NCT06561347 · Massachusetts General Hospital
Zanubrutinib, Bendamustine, Rituximab Prev. Untreated WM
(ZEBRA)
What this study is about
The purpose of this study is to determine the very good significant shrinkage of disease signs (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM). The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.
View original scientific description
The purpose of this study is to determine the very good partial response (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM). The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.
Interventions
DRUG
Zanubrutinib
A potent, specific, and irreversible Bruton tyrosine kinase (BTK) inhibitor
DRUG
Bendamustine
Alkylating agent
DRUG
Rituximab
Monoclonal antibody
Primary outcome measures
Very Good Partial Response (VGPR) or Better Response Rate
Time frame: Day 1 to 5 years post treatment
Assessed using 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM11) criteria. All participants will be gauged for very good partial response (VGPR) rate or better.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Clinicopathological diagnosis of waldenström macroglobulinemia (WM) per the second international workshop on waldenström macroglobulinemia (IWWM2) criteria
- Presence of any MYD88 and CXCR4 mutation status, including MYD88 L265P mutation plus CXCR4 wild type, MYD88 L265P mutation plus CXCR4 mutation, or MYD88 wild type
- Meeting criteria for treatment per IWWM2 criteria. At least one of the following:
- Constitutional Symptoms (at least one of the following)
- Recurrent fever
- Night sweats
- Weight loss
- Progressive or symptomatic lymphadenopathy or splenomegaly
- Hemoglobin ≤ 10 g/dL
- Platelet count ≤ 100 k/uL
- Hyperviscosity syndrome
- Symptomatic peripheral neuropathy
- Systemic amyloidosis
- Renal insufficiency
- Symptomatic cryoglobulinemia or cold agglutinemia
- Treatment naive; must have not received any prior systemic therapy for WM
- Participants with suspected or symptomatic hyperviscosity (e.g. noseblee
Where
- Denver, Colorado
- Boston, Massachusetts
- Dallas, Texas
Collaborators
BeOne Medicines
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 8, 2026 · Source of record for eligibility and locations