Study of Tazemetostat Versus Placebo When Given in Combination With Lenalidomide and Rituximab in Participants With Relapsed/Refractory Follicular Lymphoma (SYMPHONY-1)

April 18, 2024 updated by: Epizyme, Inc.

Symphony-1: 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

The participants of this study would have relapsed/refractory follicular lymphoma.

Follicular lymphoma is a type of blood cancer. It is referred to as 'relapsed' when the disease has come back after treatment and 'refractory' when treatment no longer works.

Stage 1 of this trial will study the safety and the level that adverse effects of each of the study drug combinations can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for stage 2 and 3.

Stage 2 and 3 will evaluate and compare how long participants live without their disease getting worse when receiving the study drug in combination with other drug treatment versus the placebo (dummy drug) in combination with other drug treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

612

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Ipsen Clinical Study Enquiries
Phone Number: See e mail
Email: clinical.trials@ipsen.com

Study Locations

Australia
- South Australia
  - Adelaide, South Australia, Australia, 5000
    - Recruiting
    - Royal Adelaide Hospital
    - Contact:
      
      Uwe Hahn, MD
  - Bedford Park, South Australia, Australia, 5042
    - Recruiting
    - Flinders Medical Centre
    - Contact:
      
      Lee Hui-Peng, MD
- Victoria
  - Clayton, Victoria, Australia, 3168
    - Recruiting
    - Monash Health
    - Contact:
      
      Stephen Opat, MD
  - Geelong, Victoria, Australia, 3220
    - Recruiting
    - Barwon Health, University Hospital Geelong
    - Contact:
      
      Philip Campbell, MD
- Western Australia
  - Nedlands, Western Australia, Australia, 6009
    - Recruiting
    - Hollywood Private Hospital
    - Contact:
      
      Chan Yoon Cheah, MD
Belgium
- Namur
  - Yvoir, Namur, Belgium, 5530
    - Withdrawn
    - CHU Dinant Godinne UCL Namur
- Oost-Vlaanderen
  - Gent, Oost-Vlaanderen, Belgium, 9000
    - Recruiting
    - Universitair Ziekenhuis Gent
    - Contact:
      
      Fritz Offner, MD
- Vlaams Brabant
  - Leuven, Vlaams Brabant, Belgium, 3000
    - Recruiting
    - UZ Leuven - Campus Gasthuisberg
    - Contact:
      
      Ann Janssens, MD
Canada
- Ontario
  - Toronto, Ontario, Canada, M5G 2M9
    - Recruiting
    - University Health Network Princess Margaret Hospital
    - Contact:
      
      Michael Crump, MD
- Quebec
  - Montréal, Quebec, Canada, H2X 3E4
    - Recruiting
    - Centre Hospitalier de l'Université de Montréal (CHUM)
    - Contact:
      
      Stephane Doucet, MD
  - Montréal, Quebec, Canada, H3T 1E2
    - Recruiting
    - Sir Mortimer B Davis/Jewish General Hospital
    - Contact:
      
      Nathalie Johnson, MD
China
- - Beijing, China, 100191
    - Recruiting
    - Peking University Third Hospital
    - Contact:
      
      Hongmei Jing, MD
  - Tianjin, China, 300060
    - Recruiting
    - Tianjin Medical University Cancer Institute & Hospital
    - Contact:
      
      Zhengzi Qian, MD
- Fujian
  - Fuzhou, Fujian, China, 350001
    - Recruiting
    - Fujian Medical University Union Hospital
    - Contact:
      
      Jianzhen Shen, MD
  - Xiamen, Fujian, China, 361003
    - Recruiting
    - The First Affiliated Hospital of Xiamen University
    - Contact:
      
      Bing Xu, MD
- Guizhou
  - Guiyang, Guizhou, China, 550004
    - Recruiting
    - The Affiliated Hospital of Guizhou Medical University
    - Contact:
      
      Jishi Wang, MD
- Hangzhou
  - Zhejiang, Hangzhou, China, 310000
    - Recruiting
    - The Second Affiliated Hospital Zhejiang University School of Medicine
    - Contact:
      
      Wenbin Qian, MD
- Hebei
  - Shijiazhuang, Hebei, China, 050011
    - Recruiting
    - The Fourth Hospital of Hebei Medical University
    - Contact:
      
      Lihong Liu
- Henan
  - Zhengzhou, Henan, China, 450008
    - Recruiting
    - Henan Provincial People's Hospital
    - Contact:
      
      Zunmin Zhu, MD
  - Zhengzhou, Henan, China, 45008
    - Recruiting
    - Henan Cancer Hospital
    - Contact:
      
      Yufu Li, MD
- Hunan
  - Changsha, Hunan, China, 410013
    - Recruiting
    - Hunan Cancer Hospital
    - Contact:
      
      Hui Zhou, MD
- Jinlin
  - Changchun, Jinlin, China, 130021
    - Recruiting
    - The First Bethune Hospital of Jilin University
    - Contact:
      
      Ou Bai, MD
- Shandong
  - Qingdao, Shandong, China, 266071
    - Recruiting
    - The Affiliated Hospital of Qingdao University
    - Contact:
      
      Hongwei Xue, MD
- Shanghai
  - Shanghai, Shanghai, China, 20025
    - Recruiting
    - Ruijin Hospital, Shanghai Jiaotong University School Of Medicine
    - Contact:
      
