ClinicalTrials.gov record NCT07259122
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 II Clinical Study of Zanubrutinib Combined With Four Cycles of CD20 Monoclonal Antibody and Reduced-Dose Bendamustine in the Treatment of Untreated Waldenström Macroglobulinemia
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase II study enrolls treatment‑naïve symptomatic Waldenström macroglobulinemia patients. Participants receive four 4‑week cycles of zanubrutinib combined with reduced‑dose bendamustine and a CD20 monoclonal antibody (rituximab), followed by eight months of zanubrutinib alone. Response and minimal residual disease (MRD) are assessed during treatment and up to 12 months after completion. Patients are withdrawn for disease progression, lack of response, intolerable side effects, pregnancy, or investigator decision.
What it is studying. The study tests the ZBR regimen (zanubrutinib + reduced‑dose bendamustine + CD20 antibody) to see if it produces deep responses (very good partial response or complete response) and MRD‑negative status in untreated symptomatic WM.
What the researchers hope to learn. To measure the best deep response rate (≥VGPR), MRD negativity at end of treatment, objective and complete response rates, duration of response, progression‑free and overall survival, time to next treatment, and treatment‑related adverse events.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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 Patients will be withdrawn from the study if they experience disease progression (PD) or show no response to treatment.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
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Zaunbrutinib, Bendamustine and Rituximab for induction therapy
- Zanubrutinib mono therapy for maintenance treatment
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Male or female patients aged ≥18 years.
- Must meet the diagnostic criteria for Waldenström's Macroglobulinemia (WM).
- 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.
- 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.
- ECOG Performance Status score of ≤2.
- 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)
- Life expectancy of ≥ 6 months.
Exclusion criteria
- 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).
- Clinical evidence of transformation to large cell lymphoma.
- 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
- 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.
- 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.
- Symptomatic central nervous system dysfunction or involvement (Bing-Neel syndrome).
- 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).
- 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).
- Requirement for concurrent strong Cytochrome P450 (CYP) 3A inhibitors.
- Pregnancy or lactation. Women of childbearing potential unwilling to use effective contraception during the study period.
- Known hypersensitivity to any of the study drugs or their excipients.
- Withdrawal Criteria
- Disease progression during treatment (after ≥2 cycles of therapy) or failure to achieve at least a minimal response (MR) after 6 cycles of therapy.
- Occurrence of intolerable adverse events or complications.
- Patient's voluntary decision to withdraw consent for continued treatment.
- Pregnancy during the study.
- Investigator's judgment that the patient should discontinue treatment for any other reason.
Study description and what participation involves
The registry record has no detailed description beyond the summary above.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants receive four 28‑day cycles of combination therapy: continuous oral zanubrutinib (160 mg twice daily), intravenous bendamustine on Days 1–2 of cycles 1–4, and an IV CD20 monoclonal antibody on Day 0 of cycles 1–4, followed by about 8 months of zanubrutinib alone. They will attend regular clinic visits for exams, safety monitoring and efficacy assessments (including evaluations every three cycles). Bone marrow and blood tests for minimal residual disease (MRD) will be performed at the end of cycles 3 and 6 and again 12 months after treatment completion (bone marrow sampling is an invasive procedure). Participants may be withdrawn for disease progression, lack of response, intolerable side effects, pregnancy, or investigator decision.
How the study is structured. Open‑label, single‑group Phase II treatment trial: all participants receive the same assigned regimen (four cycles of combination therapy, then zanubrutinib maintenance). There is no randomization or placebo. Response assessments, including MRD checks, are done during treatment and in follow‑up.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- The listed sites are in China. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Dec 30, 2025 (estimated)
- Primary completion
- Jun 30, 2028 (estimated)
- Study completion
- Jun 30, 2032 (estimated)
- Target enrollment
- 43 participants (estimated)
- Last updated on registry
- Dec 2, 2025
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, China
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Shuhua Yi, Dr 📞 +86-022-23608109 ✉ yishuhua@ihcams.ac.cn
- Wenjie Xiong 📞 +86-022-23608123 ✉ xiongwenjie@ihcams.ac.cn
Participating sites (2)
- China Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
Tianjin, China, 300020 · China
- Institute of Hematology & Blood Diseases Hospital, China
Tianjin, Tianjin Municipality, 300020 · China
Terms used on this page · explanations by MedicalUpdates.ai
- treatment-naïve
- Has not previously received the treatment, or the type of treatment, that the study is about.
- Minimal residual disease
- Very small amounts of disease that remain after treatment and can only be found with highly sensitive tests. 'MRD-negative' means none was detected at the test's limit. The exact test and threshold depend on the condition and the study.
- prior therapy
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- glucocorticoids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- washout period
- A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
- ECOG Performance Status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- screening period
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- Absolute Neutrophil Count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- Upper Limit of Normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- Life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- Women of childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- adverse events
- Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials