This phase II trial studies how well ibrutinib in combination with rituximab and lenalidomide works in treating patients with previously untreated, stage II-IV follicular lymphoma or marginal zone lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving ibrutinib in combination with rituximab and lenalidomide may work better in treating follicular lymphoma or marginal zone lymphoma.
PRIMARY OBJECTIVES: I. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated follicular lymphoma (FL) and marginal zone lymphoma (determined by progression-free survival at 2 years). SECONDARY OBJECTIVES: I. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in subjects with FL as assessed by complete response rate (CR) at 120 weeks, overall response rate (ORR), duration of response (DOR), event free survival (EFS), time to next anti-lymphoma treatment (TTNT), and overall survival (OS). II. To evaluate the safety and tolerability of ibrutinib combined with rituximab and lenalidomide in previously untreated subjects with FL and marginal zone lymphoma. EXPLORATORY OBJECTIVES: I. To evaluate prognostic and mechanistic biomarkers relative to treatment outcomes. OUTLINE: Patients receive lenalidomide orally (PO) on days 1-21, rituximab intravenously (IV) over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for 1 year and then every 24 weeks for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
M D Anderson Cancer Center
Houston, Texas, United States
Progression Free Survival (PFS)
Evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated FL and marginal zone lymphoma (determined by PFS at 2 years). Response will be assessed by the investigator based on the 2014 Cheson Lugano criteria. The 2-year PFS rate will be calculated and corresponding 95% confidence interval (CI) will be derived. Kaplan-Meier method will be used to estimate the PFS. Corresponding 95% CI will be summarized. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on time-to-event endpoints.
Time frame: 24 months
Complete Response (CR) Rate
Will be defined as the percentage of participants with a CR at 120 weeks as determined by the principal investigator (Cheson, Lugano classification 2014).
Time frame: At 120 weeks
Overall Response Rate (ORR) (CR Rate + Partial Response [PR])
Will be defined as the percentage of participants with an ORR and assessed by the investigator based on Cheson, Lugano 2014. The best ORR will be recorded.
Time frame: Up to 3 years
Duration of Response (DOR)
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
Time frame: Time by which measurement criteria for CR rate or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented; assessed up to 71.2 months
Event Free Survival (EFS)
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
Time frame: From the date of course 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death; assessed up to 70.2 months
Time to Next Anti-lymphoma Treatment (TTNT)
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
Time frame: From the date of course 1, day 1 to the date of first documented administration of any anti-lymphoma treatment (chemotherapy, radiotherapy, immune therapy, radioimmunotherapy, or other experimental therapy); assessed up to 75.8 months
Overall Survival (OS) Rate
Secondary endpoints included best and 120 week complete response rate (CRR) and ORR by Lugano classification, duration of response, event free survival, time to next anti-lymphoma treatment, overall survival (OS) and safety. Response evaluation was performed at cycle 4, day 1, cycle 7 day 1, at the end of cycle 12, then every 12 weeks for the first four assessments, then every 24 weeks until disease progression
Time frame: From the date of course 1, day 1 to the date of death regardless of cause; assessed up to 78 months
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