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Comparing two immunotherapy agents for treating a specific type of lymphoma

NORM: Nodular Lymphocyte-Predominant Hodgkin Lymphoma Patients Treated in a Randomized Phase 2 Trial With Either Rituximab or Mosunetuzumab

Phase 2 Interventional National Cancer Institute (NCI) · NCT05886036

This study is testing whether a new immunotherapy called mosunetuzumab works better than the standard treatment rituximab for people with a specific type of lymphoma.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment70 (estimated)
Ages18 Years and up
SexAll
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionsmosunetuzumab, rituximab, chemotherapy, methotrexate, cyclophosphamide
Locations36 sites (Duarte, California and 35 other locations)
Trial IDNCT05886036 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of mosunetuzumab compared to rituximab in improving progression-free survival in patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Both agents are monoclonal antibodies targeting CD20 on B cells and cancer cells, potentially enhancing the immune response against the lymphoma. The study will assess safety, antitumor activity, and molecular effects on tumor cells and the immune system, utilizing advanced sequencing techniques. Patients will be randomized to receive either treatment, and various biomarkers will be analyzed to understand responses better.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histopathologically confirmed NLPHL, either untreated or previously treated, who require therapy due to symptomatic disease.

Not a fit: Patients with early-stage NLPHL who are asymptomatic and do not require immediate treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with NLPHL, potentially improving survival rates.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific comparison of mosunetuzumab and rituximab is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.
* 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).
  * 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).

Where this trial is running

Duarte, California and 35 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Nodular Lymphocyte Predominant B-Cell LymphomaRecurrent Nodular Lymphocyte Predominant B-Cell LymphomaRefractory Nodular Lymphocyte Predominant B-Cell Lymphoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.