      Weili Zhao, MD
- Shanxi
  - Taiyuan, Shanxi, China, 30032
    - Recruiting
    - Shanxi Bethune Hospital
    - Contact:
      
      Qinghau Zhang, MD
France
- - Besancon, France, 25000
    - Recruiting
    - CHRU de Besançon- Hopital Jean Minjoz
    - Contact:
      
      Adrien Chauchet, MD
  - Caen, France, 14000
    - Withdrawn
    - CHU Caen
  - Clermont-Ferrand, France, 63000
    - Recruiting
    - CHU de Clermont-Ferrand, site Estaing
    - Contact:
      
      Steven Le Gouill, MD
  - Nantes, France, 44202
    - Recruiting
    - L'Hôpital Privé Confluent
  - Paris, France, 75010
    - Recruiting
    - Hôpital Saint Louis
    - Contact:
      
      Catherine Thieblemont, MD
  - Vandœuvre-lès-Nancy, France, 54511
    - Recruiting
    - CHU de Nancy Brabois
    - Contact:
      
      Pierre Feugier, MD
  - Vannes, France, 56017
    - Recruiting
    - Centre Hospitalier Bretagne Atlantique
    - Contact:
      
      Pascal Godmer, MD
- Aquitaine
  - Pessac Cedex, Aquitaine, France, 33600
    - Recruiting
    - Centre Hospitalier Universitaire de Bordeaux-Hopital du Haut Leveque
    - Contact:
      
      Krimo Bouabdallah, MD
- Bretagne
  - Brest, Bretagne, France, 29609
    - Recruiting
    - CHRU Brest Hôp Morvan
    - Contact:
      
      Adrian Tempescul, MD
- Gironde
  - Bordeaux, Gironde, France, 33000
    - Recruiting
    - Institut Bergonie
    - Contact:
      
      Anna Schmitt, MD
- Haut-Rhin
  - Mulhouse, Haut-Rhin, France, 68100
    - Recruiting
    - Centre Hosp Mulh Hop Emile Muller
    - Contact:
      
      Bernard Drenou, MD
- Haute-Normandie
  - Rouen, Haute-Normandie, France, 76038
    - Recruiting
    - Centre Henri Becquerel
    - Principal Investigator:
      
      Fabrice Jardin, MD
- Haute-Vienne
  - Limoges, Haute-Vienne, France, 87042
    - Recruiting
    - CHU de Limoges Dupuytren
    - Contact:
      
      Julie Abraham, MD
- Isere
  - La Tronche, Isere, France, 38700
    - Recruiting
    - CHU de Grenoble - Hopital Albe
    - Contact:
      
      Sylvain Carras, MD
- Loire-Atlantique
  - Nantes, Loire-Atlantique, France, 44000
    - Recruiting
    - CHU de Nantes - Hematologie
    - Principal Investigator:
      
      Thomas Gastinne, MD
- Nord
  - Lille, Nord, France, 59037
    - Recruiting
    - CHRU de Lille Hop Claude Huriez
    - Contact:
      
      Franck Morschhauser, MD
- Sarthe
  - Le Mans, Sarthe, France, 72000
    - Recruiting
    - Centre Hospitalier Le Mans
    - Contact:
      
      Kamel Laribi, MD
- Île-de-France
  - Créteil, Île-de-France, France, 94010
    - Recruiting
    - Hopital Henri Mondor - Hemopathies Lymphoides
    - Contact:
      
      Corinne Haioun, MD
Germany
- Baden-Württemberg
  - Schwäbisch Hall, Baden-Württemberg, Germany, 74523
    - Recruiting
    - Diakoneo Diak Schwaebisch Hall gGmbH
    - Contact:
      
      Thomas Geer, MD
- Bayern
  - München, Bayern, Germany, 81377
    - Recruiting
    - Klinikum der Universität München AÖR
    - Contact:
      
      Dreyling Martin, MD
  - München, Bayern, Germany, 81675
    - Withdrawn
    - Klinikum rechts der Isar der Technischen Universitat Muenche
- Hessen
  - Mainz, Hessen, Germany, 55131
    - Recruiting
    - Universitätsmedizin Mainz
    - Contact:
      
      Georg Hess, MD
- Nordrhein-Westfalen
  - Bonn, Nordrhein-Westfalen, Germany, 53127
    - Recruiting
    - Universitaetsklinikum Bonn AöR
    - Contact:
      
      Franz-Georg Bauernfeind, MD
  - Moenchengladbach, Nordrhein-Westfalen, Germany, 41063
    - Recruiting
    - Kliniken Maria Hilf GmbH
    - Contact:
      
      Ullrich Graeven, MD
- Schleswig-Holstein
  - Kiel, Schleswig-Holstein, Germany, 24116
    - Recruiting
    - Städt. Krankenhaus Kiel
    - Contact:
      
      Repp Roland, MD
Hungary
- - Budapest, Hungary, 1122
    - Recruiting
    - Országos Onkológiai Intézet
    - Contact:
      
      Tamas Schneider, MD
  - Budapest, Hungary, 1088
    - Recruiting
    - Semmelweis Egyetem Altalanos Orvostudomanyi Kar
    - Contact:
      
      Zsolt Nagy, MD
  - Budapest, Hungary, H-1097
    - Recruiting
    - Dél-Pesti Centrumkórház Orszagos Hematologiai es Infektologiai Intezet
    - Contact:
      
