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.
PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of the mosunetuzumab (M) plus dose-adjusted (DA) etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone \[EPOCH\] combination in previously untreated c-Myc + high-grade B cell lymphoma. (Phase Ib) II. Evaluate the efficacy of M DA EPOCH as complete response (CR) in previously untreated c-Myc + high grade B cell lymphoma. (Phase II) SECONDARY OBJECTIVES: I. Evaluate the efficacy of M DA EPOCH in Phase Ib and II as overall response, durability of response, and survival. II. Ongoing evaluation of the toxicity and tolerability of M DA EPOCH. (Phase Ib and II) III. Summarize DA EPOCH treatment details when received as part of M DA EPOCH. (Phase Ib and II) EXPLORATORY OBJECTIVES: I. Assess utilization and benefit of tocilizumab for toxicity management. (Phase Ib and II) II. Assess toxicity of M DA EPOCH based on immune related AEs (irAEs). (Phase Ib and II) III. Identify baseline factors of response and progression. (Phase Ib and II) IV. Assess the immune response to mosunetuzumab in the setting of the M DA EPOCH regimen. (Phase Ib and II) OUTLINE: Patients receive mosunetuzumab intravenously (IV), over 2-4 hours, on day 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Patients receive etoposide IV, doxorubicin IV, and vincristine IV on days 1-4, cyclophosphamide IV, over 2 hours, on day 5 and prednisone orally (PO) twice per day (BID) on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity for up to 6 cycles. Patients undergo bone marrow aspiration and biopsy, tumor biopsy and may undergo echocardiography or multigated acquisition scan (MUGA) at screening and positron emission tomography (PET) scan, computed tomography (CT) scan or magnetic resonance imaging (MRI) and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Undergo tumor biopsy
Undergo blood sample collection
Undergo bone marrow aspiration and biopsy
Undergo CT scan
Given IV
Given IV
Undergo echocardiography
Given IV
Undergo MRI
Given IV
Undergo MUGA
Undergo PET scan
Given PO
Given IV
OHSU Knight Cancer Institute
Portland, Oregon, United States
RECRUITINGIncidence 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 graded with the American Society for Transplantation and Cellular Therapy (ASTCT) system. Safe dose of mosunetuzumab (or dose adjusted \[DA\] etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone \[EOPCH\]) will be specified.
Time frame: From the first dose of mosunetuzumab to the end of cycle 2 (1 cycle = 21 days)
Proportion of patients with complete response by positron emission tomography-computed tomography (PET-CT) (phase II)
Will be reported with exact 95% confidence interval.
Time frame: Up to 5 years
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.
Time frame: Up to 5 years
Duration of response (DOR)
Descriptive statistics such as median DOR, with minimum and maximum DOR, will be reported by mosunetuzumab dose level if applicable.
Time frame: From first documented evidence of documented CR or PR to first occurrence of disease progression as determined by the investigator, or death from any cause, whichever occurs first, assessed up to 5 years
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.
Time frame: From the first dose of mosunetuzumab to first occurrence of disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first, assessed up to 5 years
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.
Time frame: From first dose of mosunetuzumab to death by any cause, assessed up to 5 years
Incidence of ≥ grade 3 toxicities possibly or definitely related to mosunetuzumab
Per ASTCT for CRS and ICANS;CTCAE v5.0 otherwise
Time frame: Up to to 30 days after last dose of mosunetuzumab
Number of cycles completed and dose received of DA EPOCH
Time frame: Up to to 30 days after last dose of DA EPOCH
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