Diffuse Large B-cell LymphomaPhase 2NCT06846463
Zanubrutinib in Patients With DLBCL and MYD88 or NOTCH1 Mutation or CD5+
A Phase 2 study testing Zanubrutinib in people with Diffuse Large B-cell Lymphoma and DLBCL - Diffuse Large B Cell Lymphoma, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
This study is a single-arm, open label, non-randomized, phase 2 trial of zanubrutinib in patients with diffuse large B-cell lymphoma (DLBCL) who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by immunohistochemistry (IHC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma, DLBCL - Diffuse Large B Cell Lymphoma
- What is being tested?
- Zanubrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 27 May 2025to 31 Jul 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a documented pathologic diagnosis of DLBCL at any stage.
- Must have documented MYD88 L265P, CD79B, or NOTCH1 truncation mutation or be CD5+ by IHC.
- Age ≥18 years on the day of signing the informed consent form.
- Patients must have measurable disease on Positron Emission Tomography-Computed Tomography scan (CT/PET) imaging.
- Patient must have received no more than one cycle of R-CHOP prior to enrollment. Length of time between first R-CHOP treatment and planned 2nd R-CHOP treatment should vary by no more than 21 days ± 3 days.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
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- Adequate bone marrow function as defined by:
- Absolute neutrophil count (ANC) ≥1000/mm3, except for patients with bone marrow involvement in which ANC must be ≥500/mm3.
- Platelet ≥75,000/mm3, except for patients with bone marrow involvement in which the platelet count must be ≥30,000/mm3.
- Hemoglobin ≥7 g/dL, after transfusion if necessary
- Adequate organ function defined as:
- Creatinine clearance ≥30 mL/min as estimated by the Cockcroft-Gault equation.
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤2.5 × upper limit of normal (ULN).
- Serum total bilirubin ≤3 x ULN (except patients with Gilberts syndrome 3g/dl).
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
- Women of childbearing potential and men must agree to use one of the following highly effective forms of birth control during the treatment and for 1 month following completion of study treatment for women and for 1 week following completion of study treatment for men.
- combined (estrogen and progestogen containing) hormonal contraception:
- oral
- intravaginal
- transdermal
- progestogen-only hormonal contraception associated with inhibition of ovulation
- oral
- injectable
- implantable
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomized partner
- heterosexual abstinence
- Patients must not have any known allergies, hypersensitivity or intolerance to corticosteroids or monoclonal antibodies.
- Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments.
Who cannot join
- Patients with high grade B-cell lymphoma with myelocytomatosis oncogene /immunoglobulin heavy-chain (MYC)/IGH and BCL-2 rearrangements.
- Patients with brain metastasis.
- Patients with peripheral neuropathy CTCAE grade ≥2.
- Any uncontrolled or clinically significant cardiovascular disease including the following:
- Myocardial infarction within 6 months before screening.
- Unstable angina within 3 months before screening.
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- New York Heart Association class III or IV congestive heart failure.
- History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes).
- Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
- History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
- History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
- Severe or debilitating pulmonary disease in the opinion of the treating investigator.
- Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
- Active fungal, bacterial and/or viral infection requiring systemic therapy.
- Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
- Active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
- Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to undergo monitoring every 4 weeks for HBV reactivation.
- Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.
- Major surgery within 4 weeks of the first dose of study drug.
- Pregnant or lactating women.
- Left ventricular ejection fraction (LVEF) <55% on screening echocardiogram.
- Vaccination or requirement for vaccination with a live vaccine within 28 days prior to the first dose of study drug or at any time during planned study treatment.
- Hypersensitivity to zanubrutinib, rituximab, cyclophosphamide, doxorubicin, vincristine, or prednisone.
- Requires ongoing treatment with a strong CYP3A inducer (Table 3).
- Concurrent participation in another therapeutic clinical trial.
- Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).
- Requires ongoing treatment with warfarin or warfarin derivatives.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Virginia Commonwealth University
Richmond, Virginia, 23298
Massey Heme Malig Team, 804-628-6430, MasseyHemMlg@vcu.edu
Bruce Hough, MD
About this study
Official title: Phase 2 Trial Utilizing Zanubrutinib in Patients With Diffuse Large B-cell Lymphoma and MYD88 L265P Mutations, CD79B Mutations, NOTCH1 Truncation or Who Are CD5+ by IHC.
This study is a single-arm, open label, non-randomized, phase 2 trial of zanubrutinib in patients with diffuse large B-cell lymphoma (DLBCL) who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by immunohistochemistry (IHC).
