Low Dose Mosunetuzumab for the Treatment of Patients With Indolent B-Cell Lymphoma

Low Dose Mosunetuzumab for Indolent B-Cell Lymphoma

This phase II trial tests the safety, side effects and effectiveness of mosunetuzumab in treating patients with slow growing (indolent) B-cell lymphoma. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread.

Study Overview

• Status: Recruiting
• Conditions: Ann Arbor Stage II Follicular Lymphoma; Ann Arbor Stage III Follicular Lymphoma; Ann Arbor Stage IV Follicular Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Ann Arbor Stage II Marginal Zone Lymphoma; Ann Arbor Stage III Marginal Zone Lymphoma; Ann Arbor Stage IV Marginal Zone Lymphoma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Biological: Mosunetuzumab; Procedure: Biospecimen Collection

Detailed Description

OUTLINE:

Patients receive mosunetuzumab intravenously (IV) over 2-4 hours on days 1, 8, 15 and 22. Patients also undergo blood sample collection and positron emission tomography (PET)/computed tomography (CT) on study. Patients may undergo CT and/or magnetic resonance imaging (MRI) as clinically indicated and may undergo collection of oral and/or rectal swabs on study.

After completion of study treatment, patients are followed up at week 13, at 6 months, and then for up to 5 years per institutional standards.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ajay Gopal; Phone Number: 206-606-2037; Email: agopal@uw.edu

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Principal Investigator: Ajay Gopal
      • Contact: Ajay Gopal; Phone Number: 206-606-2037; Email: agopal@uw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older at time of signing informed consent
• Capable of understanding and providing written informed consent

• Histologically confirmed indolent B-cell non-Hodgkin lymphoma with no prior therapy for lymphoma. (Prior peptide-based therapeutic vaccines are allowed.) Eligible histologies include:

  • Follicular lymphoma (grade 1-2 or 3A)
  • Marginal zone lymphoma
• Ann Arbor stage II-IV disease
• No prior therapy for lymphoma

• Have low-tumor burden disease, defined by Groupe D'Etude des Lymphomes Folliculaires (GELF) criteria:

  • Nodal or extranodal tumor mass < 7 cm
  • Involvement of less than 3 nodal sites with a diameter > 3 cm
  • No systemic or B symptoms
  • No splenomegaly > 16 cm by imaging
  • No local risk of vital organ compression
  • No pleural or peritoneal serous effusions
  • No leukemic phase (> 5,0000/ uL circulating lymphocytes)
  • No significant cytopenias defined as platelets < 100,000/uL, hemoglobin < 10 g/dL, or absolute neutrophil count (ANC) < 1500/ uL
• Have measurable nodal disease, including at least 1 disease site measuring at least 1.5 cm in longest dimension on CT or fludeoxyglucose F-18 (FDG)-PET, or a FDG-avid extranodal measurable site measuring at least 1.0 cm in longest dimension. Measurable disease also includes spleen size more than 13 cm in vertical length
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault equation
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), except in patients with Gilbert's syndrome who may have a total bilirubin up to ≤ 3 x ULN
• Aspartate aminotransferase (AST) ≤ 3 x the ULN
• Alanine aminotransferase (ALT) ≤ 3 x the ULN
• Gamma glutamyl transferase (GGT) ≤ 3 x the ULN
• Negative serum or urine pregnancy test within 7 days of initiating mosunetuzumab for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
• Fertile male and woman of childbearing potential must agree to use highly effective contraceptive methods from start of treatment to at least 3 months after the last dose of mosunetuzumab

Exclusion Criteria:

• History of severe allergic reaction to monoclonal antibody therapy
• History of a second primary malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. Malignancies treated curatively or at low-risk of progressing at the judgment of the principal investigator (PI) may be included
• Known active and uncontrolled bacterial, viral, fungal, mycobacterial, or other infection at study enrollment
• Infection with human immunodeficiency virus (unless viral load is undetectable and CD4 count ≥ 200)

• Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HbBsAg] serology):

  • Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable at the time of screening. These patients must be willing to undergo monthly DNA testing and appropriate antiviral therapy as indicated by institutional standards
• Autoimmune disease requiring active therapy
• History of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
• Evidence of significant concurrent disease or medical condition that could interfere with the conduct of the study, or put the patient at significant risk including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association class III or IV cardiac disease, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
• Ongoing systemic corticosteroid treatment, with the exception of corticosteroid use for other (non-tumor and non-immunosuppressive) indications up to a maximum of 10 mg/day of prednisone or equivalent
• Prior use of any monoclonal antibody within 4 weeks before the first mosunetuzumab administration
• Prior solid organ transplantation
• Pregnant or breast-feeding women, or intending to become pregnant during the study or within 3 months of the last dose of mosunetuzumab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (mosunetuzumab); Patients receive mosunetuzumab IV over 2-4 hours on days 1, 8, 15 and 22. Patients also undergo blood sample collection and PET/CT on study. Patients may undergo CT and/or MRI as clinically indicated and may undergo collection of oral and/or rectal swabs on study.

Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo PET/CT or CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Biological: Mosunetuzumab; Given IV; Other Names: RO7030816; BTCT4465A; Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A; BTCT 4465A; BTCT-4465A; CD20/CD3 BiMAb BTCT4465A; RG 7828; RG-7828; RG7828; Lunsumio; Mosunetuzumab-axgb; Procedure: Biospecimen Collection; Undergo blood, oral, and/or rectal sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response (OR)	OR will be defined as complete response and partial response at the end of therapy based on the latest version of Lugano criteria. Response rates will be calculated using simple binomial proportions and the corresponding 95% confidence interval will be derived.	Up to week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response		Up to 5 years
Incidence of adverse events (AE's)	All AEs will be graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. AEs will be summarized by type, severity, duration, and attribution.	Up to 30 days after last dose of study treatment
Incidence of grade 3 or greater cytokine release syndrome (CRS)	CRS will be graded by the American Society for Transplantation and Cellular Therapy Consensus Grading system.	Up to 30 days after last dose of study treatment
Incidence of Immune Effector Cell Associated Neurotoxicity syndrome		Up to 30 days after last dose of study treatment
Progression free survival (PFS)	Kaplan-Meier methodology will be used to estimate PFS.	At initiation of study treatment to disease progression, up to 5 years
Time to next lymphoma treatment	Kaplan-Meier methodology will be used to estimate time to next lymphoma treatment.	At initiation of study treatment to initiation of next therapy, up to 5 years
Time to cytotoxic treatment	Kaplan-Meier methodology will be used to estimate time to cytotoxic treatment.	At initiation of study treatment to initiation of cytotoxic treatment, up to 5 years

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Ajay Gopal, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2024
• Primary Completion (Estimated): August 12, 2027
• Study Completion (Estimated): February 12, 2028

Study Registration Dates

• First Submitted: May 29, 2024
• First Submitted That Met QC Criteria: May 29, 2024
• First Posted (Actual): June 4, 2024

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Spectrum Analysis; Specimen Handling; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: RG1124175; NCI-2024-02289 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 20417 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No