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

NCT06846463 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MCC-24-21151HM20031622
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Diffuse Large B-cell Lymphoma; DLBCL - Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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).

  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)

  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.

  Baseline, during protocol treatment, though 2 year follow-up

Study Arms (1)

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

Drug: Zanubrutinib

Interventions

Zanubrutinib DRUG

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.

Investigational Agent Administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Dendritic Cell Sarcoma, Interdigitating

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytic Disorders, Malignant; Histiocytosis

Study Officials

• Bruce Hough, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massey IIT Research Operations

CONTACT

804-628-6430; masseyepd@vcu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: February 26, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2032
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)