Recruiting
Phase 2

Rituximab vs. Mosunetuzumab

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05886036

Conditions

Nodular Lymphocyte Predominant B-Cell Lymphoma

Recurrent Nodular Lymphocyte Predominant B-Cell Lymphoma

Refractory Nodular Lymphocyte Predominant B-Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Bone Marrow Biopsy

Computed Tomography

Fludeoxyglucose F-18

Study Details

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.

Conditions

Nodular Lymphocyte Predominant B-Cell Lymphoma

Recurrent Nodular Lymphocyte Predominant B-Cell Lymphoma

Refractory Nodular Lymphocyte Predominant B-Cell Lymphoma

Study ID

NCT05886036

Start date

Jan 23, 2024

Status verified date

Aug, 2026

Completion date

Oct 31, 2026

Anticipated

Primary completion date

Oct 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
  • The effects of mosunetuzumab on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal and/or barrier method of birth control; abstinence) (both hormonal and barrier method of birth control are required for participants in Canada) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of mosunetuzumab administration and 12 months after completion of rituximab administration.
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

  • Classical Hodgkin lymphoma (cHL) or composite lymphoma.
  • Active transformed NLPHL, concerns of the treating physician of an active occult transformation or concerns of the treating physician that the patient needs cytotoxic therapy. Participants with a history of transformed NLPHL in complete remission for at least 2 years since completion of cytotoxic therapy are eligible
  • 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).
  • Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
  • Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 1 year and have no residual neurologic deficits as judged by the investigator are allowed.
  • Participants with a history of epilepsy who have had no seizures in the past 2 years with or without anti-epileptic medications can be eligible only for the expansion cohort.
  • History of confirmed progressive multifocal leukoencephalopathy (PML).
  • Participants with infections requiring IV treatment with antibiotics or hospitalization (grade 3 or 4) within the last 4 weeks prior to enrollment or known active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment.
  • Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to first dose of study treatment.
  • Known or suspected chronic active Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection.
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).

Study Design

Enrollment

70 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (Mosunetuzumab)

Patients 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.

active comparator: Arm II (Rituximab, Rituximab and hyaluronidase human)

Patients 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

Biopsy Procedure

Undergo tissue biopsy

Biospecimen Collection

Undergo blood sample collection

Bone Marrow Biopsy

Undergo bone marrow biopsy

Computed Tomography

Undergo PET/CT

Fludeoxyglucose F-18

Receive FDG

Mosunetuzumab

Given SC

Positron Emission Tomography

Undergo PET/CT

Rituximab

Given IV

Rituximab and Hyaluronidase Human

Given SC

Primary outcome measure

  • Progression-free survival (PFS) time [ 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 ]

Central Contacts and Locations

Locations

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Contacts

Site Public Contact

800-826-4673becomingapatient@coh.org

Principal Investigator:

Alex F. Herrera

UM Sylvester Comprehensive Cancer Center at Aventura

Recruiting

Aventura, Florida, United States, 33180

Contacts

Site Public Contact

954-461-2180

Principal Investigator:

Michele Stanchina

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Michele Stanchina

UM Sylvester Comprehensive Cancer Center at Coral Springs

Recruiting

Coral Springs, Florida, United States, 33065

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Michele Stanchina

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Michele Stanchina

UM Sylvester Comprehensive Cancer Center at Doral

Recruiting

Doral, Florida, United States, 33166

Contacts

Site Public Contact

kginnity@med.miami.edu

Principal Investigator:

Michele Stanchina

UM Sylvester Comprehensive Cancer Center at Hollywood

Recruiting

Hollywood, Florida, United States, 33021

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Michele Stanchina

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Michele Stanchina

UM Sylvester Comprehensive Cancer Center at Kendall

Recruiting

Miami, Florida, United States, 33176

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Michele Stanchina

University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

Recruiting

North Miami, Florida, United States, 33181

Contacts

Site Public Contact

kginnity@med.miami.edu

Principal Investigator:

Michele Stanchina

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Michele Stanchina

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Marc S. Hoffmann

University of Kansas Cancer Center-Overland Park

Recruiting

Overland Park, Kansas, United States, 66210

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Marc S. Hoffmann

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Marc S. Hoffmann

University of Kansas Cancer Center - Briarcliff

Recruiting

Kansas City, Missouri, United States, 64116

Contacts

Site Public Contact

913-588-3671

Principal Investigator:

Marc S. Hoffmann

University of Kansas Cancer Center - North

Recruiting

Kansas City, Missouri, United States, 64154

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Marc S. Hoffmann

University of Kansas Cancer Center - Lee's Summit

Recruiting

Lee's Summit, Missouri, United States, 64064

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Marc S. Hoffmann

Memorial Sloan Kettering Basking Ridge

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Raphael E. Steiner

Memorial Sloan Kettering Monmouth

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Raphael E. Steiner

Memorial Sloan Kettering Bergen

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Raphael E. Steiner

Memorial Sloan Kettering Commack

Recruiting

Commack, New York, United States, 11725

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Raphael E. Steiner

Memorial Sloan Kettering Westchester

Recruiting

Harrison, New York, United States, 10604

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Raphael E. Steiner

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Raphael E. Steiner

Memorial Sloan Kettering Nassau

Recruiting

Uniondale, New York, United States, 11553

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Raphael E. Steiner

Wake Forest University Health Sciences

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Site Public Contact

336-713-6771

Principal Investigator:

Rakhee Vaidya

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Zulfa Omer

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

Yun Choi

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Zulfa Omer

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777ou-clinical-trials@ouhsc.edu

Principal Investigator:

Sami Ibrahimi

UT MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Site Public Contact

866-632-6789askmdanderson@mdanderson.org

Principal Investigator:

Dai Chihara

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100cancerinfo@hci.utah.edu

Principal Investigator:

Allison Bock

University of Virginia Cancer Center

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Site Public Contact

434-243-6303uvacancertrials@hscmail.mcc.virginia.edu

Principal Investigator:

Nathan L. Roberts

VCU Massey Comprehensive Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Site Public Contact

804-628-6430CTOclinops@vcu.edu

Principal Investigator:

Bruce O. Hough

University Health Network-Princess Margaret Hospital

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Site Public Contact

416-946-4501clinical.trials@uhn.on.ca

Principal Investigator:

Anca Prica

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 31, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-31.