Lymphoma EZH-302

A Phase 1b/3 Double-Blind, Randomized, Active-Controlled, 3-Stage, Biomarker Adaptive Study Of Tazemetostat Or Placebo In Combination With Lenalidomide Plus Rituximab In Subjects With Relapsed/Refractory Follicular Lymphoma

Stage 1 is a safety run-in phase, stage 2 is an efficacy and safety phase for an assessment of the EZH2 Mutant Type population and overall FL population regardless of EZH2 mutation status, and optional stage 3 with efficacy and safety phase for subjects with EZH2 mutation. Stage 3 with Mutant Type population alone will be executed in case the efficacy of the overall population in stage 2 fails whilst the efficacy of EZH2 Mutant Type is sufficiently promising. Stage 2 will include 2 futility interim analyses based on ORR for the first futility and PFS for the second one. In addition, there is a possible sample size re-estimation based on PFS. This is to ensure early detection of the presence/absence of clinical efficacy benefit as well as ensuring adequate powering based on the trial results to demonstrate a meaningful efficacy difference.

Eligibility Criteria:

  1. Subjects with a history of hepatitis B or C are eligible on the condition that subjects have adequate liver function as defined by Inclusion Criterion #15 and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA.
  2. Have histologically confirmed FL, grades 1 to 3A.
  3. Must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy:
    1. Systemic therapy includes treatments such as:
      1. Rituximab monotherapy ii. Chemotherapy given with or without rituximab iii.  Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab.
    2. Systemic therapy does not include, for example: i. Local involved field radiotherapy for limited-stage disease ii. Helicobacter pylori eradication Prior investigational therapies will be allowed provided the subject has received at least 1 prior systemic therapy as discussed in Inclusion Criteria #6a.
  4. Must have documented relapsed, refractory, or PD after treatment with systemic therapy (refractory defined as less than PR or disease progression <6 months after last dose).

Cancer Clinical Research Office