., malabsorption syndrome, status post-gastrectomy or small bowel resection, symptomatic inflammatory bowel disease, ulcerative colitis, partial or complete intestinal obstruction).
- 9. Requirement for concurrent strong Cytochrome P450 (CYP) 3A inhibitors.
- 10. Pregnancy or lactation. Women of childbearing potential unwilling to use effective contraception during the study period.
- 11. Known hypersensitivity to any of the study drugs or their excipients.
- Withdrawal Criteria
- 1. Disease progression during treatment (after ≥2 cycles of therapy) or failure to achieve at least a minimal response (MR) after 6 cycles of therapy.
- 2. Occurrence of intolerable adverse events or complications.
- 3. Patient's voluntary decision to withdraw consent for continued treatment.
- 4. Pregnancy during the study.
- 5. Investigator's judgment that the patient should discontinue treatment for any other reason.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites
China Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
Tianjin, China, 300020
Institute of Hematology & Blood Diseases Hospital, China
Tianjin, Tianjin Municipality, 300020
About this study
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
- Conditions
- Waldenström Macroglobulinemia (WM)
- Being tested
- Zaunbrutinib, Bendamustine and Rituximab for induction therapy, Zanubrutinib mono therapy for maintenance treatment
- Keywords
- zanubrutinib, bendamustine
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zaunbrutinib, Bendamustine and Rituximab for induction therapyDrug
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.
Zanubrutinib mono therapy for maintenance treatmentDrug
Patients will then continue with zanubrutinib monotherapy maintenance for 8 months before treatment discontinuation.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: ZBR | Experimental | Not described Receives: Drug: Zaunbrutinib, Bendamustine and Rituximab for induction therapy; Drug: Zanubrutinib mono therapy for maintenance treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best deep response rate(≥VGPR)
defined as the rate of very good partial response VGPR or CR
Measured: up to 1 year
Secondary outcomes (11)
MRD Negativity Rate at End of Treatment
MRD Negativity Rate at End of Treatment
Measured: 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.
Measured: 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
Measured: up to 1 year
Complete Response (CR) Rate
To assess CR rate at the end of treatment
Measured: 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
Measured: up to 1 year
Time to First Response
Time to First Observed Response During Treatment
Measured: up to 1 year
Time to Best Response
Time to the Best Response
Measured: 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
Measured: 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.
Measured: 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
Measured: up to 3 years
Treatment-Related Adverse Events (AEs)
Incidence of adverse events, serious adverse events and significant adverse event
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2025
- Study start30 Dec 2025 (estimated)
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Waldenström Macroglobulinemia (WM)Studies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shuhua Yi, Principal investigator, Institute of Hematology & Blood Diseases Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07259122
- Sponsor's protocol ID
- IIT2025111
- Acronym
- ZBR in WM
- Status last verified
- Nov 2025
- First submitted
- 14 Nov 2025
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Study of Zanubrutinib Combined With Four Cycles of CD20 Monoclonal Antibody and Reduced-Dose Bendamustine in the Treatment of Untreated Waldenström Macroglobulinemia
- ClinicalTrials.gov ID
- NCT07259122
- Acronym / sponsor ID
- ZBR in WM / IIT2025111
- Conditions
- Waldenström Macroglobulinemia (WM)
- Keywords
- zanubrutinib, bendamustine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 43 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 30 Dec 2025 (estimated)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2032 (estimated)
- First posted
- 2 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: ZBR | Experimental | Drug: Zaunbrutinib, Bendamustine and Rituximab for induction therapy, Drug: Zanubrutinib mono therapy for maintenance treatment |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1. Male or female patients aged ≥18 years.
- 2. Must meet the diagnostic criteria for Waldenström's Macroglobulinemia (WM).