      Gabor Mikala, MD
- Hajdú-Bihar
  - Debrecen, Hajdú-Bihar, Hungary, 4032
    - Recruiting
    - Debreceni Egyetem Klinikai Központ
    - Contact:
      
      Arpad Illes, MD
Italy
- - Brescia, Italy, 25123
    - Recruiting
    - ASST Spedali Civili Di Brescia
    - Contact:
      
      Alessandra Tucci, MD
  - Catania, Italy, 95122
    - Recruiting
    - PO Garibaldi-Nesima, ARNAS Garibaldi
    - Contact:
      
      Ugo Consoli, MD
  - Firenze, Italy, 50134
    - Recruiting
    - AOU Careggi
    - Contact:
      
      Benedetta Puccini, MD
  - Roma, Italy, 00168
    - Recruiting
    - Catholic University Of Sacred Heart
    - Contact:
      
      Stefan Hohaus, MD
  - Terni, Italy, 05100
    - Recruiting
    - Azienda Ospedaliera Santa Maria di Terni
    - Contact:
      
      Anna Marina Liberati, MD
- Campania
  - Napoli, Campania, Italy, 80122
    - Recruiting
    - AOU Federico II
    - Contact:
      
      Fabrizio Pane, MD
- Forli-Cesena
  - Meldola, Forli-Cesena, Italy, 47014
    - Recruiting
    - Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori IRCCS
    - Contact:
      
      Gerardo Musuraca, MD
Korea, Republic of
- Seoul Teugbyeolsi
  - Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
    - Recruiting
    - Seoul National University Hospital
    - Contact:
      
      Junshik 준식 Hong 홍, MD
- Seoul Teugbyeolsi [Seoul-T'ukp
  - Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, Korea, Republic of, 03722
    - Recruiting
    - Severance Hospital, Yonsei University Health System
    - Contact:
      
      Jin Seok Kim, MD
  - Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, Korea, Republic of, 06351
    - Recruiting
    - Samsung Medical Center
    - Contact:
      
      Won Seog Kim, MD
- Seoul Teugbyeolsi [Seoul-T'ukp]
  - Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of, 06591
    - Recruiting
    - The Catholic University of Korea, Seoul St. Mary's Hospital
    - Contact:
      
      Seok-Goo Cho, MD
Poland
- - Katowice, Poland
    - Recruiting
    - Pratia Onkologia Katowice
  - Kraków, Poland, 30-727
    - Recruiting
    - Pratia MCM Krakow
    - Contact:
      
      Wojciech Jurczak, MD
  - Słupsk, Poland, 76-200
    - Recruiting
    - Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
    - Contact:
      
      Wojciech Homenda, MD
  - Torun, Poland, 87-100
    - Recruiting
    - MICS Centrum Medyczne Torun
    - Contact:
      
      Dominik Chraniuk, MD
  - Wroclaw, Poland, 50-367
    - Recruiting
    - Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu
    - Contact:
      
      Tomasz Wrobel, MD
- Mazowieckie
  - Warszawa, Mazowieckie, Poland, 02-781
    - Recruiting
    - Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
    - Contact:
      
      Jan Walewski, MD
- Wielkopolskie
  - Skorzewo, Wielkopolskie, Poland, 60-185
    - Recruiting
    - Centrum Medyczne Pratia Poznan
    - Contact:
      
      Maciej Kazmierczak, MD
Spain
- - Barcelona, Spain, 08003
    - Recruiting
    - Hospital del Mar
    - Contact:
      
      Antonio Salar Silvestre, MD
  - Madrid, Spain, 28046
    - Recruiting
    - Hospital Universitario La Paz
    - Contact:
      
      Miguel Canales Albendea, MD
  - Madrid, Spain, 28031
    - Recruiting
    - Hospital Univ. Infanta Leonor
    - Contact:
      
      José Hernández Rivas, MD
  - Salamanca, Spain, 37007
    - Recruiting
    - Hospital Universitario de Salamanca
    - Contact:
      
      Carmen Norma Gutierrez, MD
  - Sevilla, Spain, 41014
    - Recruiting
    - Hospital Universitario Nuestra Señora de Valme
    - Contact:
      
      Eduardo Ríos Herránz, MD
- Cataluny
  - Barcelona, Cataluny, Spain, 08035
    - Recruiting
    - Hospital Universitari Vall d'Hebron
    - Contact:
      
      Sabela Bobillo, MD
- Málaga
  - Marbella, Málaga, Spain, 29603
    - Recruiting
    - Hospital Costa del Sol
    - Contact:
      
      Maria Espinosa Casanova, MD
Taiwan
- - Kaohsiung, Taiwan, 833
    - Recruiting
    - Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
    - Contact:
      
      Ming-Chung 銘崇 Wang 王, MD
  - Taichung, Taiwan, 40705
    - Recruiting
    - Taichung Veterans General Hospital
    - Contact:
      
      Chieh-Lin Teng, MD
  - Tainan, Taiwan, 704
    - Recruiting
    - National Cheng Kung University Hospital
    - Contact:
      
      Ya-Ting Hsu, MD
  - Taipei, Taiwan
    - Recruiting
    - National Taiwan University Hospital
    - Contact:
      
      Shang-Ju 尚儒 Wu 吳, MD
United Kingdom
- - Glasgow, United Kingdom, G12 0YN
    - Recruiting
    - Beatson West of Scotland Cancer Centre
    - Contact:
      
      Pamela McKay, MD
- Edinburgh, City Of
  - Edinburgh, Edinburgh, City Of, United Kingdom, EH4 2XU
    - Recruiting
    - Western General Hospital - Haematology
    - Contact:
      
      Angus Broom, MD
- London City
  - London, London City, United Kingdom, W12 0HS
    - Recruiting
    - Imperial College Healthcare NHS Trust - Hammersmith Hospital
    - Contact:
      
      Aristeidis Chaidos, MD
- London, City Of
  - London, London, City Of, United Kingdom, EC1A 7BE
    - Recruiting
    - St Bartholomew's Hospital Barts Health NHS Trust
    - Contact:
      
      John Gribben, MD
United States
- Alabama
  - Mobile, Alabama, United States, 36608
    - Recruiting
    - Southern Cancer Center
    - Contact:
      
      Michael Meshad, MD
- Arizona
  - Tucson, Arizona, United States, 85704
    - Recruiting
    - Arizona Oncology Associates - Tuscon-Rusadill Road
    - Contact:
      
      Sudhir Manda, MD
- California
  - Cerritos, California, United States, 90703
    - Recruiting
    - TOI - Clinical Research
    - Principal Investigator:
      
      Omkar Marathe, MD
  - Clovis, California, United States, 93611
    - Recruiting
    - UCSF Fresno
    - Contact:
      
      Haifaa Abdulhaq, MD
  - La Jolla, California, United States, 92093
    - Recruiting
    - UC San Diego Health Sciences
    - Contact:
      
      Benjamin Heyman
  - Santa Monica, California, United States, 90404
    - Recruiting
    - UCLA Clinical Research Unit Hematology/Oncology
    - Contact:
      
      Sven De Vos, MD
- Colorado
  - Boulder, Colorado, United States, 80303
    - Recruiting
    - Rocky Mountain Cancer Centers (RMCC) - Boulder
    - Contact:
      
      David Andorsky, MD
  - Grand Junction, Colorado, United States, 81501
    - Recruiting
    - St. Mary's Hospital and Regional Medical Center - St. Mary's
    - Contact:
      
      Kyle Work, MD
  - Greeley, Colorado, United States, 80033
    - Withdrawn
    - SCL Health Lutheran Medical Center
- Florida
  - Fleming Island, Florida, United States, 32003
    - Recruiting
    - Cancer Specialists of North Florida
    - Contact:
      
      Mehdi M Moezi, MD
  - Fort Myers, Florida, United States, 33908
    - Recruiting
    - Florida Cancer Specialists & Research Institute (FCS) - Fort Myers Cancer Center
    - Contact:
      
      Syed Farhan Zafar, MD
  - Jacksonville, Florida, United States, 32224
    - Recruiting
    - Mayo Clinic
    - Contact:
      
      Tan Han, MD
  - Jacksonville, Florida, United States, 32224
    - Withdrawn
    - Mayo Clinic - Cancer Clinical Research Office
  - Miami, Florida, United States, 33176
    - Withdrawn
    - Miami Cancer Institute
  - Ocala, Florida, United States, 34474
    - Recruiting
    - Florida Cancer Affiliates/Ocala Oncology - Clinic
    - Contact:
      
      Ketan Doshi, MD
  - Plantation, Florida, United States, 33322
    - Recruiting
    - BRCR Medical Center, Inc
    - Contact:
      
      Jason Tache, MD
  - Saint Petersburg, Florida, United States, 33705
    - Recruiting
    - Florida Cancer Specialists
    - Contact:
      
      Sunil Gandhi, MD
  - Tallahassee, Florida, United States, 32308
    - Recruiting
    - Florida Cancer Specialists - Panhandle
    - Principal Investigator:
      
      Viralkumar Bhanderi
  - Tampa, Florida, United States, 33612
    - Recruiting
    - H Lee Moffitt Cancer Center and Research Institute I
    - Contact:
      
      Sameh Gaballa, MD
  - West Palm Beach, Florida, United States, 33401
    - Recruiting
    - Florida Cancer Specialists & Research Institute (FCS) - Atlantis
    - Contact:
      
      Shachar Peles, MD
- Hawaii
  - Honolulu, Hawaii, United States, 96819
    - Withdrawn
    - Kaiser Permanente Hawaii Moanalua Medical Center
- Illinois
  - Chicago, Illinois, United States, 60637
    - Recruiting
    - University of Chicago
    - Contact:
      
      Sonali Smith, MD
  - Niles, Illinois, United States, 60714
    - Recruiting
    - Illinois Cancer Specialists
    - Contact:
      
      Leonard Klein, MD
- Iowa
  - Sioux City, Iowa, United States, 51101
    - Recruiting
    - June E. Nylen Cancer Center
    - Contact:
      
      Donald B Wender, MD
- Kansas
  - Overland Park, Kansas, United States, 66210
    - Withdrawn
    - The University of Kansas Cancer Center
- Maryland
  - Baltimore, Maryland, United States, 21201
    - Withdrawn
    - University of Maryland
  - Chevy Chase, Maryland, United States, 20815-6908
    - Withdrawn
    - The office of Frederick P. Smith, MD, P.C.
- Massachusetts
  - Newton, Massachusetts, United States, 02462
    - Withdrawn
    - Mass General Cancer Center at Newton-Wellesley
- Michigan
  - Ann Arbor, Michigan, United States, 48109
    - Recruiting
    - University of Michigan Comprehensive Cancer Center
    - Contact:
      
