Zanubrutinib in Patients With DLBCL and MYD88 or NOTCH1 Mutation or CD5+

Q: What is the NCT06846463 clinical trial studying?

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). The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Q: Who can participate in NCT06846463?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

Q: How do I contact the trial site for NCT06846463?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Q: Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Q: Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

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.

Zanubrutinib in Patients With DLBCL and MYD88 or NOTCH1 Mutation or CD5+ (NCT06846463) is a Phase 2 interventional studying Diffuse Large B-cell Lymphoma and DLBCL - Diffuse Large B Cell Lymphoma, sponsored by Virginia Commonwealth University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Diffuse Large B-cell Lymphoma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 21 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 willing to sign a consent form 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. - 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 count at least 75,000/mm3, except for patients with bone marrow involvement in which the platelet count must be ≥30,000/mm3. - blood count (hemoglobin) at least 7 g/dL, after transfusion if necessary - your organs (liver, kidneys, etc.) are working well enough based on blood tests defined as: - kidney function (creatinine clearance) at least 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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. * 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. Exclusion Criteria: * 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. * 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.

Treatments Being Tested

DRUG

Zanubrutinib

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.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Virginia Commonwealth University

Richmond, Virginia, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06846463), the sponsor (Virginia Commonwealth University), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06846463 clinical trial studying?

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). The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06846463?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06846463?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06846463. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06846463. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.