Tazemetostat in Combination With Umbralisib and Ublituximab for the Treatment Relapsed or Refractory Follicular Lymphoma

PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of a regimen combining tazemetostat, umbralisib and ublituximab in patients with relapsed/refractory follicular lymphoma (FL). II. Estimate the overall response rate (ORR) in relapsed/refractory FL patients treated with tazemetostat, umbralisib and ublituximab. SECONDARY OBJECTIVE: I. Estimate the complete response (CR) rate, time to response, duration of response (DOR), overall survival (OS) and event-free survival (EFS) in relapsed/refractory FL patients treated with tazemetostat, umbralisib and ublituximab. EXPLORATORY OBJECTIVES: I. Examine the immune effects of concurrent targeting of PI3K and EZH2 in patients with FL. II. Examine the evolution of tumor genetic profile while on therapy with tazemetostat, umbralisib and ublituximab, as determined by liquid biopsy. OUTLINE: This is a phase I, dose-escalation study of tazemetostat and umbralisib followed by a phase II trials. Patients receive ublituximab intravenously (IV) on days 1, 8, and 15 of cycle 1, day 1 of cycle 2-6, and day 1 of every 3 cycles thereafter. Patients also receive tazemetostat orally (PO) twice daily (BID) umbralisib by PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 6 months for 2 years.