This phase II trial studies how well obinutuzumab, ibrutinib, and venetoclax work in treating patients with previously untreated stage II-IV follicular lymphoma. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Ibrutinib and venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving obinutuzumab, ibrutinib, and venetoclax together may work better in treating follicular lymphoma compared to each drug alone.
PRIMARY OBJECTIVE: I. To evaluate the efficacy of obinutuzumab combined with venetoclax and ibrutinib in patients with previously untreated follicular lymphoma (FL) (determined by a positron emission tomography \[PET\]/computed tomography \[CT\] complete response \[CR\] rate at 12 months as per International Workshop Lymphoma Response Criteria, Cheson 2014). SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of obinutuzumab in combination with venetoclax and ibrutinib in patients with untreated FL as assessed by frequency, severity, and relatedness of treatment-emergent adverse events (AEs) as well as frequency of treatment-emergent AEs requiring discontinuation or dose reduction of study drug. II. To evaluate the efficacy of obinutuzumab in combination with venetoclax and ibrutinib in subjects with untreated FL as assessed by CR at 30 months, overall response rate (ORR) (CR + partial response \[PR\]), duration of response (DOR), time to next anti-lymphoma treatment (TTNT), progression-free survival (PFS), and OS. OUTLINE: Patients receive obinutuzumab intravenously (IV) over 60 minutes on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, 8, 10, 12, 14, 16, 18, 20, 22, and 24. Patients also receive venetoclax orally (PO) once daily (QD) on days 1-28 (days 4-28 of cycle 1) and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
University of California, San Francisco (UCSF) Fresno
Fresno, California, United States
RECRUITINGUniversity of California, Los Angeles
Los Angeles, California, United States
NOT_YET_RECRUITINGUniversity of California Davis Comprehensive Cancer Center
Sacramento, California, United States
RECRUITINGUniversity of California, San Diego
San Diego, California, United States
RECRUITINGComplete response (CR) rate
Determined by positron emission tomography (PET)/computed tomography (CT) based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.
Time frame: At 12 months
Frequency, severity, and relatedness of treatment-emergent adverse events (AEs)
Adverse events will be graded and recorded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicity data by type and severity will be summarized by frequency tables.
Time frame: Up to 30 days after completion of study treatment
Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions
Adverse events will be graded and recorded according to NCI CTCAE version 5.0. Toxicity data by type and severity will be summarized by frequency tables.
Time frame: Up to 30 days after completion of study treatment
CR rate
Determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate. The number and percentage of subjects with a CR will be tabulated.
Time frame: At 30 months (120 weeks)
Overall response rate (ORR)
CR + partial response (PR), determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate. The number and percentage of subjects with an ORR will be tabulated. The best ORR will be recorded.
Time frame: Up to 2 years after completion of study treatment
Duration of response
CR + PR, determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval (CI).
Time frame: From the time by which measurement criteria for CR or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 2 years after completion of study treatment
Time to next anti-lymphoma treatment
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI. Comparison by important subgroups will be made using the log-rank test.
Time frame: From the date of cycle 1/day 1 (each cycle is 28 days) to the date of first documented new anti-lymphoma treatment or death from any cause, assessed up to 2 years after completion of study treatment
Progression-free survival
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI. Comparison by important subgroups will be made using the log-rank test.
Time frame: From the date of cycle 1/day 1 (each cycle is 28 days) to the date of first documented progression or death, assessed up to 2 years after completion of study treatment
Overall survival
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI. Comparison by important subgroups will be made using the log-rank test.
Time frame: From the date of cycle 1/day 1 (each cycle is 28 days) to the date of death regardless of cause, assessed up to 2 years after completion of study treatment
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