PRIMARY OBJECTIVE:~I. To compare the progression-free survival (PFS) of mosunetuzumab versus rituximab in NLPHL patients.~SECONDARY OBJECTIVE:~I. To compare the safety and antitumor activity of NLPHL patients treated with mosunetuzumab versus rituximab.~EXPLORATORY OBJECTIVES:~I. To evaluate CD20 expression and correlate with response. II. To evaluate the molecular effects of mosunetuzumab and rituximab on tumor cells and the immune response and identify biomarkers of response or resistance with ribonucleic acid sequencing (RNAseq), whole exome sequencing (WES), immunohistochemistry (IHC) CD20, PD-1, PD-L1, PD-L2.~III. To evaluate tumor microenvironment and peripheral immune status with single-cell ribonucleic acid sequencing (scRNA-seq).~IV. To evaluate the dynamic molecular response of NLPHL patients treated with rituximab or mosunetuzumab with circulating tumor deoxyribonucleic acid (ctDNA).~V. To evaluate the safety and efficacy (including tumor response, immune response, and overall survival) of the crossover patients.~VI. To assess the association of baseline fludeoxyglucose F-18 (FDG)-positron emission tomography/computed tomography (PET/CT) measurements including metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax), in combination with other risk factors, with PFS and overall survival (OS) in patients with lymphocyte-predominant Hodgkin lymphoma treated with mosunetuzumab or rituximab.~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM I: Patients receive mosunetuzumab subcutaneously (SC) on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience progressive disease (PD) will be permitted to crossover to arm II at week 12. Patients also receive FDG and undergo PET/CT at baseline and end of treatment. Patients who are positive at pre-treatment bone marrow biopsy also receive FDG and undergo PET/CT at week 12. Patients also undergo magnetic resonance imaging (MRI) at baseline, bone marrow biopsy and tissue biopsy at baseline and end of treatment, and blood sample collection at baseline, weeks 4 and 7, end of treatment, and then every 6 months for 2 years.~ARM II: Patients receive rituximab intravenously (IV) on day 1 and rituximab and hyaluronidase human SC on days 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 2 cycles 8 weeks apart in the absence of disease progression or unacceptable toxicity. Patients may receive rituximab IV on days 8, 15, and 22 of each cycle if rituximab and hyaluronidase human is not available. Patients who experience PD will be permitted to crossover to arm I at week 12. Patients also receive FDG and undergo PET/CT at baseline and end of treatment. Patients who are positive at pre-treatment bone marrow biopsy also receive FDG and undergo PET/CT at week 12. Patients also undergo MRI at baseline, bone marrow biopsy and tissue biopsy at baseline and end of treatment, and blood sample collection at baseline, weeks 4 and 7, end of treatment, and then every 6 months for 2 years.~After completion of study treatment, patients are followed up every 3 months for the first year, every 4 months for the second year, and every 6 months for 3 years.
This phase II trial compares mosunetuzumab to the usual treatment (rituximab) for improving survival in patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Rituximab and mosunetuzumab are monoclonal antibodies. They bind to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Mosunetuzumab may be more effective at extending survival in patients with NLPHL than the usual approach with rituximab.