Comparing the Effectiveness of the Immunotherapy Agents Rituximab or Mosunetuzumab in Patients With Nodular Lymphocyte-Predominant Hodgkin Lymphoma, NORM Trial
Start Date
1/23/2024
Completion Date
10/31/2026
Summary
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.
Detailed Description
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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biopsy Procedure
Biospecimen Collection
Bone Marrow Biopsy
Computed Tomography
Fludeoxyglucose F-18
Mosunetuzumab
Positron Emission Tomography
Rituximab
Rituximab and Hyaluronidase Human
Conditions
Locations
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida 33180
United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146
United States
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida 33065
United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442
United States
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida 33166
United States
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida 33021
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida 33176
United States
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida 33181
United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida 33324
United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri 64116
United States
University of Kansas Cancer Center - North
Kansas City, Missouri 64154
United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri 64116
United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey 07920
United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey 07748
United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey 07645
United States
Memorial Sloan Kettering Commack
Commack, New York 11725
United States
Memorial Sloan Kettering Westchester
Harrison, New York 10604
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Memorial Sloan Kettering Nassau
Uniondale, New York 11553
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio 45219
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio 45069
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
UT MD Anderson Cancer Center
Houston, Texas 77030
United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario M5G 2M9
Canada