Ann Arbor Stage II Follicular Lymphoma, Ann Arbor Stage III Follicular Lymphoma, Ann Arbor Stage III Marginal Zone Lymphoma, Ann Arbor Stage II 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
Conditions
Brief 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.
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.
Interventions
PROCEDUREBiospecimen Collection
Undergo blood, oral, and/or rectal sample collection
PROCEDUREComputed Tomography
Undergo PET/CT or CT
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
BIOLOGICALMosunetuzumab
Given IV
PROCEDUREPositron Emission Tomography
Undergo PET/CT
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response (OR) | Up to week 13 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AE's) | Up to 30 days after last dose of study treatment | 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. |
| Incidence of grade 3 or greater cytokine release syndrome (CRS) | Up to 30 days after last dose of study treatment | CRS will be graded by the American Society for Transplantation and Cellular Therapy Consensus Grading system. |
| Incidence of Immune Effector Cell Associated Neurotoxicity syndrome | Up to 30 days after last dose of study treatment | — |
| Progression free survival (PFS) | At initiation of study treatment to disease progression, up to 5 years | Kaplan-Meier methodology will be used to estimate PFS. |
| Duration of response | Up to 5 years | — |
| Time to next lymphoma treatment | At initiation of study treatment to initiation of next therapy, up to 5 years | Kaplan-Meier methodology will be used to estimate time to next lymphoma treatment. |
| Time to cytotoxic treatment | At initiation of study treatment to initiation of cytotoxic treatment, up to 5 years | Kaplan-Meier methodology will be used to estimate time to cytotoxic treatment. |
Countries
United States
Contacts
CONTACTAjay Gopal
PRINCIPAL_INVESTIGATORAjay Gopal
Fred Hutch/University of Washington Cancer Consortium
Outcome results
None listed