Read the detailed description
The purpose of this study is to compare effects of adding zanubrutinib to the usual chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by IHC. In those patients with mutations or IHC result, we propose treating with zanubrutinib plus rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (R-CHOP). Patients will be monitored with standard imaging; minimal residual disease (MRD) testing will be optional. The primary outcome is the complete response rate. The secondary outcome is EFS at 2 years. When available, MRD studies will be correlated to response. Patients with aggressive B-cell lymphoma with MYC and BCL-2 and/or BCL-6 mutations will be excluded, as will patients with HIV. Zanubrutinib will be first administered on Cycle 2 Day 1 of R-CHOP. It is up to the discretion of the treating physician how many cycles of R-CHOP the treatment would require, but it is not to exceed 6 cycles of R-CHOP and 5 cycles of zanubrutinib. The number of cycles of R-CHOP should be per standard of care, with the number of zanubrutinib cycles being 1 less than the number of total R-CHOP cycles. Patients will be followed up every 3 months for 24 months after removal from protocol therapy or until death, whichever occurs first. There will be an extended follow-up period of up to 5 years from end of study treatment.
- Being tested
- Zanubrutinib
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Dendritic Cell Sarcoma, Interdigitating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanubrutinibDrug
Investigational Agent Administration. Zanubrutinib will be first administered on Cycle 2 Day 1 of rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (R-CHOP). It is up to the discretion of the treating physician how many cycles of R-CHOP the treatment would require, but it is not to exceed 6 cycles of R-CHOP and 5 cycles of zanubrutinib. The number of cycles of R-CHOP should be per standard of care, with the number of zanubrutinib cycles being 1 less than the number of total R-CHOP cycles.
| Study group | Role | What they receive |
|---|---|---|
| Investigational Agent Administration | Experimental | Zanubrutinib is administered as capsules for oral intake at one of the following dosages based on the discretion of the treating physician:
* 160 mg (two 80-mg capsules) twice daily
* 320 mg (four 80-mg capsules) once daily Receives: Drug: Zanubrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess efficacy of adding oral zanubrutinib to R-CHOP in patients with DLBCL who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by Immunohistochemistry (IHC) in achieving complete response defined by Lugano criteria
Percentage of participants with complete response by immunohistochemistry (IHC).
Measured: Completion of treatment through 2 years +/- 2 weeks
Secondary outcomes (2)
Assess efficacy of adding oral zanubrutinib in addition to R-CHOP in patients with DLBCL who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by IHC in achieving radiographic 2-year EFS and duration of response (DOR)
Percentage of participants with Radiographic 2-year event free survival (EFS) as defined by the time after the first treatment until the date of first treatment failure or death.
Measured: Up to 5 years following end of treatment
Assess the safety of adding oral zanubrutinib in addition to R-CHOP in patients with DLBCL who have a MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by IHC by observing adverse events (AE's) of special interest.
Occurrence of hematologic and non-hematologic toxicity as defined by the percent of patients who have each toxicity over all 6 cycles. Adverse events of special interest hematologic toxicity including:
- Neutropenic fever
- All grades of anemia
- Neutropenia and thrombocytopenia as defined by the percent of patients who have this AE over all 6 cycles.
Non-hematologic toxicity including:
- Fungal infection
- Bacterial pneumonia
- Rash as defined by the percent of patients who have this AE over all 6 cycles
Measured: Baseline, during protocol treatment, though 2 year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2025
- Study start27 May 2025
- Primary completion31 Jul 2029 (estimated)
- Study completion31 Jul 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe 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
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruce Hough, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06846463
- Sponsor's protocol ID
- MCC-24-21151
- Other IDs
- HM20031622
- Status last verified
- Jan 2026
- First submitted
- 20 Feb 2025
- Last updated
- 23 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There are no plans to share IPD at this time.
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial Utilizing Zanubrutinib in Patients With Diffuse Large B-cell Lymphoma and MYD88 L265P Mutations, CD79B Mutations, NOTCH1 Truncation or Who Are CD5+ by IHC.
- ClinicalTrials.gov ID
- NCT06846463
- Acronym / sponsor ID
- MCC-24-21151
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- 27 May 2025 (actual)
- Primary completion
- 31 Jul 2029 (estimated)
- Study completion
- 31 Jul 2032 (estimated)
- First posted
- 26 Feb 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 single-arm, open label, non-randomized, phase 2 trial of zanubrutinib in patients with diffuse large B-cell lymphoma (DLBCL) who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by immunohistochemistry (IHC).