      Sano Dahlia, MD
  - Ypsilanti, Michigan, United States, 48197
    - Recruiting
    - St. Joseph Mercy Hospital
    - Contact:
      
      Christopher Reynolds, MD
- Minnesota
  - Rochester, Minnesota, United States, 55901
    - Recruiting
    - Mayo Clinic - Rochester
    - Contact:
      
      Jose C Villasboas Bisneto, MD
- Missouri
  - Saint Louis, Missouri, United States, 63110
    - Recruiting
    - Saint Louis University Cancer Center
    - Contact:
      
      Rajeh Nabeel Mhd, MD
- Nebraska
  - Omaha, Nebraska, United States, 68198
    - Recruiting
    - University of Nebraska Medical Center
    - Contact:
      
      Julie Vose, MD
- New Jersey
  - East Brunswick, New Jersey, United States, 08816
    - Recruiting
    - Astera Cancer Care
    - Contact:
      
      Bruno Fang, MD
  - East Brunswick, New Jersey, United States, 08816
    - Recruiting
    - Astera Cancer Center
    - Contact:
      
      Bruno Fang, MD
  - Freehold, New Jersey, United States, 07728
    - Recruiting
    - Regional Cancer Care Associates-Freehold
    - Contact:
      
      Nandini Ignatius, MD
  - Hackensack, New Jersey, United States, 07601
    - Withdrawn
    - Hackensack University Medical John Theurer Cancer Center
  - Howell, New Jersey, United States, 07731
    - Withdrawn
    - Regional Cancer Care Associates LLC - Howell
  - Little Silver, New Jersey, United States, 07739
    - Recruiting
    - Regional Cancer Care Associates LLC - Little Silver
    - Contact:
      
      Ian Horkheimer, MD
- New Mexico
  - Albuquerque, New Mexico, United States, 87131-0001
    - Recruiting
    - New Mexico Cancer Care Alliance
    - Contact:
      
      Leslie Andritsos, MD
- New York
  - Albany, New York, United States, 12206
    - Withdrawn
    - New York Oncology Hematology, P.C.
  - Lake Success, New York, United States, 11042
    - Recruiting
    - Northwell Health/Monter Cancer Center
    - Contact:
      
      Joanna Rhodes, MD
  - New York, New York, United States, 10065
    - Recruiting
    - Memorial Sloan-Kettering Cancer Center
    - Principal Investigator:
      
      Salles Gilles, MD
  - New York, New York, United States, 10032
    - Recruiting
    - Columbia U - Herbert Irving Comprehensive Cancer Center
    - Contact:
      
      Jennifer Amengual, MD
  - New York, New York, United States, 10021
    - Recruiting
    - Weill Cornell Medicine-New York Presbyterian Hospital
    - Contact:
      
      John P Leonard, MD
  - Nyack, New York, United States, 10960
    - Recruiting
    - Hematology Oncology Associates of Rockland, P.C.
    - Contact:
      
      Sung Ho Lee, MD
- North Carolina
  - Asheville, North Carolina, United States, 28806
    - Recruiting
    - Messino Cancer Center
    - Contact:
      
      Christopher Chay, MD
  - Concord, North Carolina, United States, 28205
    - Recruiting
    - Levine Cancer Institute - Concord
    - Principal Investigator:
      
      Steven Park, MD
  - Pinehurst, North Carolina, United States, 28374
    - Recruiting
    - FirstHealth of the Carolinas
    - Contact:
      
      Charles Kuzma, MD
- Ohio
  - Canton, Ohio, United States, 44718
    - Recruiting
    - Gabrail Cancer Center Research
    - Contact:
      
      Nashat Gabrail, MD
  - Cincinnati, Ohio, United States, 45236
    - Recruiting
    - Oncology Hematology Care (OHC), Inc. - Kenwood Office
    - Contact:
      
      Miguel Islas-Ohlmayer, MD
    - Principal Investigator:
      
      Patel Ameet
- Oregon
  - Eugene, Oregon, United States, 97401
    - Recruiting
    - Willamette Valley Cancer Institute and Research Center - Oncology
    - Contact:
      
      Jeffrey Sharman, MD
- Pennsylvania
  - Pittsburgh, Pennsylvania, United States, 15524
    - Recruiting
    - Western Pennsylvania Hospital Hematology & Cellular Therapy
    - Principal Investigator:
      
      Cyrus M Khan, MD
  - Pittsburgh, Pennsylvania, United States, 15232
    - Withdrawn
    - University of Pittsburgh Medical Center - Oncology
- Tennessee
  - Chattanooga, Tennessee, United States, 37404
    - Withdrawn
    - Tennessee Oncology, PLLC
  - Knoxville, Tennessee, United States, 37920
    - Recruiting
    - University of Tennessee Medical Center - Cancer Institute
    - Contact:
      
      Radhakrishnan Ramchandren, MD
  - Nashville, Tennessee, United States, 37203
    - Recruiting
    - Sarah Cannon Research Institute
    - Principal Investigator:
      
      Ian Flinn
    - Contact:
      
      Viralkumar Bhanderi, MD
- Texas
  - Amarillo, Texas, United States, 79124
    - Recruiting
    - Texas Oncology - Amarillo
    - Contact:
      
      Praveen Tumula, MD
  - Austin, Texas, United States, 78705
    - Recruiting
    - Texas Oncology-Austin Midtown
    - Contact:
      
      Jason M Melear, MD
  - Dallas, Texas, United States, 75246
    - Recruiting
    - Texas Oncology-Baylor Charles A. Sammons Cancer Center
    - Contact:
      
      Moshe Y Levy, MD
  - Dallas, Texas, United States, 75230
    - Recruiting
    - Texas Oncology - Medical City Dallas Pediatric Hematology
    - Contact:
      
      Jay Courtright, MD
  - Houston, Texas, United States, 77030
    - Recruiting
    - The University of Texas MD Anderson Cancer Center
    - Principal Investigator:
      
      Loretta Nastoupil, MD
  - Houston, Texas, United States, 77090
    - Recruiting
    - Millennium Physicians - Oncology
    - Contact:
      
      Charles Yen, MD
  - Plano, Texas, United States, 75075
    - Recruiting
    - Texas Oncology
    - Contact:
      
      Charles Connor, MD
  - San Antonio, Texas, United States, 78229
    - Recruiting
    - Mays Cancer Center
    - Contact:
      
      Adolfo Diaz Duque, MD
  - Tyler, Texas, United States, 75701
    - Recruiting
    - UT Health East Texas HOPE Cancer Center - Tyler
    - Contact:
      
      Arielle S Lee, MD
  - Tyler, Texas, United States, 75702
    - Recruiting
    - USO Texas Oncology - Tyler
    - Contact:
      
      Habte A Yimer, MD
  - Weslaco, Texas, United States, 78596
    - Recruiting
    - Texas Oncology- Weslaco
    - Contact:
      
      Daniel Farray-Berges, MD
- Utah
  - Salt Lake City, Utah, United States, 84106
    - Recruiting
    - Utah Cancer Specialists/ IHO Corp
    - Contact:
      
      Stephan Kendall, MD
  - Salt Lake City, Utah, United States, 84112
    - Recruiting
    - Huntsman Cancer Institute; The University of Utah
    - Contact:
      
      Harsh Shah, MD
- Virginia
  - Chesapeake, Virginia, United States, 23320
    - Withdrawn
    - Peninsula Cancer Institute
  - Gainesville, Virginia, United States, 22155
    - Recruiting
    - Virginia Cancer Specialists
    - Contact:
      
      Mitul Gandhi, MD
  - Roanoke, Virginia, United States, 24014
    - Recruiting
    - Oncology and Hematology Associates of Southwest Virginia Inc.
    - Contact:
      
      Amanda Gillespie-Twardy, MD
- Washington
  - Spokane, Washington, United States, 99218
    - Withdrawn
    - MC Rockwood Cancer Bl Specialty Ctr - North
  - Yakima, Washington, United States, 98902
    - Recruiting
    - Yakima Valley Memorial Hospital - North Star Lodge Cancer Center
    - Contact:
      
      Sri Obulareddy, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Description

Inclusion Criteria:

Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.
Males or females are ≥18 years of age at the time of providing voluntary written informed consent.
Life expectancy ≥3 months before enrollment.
Meet requirement for hepatitis and human immunodeficiency virus (HIV) infection as follows
- Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection Note: Patients whose HBV infection status could not be determined by serologic test results have to be negative for HBV-DNA by PCR to be eligible for study participation. Patients seropositive for HBV with undetectable HBV DNA by PCR are permitted with appropriate antiviral prophylaxis.
- Negative test results for hepatitis C virus (HCV) Note: Patients who are positive for HCV antibody must be negative for HCV RNA by PCR to be eligible for study participation
- If HIV positive, HIV infection is controlled
Have histologically confirmed FL, Grades 1 to 3A.
Must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy:
a. Systemic therapy includes treatments such as:
i. Rituximab monotherapy
ii. Chemotherapy given with or without rituximab
iii. Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab.
b. Systemic therapy does not include, for example:
i. Local involved field radiotherapy for limited-stage disease
ii. Helicobacter pylori eradication
c. Prior investigational therapies will be allowed provided the subject has received at least 1 prior systemic therapy as discussed in Inclusion Criterion #6a.
d. Prior autologous/allogeneic hematopoietic stem cell transplant (HSCT) will be allowed.
e. Prior chimeric antigen receptor T-cell therapy (CAR T) will be allowed.
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).
Have measurable disease as defined by the Lugano Classification (Cheson, 2014; Appendix 5).
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Within 7 days prior to randomization, all clinically significant toxicity related to a prior anticancer treatment (ie, chemotherapy, immunotherapy, and/or radiotherapy must have either resolved to Grade 1 per NCI CTCAE Version 5.0 OR are clinically stable and no longer clinically significant.
Have provided sufficient tumor tissue block or unstained slides for EZH2 mutation testing in all subjects to allow for stratification
a. If EZH2 mutation status is known from site-specific testing, subjects can be enrolled. Tumor tissue will be required for confirmatory testing of EZH2 status at study-specific laboratories. If the archival tumor sample was collected more than 24 months prior to the anticipated administration of the first dose (cycle 1 day 1), then a fresh biopsy must be provided. Fresh tumor biopsy is appropriate except for procedures deemed to result in unacceptable risk because of the anatomical location including brain, lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel. Archival tumor biopsy sections mounted on slides are also acceptable.
NOTE: Confirmatory testing will also be performed for Stage 1, if local EZH2 testing is conducted, unless there is insufficient tumor tissue to perform testing after discussion with the Sponsor's or Designee Medical Monitor.
Time between prior anticancer therapy and first dose of tazemetostat as follows:
1. Cytotoxic chemotherapy - At least 21 days.
2. Noncytotoxic chemotherapy (eg, small molecule inhibitor) - At least 14 days.
3. Nitrosoureas - At least 6 weeks.
4. Monoclonal and/or bispecific antibodies or CAR T - At least 28 days.
5. Radiotherapy - At least 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation.
Adequate renal function defined as calculated creatinine clearance ≥30 mL/minute per the Cockcroft and Gault formula.
Adequate bone marrow function:
a. Absolute neutrophil count (ANC) ≥1000/mm3 (≥1.0 × 10^9/L) if no lymphoma infiltration of bone marrow OR ANC ≥750/mm3 (≥75 × 10^9/L) with bone marrow infiltration
- Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days.
  b. Platelets ≥75,000/mm3 (≥75 × 10^9/L)
- Evaluated at least 7 days after last platelet transfusion.
  c. Hemoglobin ≥9.0 g/dL
- May receive transfusion
Adequate liver function:
1. Total bilirubin ≤1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
2. Alkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if subject has liver infilration).
International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless on warfarin, then INR ≤3.0). In subjects with thromboembolism risk, prophylactic anticoagulation, or antiplatelet therapy at investigator discretion is recommended.
Females of childbearing potential (FCBP) must have a negative urine or serum pregnancy tests (beta-human chorionic gonadotropin [β-hCG] tests with a minimum sensitivity of 25 mIU/mL or equivalent units of β-hCG) at screening within 10 to 14 days prior to first dose of study drug. The subject may not receive study drug until the study doctor has verified that the results of pregnancy tests are negative. All females will be considered to be of childbearing potential unless they are naturally postmenopausal (at least 24 months consecutively amenorrhoeic [amenorrhea following cancer therapy does not rule out childbearing potential] and without other known or suspected cause) or have been sterilized surgically (ie, total hysterectomy and/or bilateral oophorectomy, with surgery completed at least 1 month before dosing).
Females of childbearing potential (FCBP) enrolled must either practice complete abstinence or agree to use two reliable methods of contraception simultaneously. This includes ONE highly effective method of contraception and ONE additional effective contraceptive method. Contraception must begin at least 28 days prior to first dose of study drug, continue during study treatment (including during dose interruptions), and for 12 months after study drug discontinuation. Female subjects must also refrain from breastfeeding for 12 months following last dose of study drug. If the below contraception methods are not appropriate for the FCBP, she must be referred to a qualified contraception provider to determine the medically effective contraception method appropriate for the subject. The following are examples of highly effective and additional effective methods of contraception:
Examples of highly effective methods:
- Intrauterine device (IUD)
- Hormonal (ovulation inhibitory combined [estrogen and progesterone] birth control pills or intravaginal/transdermal system, injections, implants, levonorgestrel-releasing intrauterine system [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills [e.g. desogestrel]) NOTE: There is a potential for tazemetostat interference with hormonal contraception methods due to enzymatic induction.
- Bilateral tubal ligation
- Partner's vasectomy (if medically confirmed [azoospermia] and sole sexual partner).
Examples of additional effective methods:
- Male latex or synthetic condom,
- Diaphragm,
- Cervical Cap
NOTE: Female subjects of childbearing potential exempt from these contraception requirements are subjects who practice complete abstinence from heterosexual sexual contact. True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.
All study participants enrolled must be registered into the applicable pregnancy prevention program (e.g. REVLIMID REMS in the US, Pregnancy Prevention Programme [PPP] in Europe, RevAid in Canada) for lenalidomide to be administered and be willing and able to comply with the requirements of the applicable program as appropriate for the country in which the drug is being used.
a. Female subjects of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing as required in theapplicable pregnancy prevention program. During study treatment, FCBP must agree to have pregnancy testing weekly for the first 28 days of study participation and then every 28 days for FCBP with regular or no menstrual cycles OR every 14 days for FCBP with irregular menstrual cycles. FCBP must also have a pregnancy test at end of lenalidomide treatment, at days 14 and 28 following the last dose of lenalidomide and at overall treatment discontinuation (at the End-of-Treatment/30-day safety Follow-up visit). Female subjects exempt from this requirement are subjects who have been naturally postmenopausal for at least 24 consecutive months OR have had a total hysterectomy and/or bilateral oophorectomy.
Male subjects must either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy (medically confirmed azoospermia), during sexual contact with a pregnant female or FCBP from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.

NOTE: Male subjects must not donate semen or sperm from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.

