Comparing the Effectiveness of the Immunotherapy Agents Rituximab or Mosunetuzumab in Patients With Nodular Lymphocyte-Predominant Hodgkin Lymphoma, NORM Trial
NORM: Nodular Lymphocyte-Predominant Hodgkin Lymphoma Patients Treated in a Randomized Phase 2 Trial With Either Rituximab or Mosunetuzumab
3 other identifiers
interventional
70
2 countries
36
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2024
Typical duration for phase_2
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 1, 2023
CompletedFirst Posted
Study publicly available on registry
June 2, 2023
CompletedStudy Start
First participant enrolled
January 23, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 31, 2026
May 4, 2026
February 1, 2026
2.8 years
June 1, 2023
May 1, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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 from the date of randomization to the first objective documentation of disease progression or death due to any cause, assessed up to 2 years
Secondary Outcomes (3)
Objective response
At week 12 and end of treatment
Duration of response
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)
Time from the date of randomization to death due to any cause, assessed up to 2 years
Other Outcomes (6)
CD20 expression
Assessed up to 2 years
Molecular effects of mosunetuzumab and rituximab on tumor cells and the immune response
Assessed up to 2 years
Tumor microenvironment and peripheral immune status
Assessed up to 2 years
- +3 more other outcomes
Study Arms (2)
Arm I (Mosunetuzumab)
EXPERIMENTALPatients receive mosunetuzumab 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 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 (Rituximab, Rituximab and hyaluronidase human)
ACTIVE COMPARATORPatients receive rituximab 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.
Interventions
Receive FDG
Given SC
Given SC
Undergo PET/CT
Undergo tissue biopsy
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo PET/CT
Given IV
Eligibility Criteria
You may qualify if:
- Histopathologically confirmed diagnosis of NLPHL as confirmed by local pathologist's expert review.
- Untreated NLPHL: stage IB to IV according to Cotswolds. The proportion of patients with stages I or II treated with consolidative radiotherapy will be capped at 40%.
- Previously treated NLPHL, any stage.
- According to the treating physician, the patient should not be observed and needs therapy, notably because of B-symptoms (unexplained fever \[temperature \> 38 degrees Celsius (\> 100.4 degrees Fahrenheit)\], weight loss \[unexplained loss of \> 10 percent of body weight over the past six months\], or drenching night sweats), symptomatic nodal or extranodal disease, or patient preferences.
- Patients must have measurable disease according to the Lugano/Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) classification.
- Age \>= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of mosunetuzumab in patients \< 18 years of age, children are excluded from this study.
- Eastern Cooperative Oncology Group performance status =\< 2 (Karnofsky \>= 60%).
- Absolute neutrophil count \>= 1,000/mcL.
- Platelets \>= 100,000/mcL.
- Total bilirubin =\< 1.5 institutional upper limit of normal (ULN), except in patients with Gilbert's syndrome as defined by \> 80% unconjugated bilirubin.
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine transaminase (ALT)(serum glutamic-pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN.
- Glomerular filtration rate (GFR) \>= 40mL /min= GFR (mL/Min/1.73 m\^2) \* body surface area (BSA)/1.73.
- Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- +4 more criteria
You may not qualify if:
- Classical Hodgkin lymphoma (cHL) or composite lymphoma.
- Transformed NLPHL, concerns of the treating physician of an occult transformation or concerns of the treating physician that the patient needs cytotoxic therapy.
- NLPHL relapse less than 6 months after rituximab or rituximab-containing therapy.
- Patients who have not recovered from AEs due to prior anticancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia.
- Patients who are receiving any other investigational agents.
- Patients with central nervous system (CNS) involvement as a result of lymphoma.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to mosunetuzumab or rituximab.
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous.
- Pregnant women are excluded from this study because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with mosunetuzumab; breastfeeding should be discontinued if the mother is treated with mosunetuzumab or rituximab. These potential risks may also apply to other agents used in this study.
- Prior allogeneic stem cell or solid organ transplantation.
- Participants who have received a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live, attenuated vaccine will be required during the study. Participants must not receive live, attenuated vaccines (e.g., FluMist \[registered trademark\]) while receiving study treatment and after the last dose until B-cell recovery to the normal ranges. Killed vaccines or toxoids should be given at least 4 weeks prior to the first dose of study treatment to allow development of sufficient immunity.
- Any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to initiation of study treatment.
- Evidence of any significant, concomitant disease that could affect compliance with the protocol or interpretation of results as judged by the investigator, including, but not limited to:
- Significant cardiovascular disease (e.g., New York Heart Association class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina).
- Significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm).
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (36)
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
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
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D 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
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Raphael E Steiner
University of Texas MD Anderson Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 1, 2023
First Posted
June 2, 2023
Study Start
January 23, 2024
Primary Completion (Estimated)
October 31, 2026
Study Completion (Estimated)
October 31, 2026
Last Updated
May 4, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."