Zanubrutinib in Patients With DLBCL and MYD88 or NOTCH1 Mutation or CD5+
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVirginia Commonwealth University
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Myocardial infarction within 6 months before screening.
Trial design
Design model
Single group
Treatments tested in this trial
Zanubrutinib
DrugInvestigational 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.
Treatment groups
21 Participants
are divided into 1 treatment groupGroup A: Investigational Agent AdministrationExperimental treatment 1 intervention
Trial outcomes
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).
Time frame
Completion of treatment through 2 years +/- 2 weeksSecondary outcomes
1
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.
Time frame
Up to 5 years following end of treatment2
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
Time frame
Baseline, during protocol treatment, though 2 year follow-upSponsors and contacts
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Source ClinicalTrials.gov