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.
PRIMARY OBJECTIVE: I. To compare the progression-free survival (PFS) of mosunetuzumab versus rituximab in NLPHL patients. SECONDARY OBJECTIVES: I. To compare the safety and antitumor activity of NLPHL patients treated with mosunetuzumab versus rituximab. 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). EXPLORATORY OBJECTIVES: I. To evaluate CD20 expression and correlate with response. II. To evaluate the dynamic molecular response of NLPHL patients treated with rituximab or mosunetuzumab with circulating tumor deoxyribonucleic acid (ctDNA). III. To evaluate the safety and efficacy (including tumor response, immune response, and overall survival) of the crossover patients. IV. 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 on study. Patients also undergo bone marrow biopsy and tissue biopsy at baseline, and blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy and tissue biopsy at end of treatment. 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 on study. Patients also undergo bone marrow biopsy and tissue biopsy at baseline, and blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy and tissue biopsy at end of treatment. After completion of study treatment, patients are followed up every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Undergo tissue biopsy
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo PET/CT
Receive FDG
Given SC
Undergo PET/CT
Given IV
Given SC
City of Hope Comprehensive Cancer Center
Duarte, California, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, United States
Progression-free survival (PFS) time
Will be assessed according to the Lugano/Lymphoma Response to Immunomodulatory Therapy Criteria classification. The overall PFS curve will be displayed by treatment arm using the Kaplan-Meier (KM) method, and statistical comparisons will be performed by a log-rank test.
Time frame: Time from the date of randomization to the first objective documentation of disease progression or death due to any cause, assessed up to 2 years
Objective response
The count and incidence rate of the response categories will be summarized for the overall population and by each treatment arm with a 95% exact confidence intervals. Comparison between treatment arms will be performed by a chi-squared test.
Time frame: At week 12 and end of treatment
Duration of response
Will be displayed by treatment arm using the KM method, and statistical comparisons will be performed by a log-rank test.
Time frame: Time from the first date of partial or complete response until death or the assessment date of disease progression, assessed up to 2 years
Overall survival (OS)
Will be displayed by randomized treatment arm using the KM method, and statistical comparisons will be performed by a log-rank test.
Time frame: Time from the date of randomization to death due to any cause, assessed up to 2 years
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UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, United States
RECRUITINGUniversity of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
RECRUITING...and 25 more locations