This phase III trial studies rituximab and yttrium Y-90 ibritumomab tiuxetan to see how well they work compared to rituximab alone in treating patients with untreated follicular lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radioactive substances linked to monoclonal antibodies can bind to cancer cells and give off radiation which may help kill cancer cells. It is not yet known whether rituximab works better with or without yttrium Y-90 ibritumomab tiuxetan in treating follicular lymphoma.
PRIMARY OBJECTIVE: I. Test the hypothesis that a single dose of Zevalin (yttrium Y-90 ibritumomab tiuxetan) rituximab immunotherapy (RIT) will increase the complete remission (CR) rate over that achieved with standard rituximab in patients with untreated asymptomatic follicular lymphoma (FL). SECONDARY OBJECTIVES: I. Test the hypothesis that Zevalin RIT will improve progression-free survival. II. Test the hypothesis that Zevalin RIT will improve time to next (any) therapy and time to next chemotherapy. CORRELATIVE RESEARCH OBJECTIVES: I. Study the incidence of exon 2 B-cell leukemia/lymphoma 2 protein (bcl2) mutations in patients with asymptomatic follicular lymphoma (AFL). II. Measure regulatory T cells (Tregs) and tissue monocytes in on-study FL tumor tissue. III. Measure serum cytokines and vitamin D at on study and month 6. IV. Evaluate beta-2 microglobulin plus lactate dehydrogenase (LDH) score as a prognostic factor. V. Measure absolute lymphocyte count (ALC), absolute monocyte count (AMC), and ALC/AMC ratio at on study and after treatment. VI. Compare quality of life as measured by the Functional Assessment of Cancer Therapy (FACT)-Lymphoma (Lym) between arms. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive rituximab intravenously (IV) on days 1, 8, 15, and 22. ARM B: Patients receive rituximab IV on days 1 and 8 and yttrium Y-90 ibritumomab tiuxetan over 10 minutes on day 8. After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months and then every 12 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Complete Response (CR) Rate at the 6-month Disease Assessment
Will be compared between the two arms. The percentage of patients in each response category (e.g., CR, partial remission, stable disease, relapse/progressive disease) will also be tabulated by arm. The proportion of patients who have a CR at 6 months will be evaluated and compared between the two treatment regimens using a two-sided alpha=0.05 continuity corrected Cochran-Mantel-Haenszel test with stratification factors.
Time frame: 6 months
Progression-free Survival (PFS)
The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier within each arm and compared between the arms using a logrank test. The progression-free survival rates at 3 years and 5 years will be estimated in each arm.
Time frame: Time from registration to the earliest date documentation of disease progression or death due to any cause, assessed up to 5 years
Time to Any Therapy (TTNT)
The distribution of time to any therapy will be estimated using the method of Kaplan-Meier within each arm and compared between the arms using a log-rank test. The percentage of patients free of any therapy at 3 years and 5 years will be estimated in each arm.
Time frame: Time from registration to the date of initiation of any treatment for follicular lymphoma, assessed up to 5 years
Time to Chemotherapy (TTC)
The distribution of time to chemotherapy will be estimated using the method of Kaplan-Meier within each arm and compared between the arms using a log-rank test. The percentage of patients free of chemotherapy at 3 years and 5 years will be estimated in each arm.
Time frame: Time from registration to the date of initiation of chemotherapy for follicular lymphoma, assessed up to 5 years
Incidence of Adverse Events
Assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates of individual adverse events (grade 3 and higher) will be compared between arms using a Fisher's exact test.
Time frame: Up to 5 years
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