Title
A Single Arm Phase I/II Study of Tazemetostat with Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma

Description
This study is planned as a single arm clinical trial of tazemetostat in combination with bendamustine and rituximab with both a phase I and phase II component. All patients will receive tazemetostat twice daily on days 1-28 in combination with bendamustine 90 mg/m2 IV on days 1 and 2 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles. Following this, patients will receive tazemetostat twice daily on days 1-28 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.

Objective
Primary Objective:
-To assess the CR rate in patients treated with 3 cycles of BR plus tazemetostat followed by 3 cycles of rituximab plus tazemetostat.

Secondary Objectives:
-To estimate the ORR and CR rate after 3 cycles of BR plus tazemetostat.
-To estimate the PFS and OS at 2 years post completion of treatment.

Exploratory Objectives:
-To evaluate the minimal residual disease (MRD) rate throughout study treatment.
-To evaluate EZH2 mutation status and response by mutational status.

Treatment Experimental: Investigational Group
Phase 1:
90 mg/m^2 of bendamustine by IV on Day 1 and 2 of a 28 day cycle (up to 3 Cycles)
375 mg/m^2 of rituximab by IV on Day 1 of a 28 day cycle (up to 3 Cycles)
Participants enrolled in this phase will be given one of 3 different dose levels of tazemetostat along with the drugs above (for up to 3 Cycles). 3 patients will be assigned to the lowest dose level and if the dose is tolerated, 3 more patients will be enrolled one dose level higher. Up to 18 participants being enrolled.
Dose Level 1: 400 mg of tazemetostat orally twice daily
Dose Level 2: 600 mg of tazemetostat orally twice daily
Dose Level 3: 800 mg of tazemetostat orally twice daily

Phase 2:
6 patients from Phase 1 who were treated at the recommended Phase 2 dose will be added to 21 additional patients.
375 mg/m^2 of rituximab through IV on Day 1 of a 28 day cycle (Cycles 1-6)
Tazemetostat orally twice daily of a 28 day cycle (Cycles 1-6)

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record,

Applicable Disease Sites
Lymphoma

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital