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

Grade 3a Follicular Lymphoma Clinical Trial

Official title:

Low Dose Mosunetuzumab for Indolent B-Cell Lymphoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06442475
• Other study ID #: RG1124175
• Secondary ID: NCI-2024-0228920
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 1, 2024
• Est. completion date: February 12, 2027

Study information

• Verified date: June 2024
• Source: University of Washington
• Contact: Ajay Gopal
• Phone: 206-606-2037
• Email: agopal[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: February 12, 2027
• Est. primary completion date: August 12, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ann Arbor Stage II Follicular Lymphoma
• Ann Arbor Stage II Marginal Zone Lymphoma
• Ann Arbor Stage III Follicular Lymphoma
• Ann Arbor Stage III Marginal Zone Lymphoma
• Ann Arbor Stage IV Follicular Lymphoma
• Ann Arbor Stage IV Marginal Zone Lymphoma
• Grade 1 Follicular Lymphoma
• Grade 2 Follicular Lymphoma
• Grade 3a Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular

Intervention

Procedure:
• Biospecimen Collection
Undergo blood, oral, and/or rectal sample collection
• Computed Tomography
Undergo PET/CT or CT
• Magnetic Resonance Imaging
Undergo MRI

Biological:
• Mosunetuzumab
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET/CT

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Incidence of Immune Effector Cell Associated Neurotoxicity syndrome		Up to 30 days after last dose of study treatment
Secondary	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
Secondary	Duration of response		Up to 5 years
Secondary	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
Secondary	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