- 3. Patients must be treatment-naïve or not have received standard prior therapy, as defined by the following conditions: a) No prior combined chemotherapy with regimens such as BR, RCD, BCD, CHOP, or COP. b) No prior therapy with fludarabine-containing regimens. c) Treatment with chlorambucil or cyclophosphamide (alone or in combination with glucocorticoids) for less than 4 weeks. d) Failure to achieve a minimal response (MR) from the above treatments. e) If any of the above treatments were previously administered, a washout period of at least 2 weeks must be completed before study treatment initiation.
- 4. Presence of indications for WM treatment, meeting at least one of the following criteria: a) Symptomatic hyperviscosity. b) Symptomatic peripheral neuropathy. c) Amyloidosis. d) Cold agglutinin disease; cryoglobulinemia. e) Disease-related cytopenia (Hemoglobin <100 g/L or Platelet count <100×10^9/L). f) Massive lymphadenopathy. g) Presence of constitutional symptoms: persistent/recurrent fever (>38°C) for over 2 weeks unrelated to infection, drenching night sweats, and/or unintentional weight loss >10% within 6 months. h) Rapid disease progression, defined as a >50% increase in lymph node size within 2 months, and/or lymphocyte doubling time <6 months, and/or rapid decline in hemoglobin or platelet counts not due to autoimmune causes. i) Evidence of histologic transformation.
- 5. ECOG Performance Status score of ≤2.
Key exclusion criteria (17 listed)
- 1. Diagnosis or treatment for any malignancy other than B-cell non-Hodgkin lymphoma (B-NHL) within the past year (including active central nervous system lymphoma).
- 2. Clinical evidence of transformation to large cell lymphoma.
- 3.Pre-existing severe hepatic or renal impairment unrelated to lymphoma: ALT > 3 × ULN; AST > 3 × ULN; Total Bilirubin > 2 × ULN; Estimated creatinine clearance < 30 mL/min
- 4.Any other severe concurrent medical condition that would, in the investigator's judgment, compromise the patient's ability to participate in the study (e.g., uncontrolled diabetes, gastric ulcer, significant cardiac or pulmonary disease, etc.). The final determination rests with the investigator.
- 5. Known history of human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotic therapy. Note: Active HBV infection is defined by ALL of the following criteria: a. HBV DNA ≥ 2000 IU/mL; b. ALT ≥ 2 × ULN; c. Hepatitis not attributable to other causes such as the underlying disease or drugs. Patients with initially active HBV who convert to an inactive carrier state after antiviral therapy may be enrolled if they receive adequate concomitant antiviral prophylaxis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zaunbrutinib, Bendamustine and Rituximab for induction therapyPatients 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. | Drug | Experimental: ZBR |
| Zanubrutinib mono therapy for maintenance treatmentPatients will then continue with zanubrutinib monotherapy maintenance for 8 months before treatment discontinuation. | Drug | Experimental: ZBR |
Primary outcome
Best deep response rate(≥VGPR)
Time frame: up to 1 year
defined as the rate of very good partial response VGPR or CR
11 secondary outcomes
MRD Negativity Rate at End of Treatment
Time frame: up to the end of treatment
Duration of Response
Time frame: up to 3 years
Objective Response Rate (ORR)
Time frame: up to 1 year
Complete Response (CR) Rate
Time frame: up to 1 year
Major Response Rate (MRR, ≥ Partial Response)
Time frame: up to 1 year
Time to First Response
Time frame: up to 1 year
Time to Best Response
Time frame: up to the end of treatment
Progression-Free Survival (PFS)
Time frame: up to 3 years
Overall Survival (OS) Rate
Time frame: up to 3 years
Time to Next Treatment (TTNT)
Time frame: up to 3 years
Treatment-Related Adverse Events (AEs)
Time frame: up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Shuhua Yi principal investigator
Institute of Hematology & Blood Diseases Hospital, China
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zaunbrutinib, Bendamustine and Rituximab for induction therapy and Zanubrutinib mono therapy for maintenance treatment in people with Waldenström Macroglobulinemia (WM), run by Institute of Hematology & Blood Diseases Hospital, China at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shuhua Yi, Dr (+86-022-23608109, yishuhua@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best deep response rate(≥VGPR) (time frame: up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.