This phase Ib/II clinical trial tests the safety, side effects, and effectiveness of mosunetuzumab with chemotherapy for the treatment of patients with untreated, c-Myc rearrangement positive, high grade B cell lymphoma or diffuse large B cell lymphoma. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as mosunetuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone work in different ways to stop the growth of cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving mosunetuzumab with chemotherapy may be safe, tolerable and/or effective in treating patients with untreated, c-Myc rearrangement positive, high grade B cell lymphoma or diffuse large B cell lymphoma.
For both phases of the study, participant must be 18-75 years of age and have previously untreated high-grade B cell lymphoma (HGBCL) or diffuse large B cell lymphoma (DLBCL), including transformed DLBCL per the World Health Organization (WHO) 2022 classification, and with documented c-Myc rearrangement on fluorescence in situ hybridization (FISH) testing. Eligible types of c-Myc rearrangements will be performed by FISH testing and may include any single MYC rearrangement (single-hit lymphoma [SHL]), Double hit (DHL) lymphoma or and triple hit (THL) lymphoma defined by translocations of MYC and BCL2 (DHL) and BCL6 (THL)
Pathology must be verified and confirmed by university pathologists at the enrolling institution and centrally (OHSU) for any biopsies read outside of either institution
Stage II or higher and International Prognostic Index (IPI) score of 2-5
Able to comply with the study protocol and procedures, in the investigator's judgment
Pregnant or breast /chestfeeding
Course of bendamustine plus rituximab (BR) treatment > 3 years prior for follicular lymphoma, or any history of rituximab treatment
Prednisone of ≤ 100 mg for up to a total of 14 days. Prednisone or equivalent corticosteroid must be discontinued by the time of treatment start. These days do NOT have to be consecutive (i.e., can include multiple courses as long as ≤ 14 days)
One cycle of RCHOP (can be dose reduced) or DA R EPOCH or BR or single agent rituximab
Single group
Biopsy
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration and Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Computed Tomography
Procedure/SurgeryUndergo CT scan
Cyclophosphamide
DrugGiven IV
Doxorubicin
DrugGiven IV
Echocardiography
Procedure/SurgeryUndergo echocardiography
Etoposide
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Mosunetuzumab
Biological/VaccineGiven IV
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Positron Emission Tomography
Procedure/SurgeryUndergo PET scan
Prednisone
DrugGiven PO
Vincristine
DrugGiven IV
Incidence of dose limiting toxicities (DLTs) (phase Ib)
Using a modified 3+3 design in previously untreated c-Myc rearranged aggressive B cell lymphomas during the safety run-in period (cycle 1-2). Incidence of DLTs will be tabulated by dose level. All DLTs will be coded by system organ class, MedDRA preferred term, and severity grade using Common Terminology Criteria for Adverse Events (CTCAE )(version \[v\] 5.0). Cytokine Release Syndrome/Immune Effector Cell-Associated Neurotoxicity Syndrome (CRS/ICANS) toxicities will be reporting using with the American Society for Transplantation and Cellular Therapy (ASTCT) grading system. Safe dose of mosunetuzumab (or dose adjusted \[DA\] etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone \[EOPCH\]) will be specified.
Proportion of patients with complete response by positron emission tomography-computed tomography (PET-CT) (phase II)
Will be reported with exact 95% confidence interval.
Overall response rate (ORR) by PET-CT
ORR defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) among all efficacy evaluable participants by the EOT disease assessment. Will be reported with exact 95% confidence interval, by mosunetuzumab dose level if applicable.
Duration of response (DOR)
Descriptive statistics such as median DOR, with minimum and maximum DOR, will be reported by mosunetuzumab dose level if applicable.
Progression free survival (PFS)
Are estimated in the efficacy set using the Kaplan Meier method. We will report median PFS and corresponding 95% confidence interval for participants by mosunetuzumab dose level if applicable.
Overall survival (OS)
Are estimated in the efficacy set using the Kaplan Meier method. We will report median OS and corresponding 95% confidence interval for participants by mosunetuzumab dose level if applicable.
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OHSU Knight Cancer Institute
Lead sponsor
Genentech, Inc.
Collaborator
Oregon Health and Science University
Collaborator