Detailed description
The purpose of this study is to compare effects of adding zanubrutinib to the usual chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by IHC. In those patients with mutations or IHC result, we propose treating with zanubrutinib plus rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (R-CHOP). Patients will be monitored with standard imaging; minimal residual disease (MRD) testing will be optional. The primary outcome is the complete response rate. The secondary outcome is EFS at 2 years. When available, MRD studies will be correlated to response. Patients with aggressive B-cell lymphoma with MYC and BCL-2 and/or BCL-6 mutations will be excluded, as will patients with HIV. Zanubrutinib will be first administered on Cycle 2 Day 1 of R-CHOP. It is up to the discretion of the treating physician how many cycles of R-CHOP the treatment would require, but it is not to exceed 6 cycles of R-CHOP and 5 cycles of zanubrutinib. The number of cycles of R-CHOP should be per standard of care, with the number of zanubrutinib cycles being 1 less than the number of total R-CHOP cycles. Patients will be followed up every 3 months for 24 months after removal from protocol therapy or until death, whichever occurs first. There will be an extended follow-up period of up to 5 years from end of study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Investigational Agent Administration | Experimental | Drug: ZanubrutinibZanubrutinib is administered as capsules for oral intake at one of the following dosages based on the discretion of the treating physician: * 160 mg (two 80-mg capsules) twice daily * 320 mg (four 80-mg capsules) once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Patients must have a documented pathologic diagnosis of DLBCL at any stage.
- Must have documented MYD88 L265P, CD79B, or NOTCH1 truncation mutation or be CD5+ by IHC.
- Age ≥18 years on the day of signing the informed consent form.
- Patients must have measurable disease on Positron Emission Tomography-Computed Tomography scan (CT/PET) imaging.
- Patient must have received no more than one cycle of R-CHOP prior to enrollment. Length of time between first R-CHOP treatment and planned 2nd R-CHOP treatment should vary by no more than 21 days ± 3 days.
Key exclusion criteria (27 listed)
- Patients with high grade B-cell lymphoma with myelocytomatosis oncogene /immunoglobulin heavy-chain (MYC)/IGH and BCL-2 rearrangements.
- Patients with brain metastasis.
- Patients with peripheral neuropathy CTCAE grade ≥2.
- Any uncontrolled or clinically significant cardiovascular disease including the following:
- Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
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 |
|---|---|---|
| ZanubrutinibInvestigational Agent Administration. Zanubrutinib will be first administered on Cycle 2 Day 1 of rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (R-CHOP). It is up to the discretion of the treating physician how many cycles of R-CHOP the treatment would require, but it is not to exceed 6 cycles of R-CHOP and 5 cycles of zanubrutinib. The number of cycles of R-CHOP should be per standard of care, with the number of zanubrutinib cycles being 1 less than the number of total R-CHOP cycles. | Drug | Investigational Agent Administration |
Primary outcome
Assess efficacy of adding oral zanubrutinib to R-CHOP in patients with DLBCL who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by Immunohistochemistry (IHC) in achieving complete response defined by Lugano criteria
Time frame: Completion of treatment through 2 years +/- 2 weeks
Percentage of participants with complete response by immunohistochemistry (IHC).
2 secondary outcomes
Assess efficacy of adding oral zanubrutinib in addition to R-CHOP in patients with DLBCL who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by IHC in achieving radiographic 2-year EFS and duration of response (DOR)
Time frame: Up to 5 years following end of treatment
Assess the safety of adding oral zanubrutinib in addition to R-CHOP in patients with DLBCL who have a MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by IHC by observing adverse events (AE's) of special interest.
Time frame: Baseline, during protocol treatment, though 2 year follow-up
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 23 Jan 2026.
- Individual participant dataSharing planned: No. There are no plans to share IPD at this time.
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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.
Bruce Hough, MD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zanubrutinib in people with Diffuse Large B-cell Lymphoma and DLBCL - Diffuse Large B Cell Lymphoma, run by Virginia Commonwealth University at 1 site in United States.
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 31 inclusion and 27 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: looking for participants now, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 Massey IIT Research Operations (804-628-6430, masseyepd@vcu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess efficacy of adding oral zanubrutinib to R-CHOP in patients with DLBCL who have an MYD88 L265P mutation, a CD79B mutation, a NOTCH1 truncation, or who are CD5+ by Immunohistochemistry (IHC) in achieving complete response defined by Lugano criteria (time frame: Completion of treatment through 2 years +/- 2 weeks). 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 23 Jan 2026.