Exclusion Criteria:

All Subjects

Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
Prior exposure to lenalidomide or drugs of the same class.
Grade 3b, mixed histology, or FL that has histologically transformed to diffuse large B-cell lymphoma (DLBCL) (subjects transformed from DLBCL to FL may be enrolled).
Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE Version 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN).
Has a prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL) or B-cell acute lymphoblastic leukemia (B-ALL).
Subjects with uncontrolled leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
Subjects taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort).
Are unwilling to exclude grapefruit juice, Seville oranges, and grapefruits from the diet and/or consumed within 1 week of the first dose of study drug and for the duration of the study.
Major surgery within 4 weeks before the first dose of study drug.
a. Note: Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment.
Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.
Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia (Appendix 3).
Prolongation of corrected QT interval using Fridericia's formula (QTcF) to ≥480 msec at screening or history of long QT syndrome.
Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.
a. Note: Patients who have experienced deep vein thrombosis/pulmonary embolism more than 3 months before enrollment are eligible but are recommended to receive prophylaxis.
Have an active infection requiring systemic therapy.
Known hypersensitivity to any component of tazemetostat or lenalidomide; known severe hypersensitivity to any component of rituximab requiring hospitalization or resuscitation.
Active viral infection with or seropositive for HBV: HBV surface antigen (HBsAg) positive OR HBsAg negative, anti-HBs positive and/or anti-HBc positive with detectable HBV DNA.
NOTE: Subjects who are HBsAg negative, anti-HBs positive and/or anti-HBc positive, but with undetectable viral DNA and normal ALT are eligible. Subjects who are seropositive due to HBV vaccination (HBsAg negative, HBV surface antibody [anti-HBs] positive, and HBV core antibody [anti-HBc] negative) are eligible.
Active viral infection with hepatitis C virus (as measured by positive HCV antibody and detectable viral RNA, HIV), or known active infection with human T-cell lymphotropic virus.
NOTE: Subjects with a history of hepatitis C infection (HCV antibody reactive) who have normal ALT and undetectable HCV RNA are eligible.
Any other medical or social condition that, in the Investigator's judgment, will interfere with a patient's ability to provide informed consent, to receive study drugs, or meet study demands, or that substantially increases the risk associated with the subject's participation in the study, or that may interfere with interpretation of results.
Female subjects who are pregnant or lactating/breastfeeding.
Subjects who have undergone a solid organ transplant.
Subjects with malignancies other than FL. a. Exception: Subjects with another malignancy who have been disease-free for 3 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Sequential Assignment
Masking: Quadruple

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tazemetostat + R2 arm Stage 1 (Phase 1b): Tazemetostat will be escalated from a starting dose of 400 mg PO twice daily to 600 mg PO twice daily to 800 mg PO twice daily in 28-day cycles. Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or <60 mL/minute), administred PO QD on days 1 to 21 for 12 cycles. Stage 2 and Optional Stage 3 (Phase 3): Tazemetostat 800 mg administered PO twice daily in continuous 28-day cycles. Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or <60 mL/minute), PO QD on days 1 to 21 for 12 cycles. Maintenance Therapy (Stage 1, 2, and Optional Stage 3): Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.	Combination product: Rituximab Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. Drug: Tazemetostat Stage 1 (Phase 1b): Tazemetostat will be escalated from a starting dose of 400 mg orally twice daily to 600 mg orally twice daily to 800 mg PO twice daily in 28-day cycles as tolerated in a standard 3 + 3 design. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy. Other Names: EPZ-6438 IPN60200 Drug: Tazemetostat Stage 2 and Optional Stage 3 (Phase 3): Tazemetostat 800 mg administered orally twice daily in continuous 28-day cycles for 12 cycles. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy. Other Names: EPZ-6438 IPN60200 Combination product: Lenalidomide Lenalidomide 20 mg capsules or 10 mg capsules (if creatinine clearance ≥60 mL/minute or <60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.
Placebo Comparator: Placebo + R2 Arm Stage 2 and Optional Stage 3 (Phase 3): Placebo administered PO twice daily in continuous 28-day cycles. Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or <60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles. Maintenance Therapy (Stage 1, 2, and Optional Stage 3): Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy. During maintenance, placebo will be continued until disease progression or unacceptable toxicity, or participant withdraws consent.	Combination product: Rituximab Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. Combination product: Lenalidomide Lenalidomide 20 mg capsules or 10 mg capsules (if creatinine clearance ≥60 mL/minute or <60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles. Drug: Placebo oral tablet Placebo administered orally twice daily in continuous 28-day cycles. Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Participant Group / Arm

Intervention / Treatment

Experimental: Tazemetostat + R2 arm

Stage 1 (Phase 1b):

Tazemetostat will be escalated from a starting dose of 400 mg PO twice daily to 600 mg PO twice daily to 800 mg PO twice daily in 28-day cycles.
Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or <60 mL/minute), administred PO QD on days 1 to 21 for 12 cycles.

Stage 2 and Optional Stage 3 (Phase 3):

Tazemetostat 800 mg administered PO twice daily in continuous 28-day cycles.
Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or <60 mL/minute), PO QD on days 1 to 21 for 12 cycles.

Maintenance Therapy (Stage 1, 2, and Optional Stage 3):

Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Combination product: Rituximab

Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.

Drug: Tazemetostat

Stage 1 (Phase 1b):

Tazemetostat will be escalated from a starting dose of 400 mg orally twice daily to 600 mg orally twice daily to 800 mg PO twice daily in 28-day cycles as tolerated in a standard 3 + 3 design. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Other Names:

EPZ-6438
IPN60200

Drug: Tazemetostat

Stage 2 and Optional Stage 3 (Phase 3):

Tazemetostat 800 mg administered orally twice daily in continuous 28-day cycles for 12 cycles. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Other Names:

EPZ-6438
IPN60200

Combination product: Lenalidomide

Lenalidomide 20 mg capsules or 10 mg capsules (if creatinine clearance ≥60 mL/minute or <60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.

Placebo Comparator: Placebo + R2 Arm

Stage 2 and Optional Stage 3 (Phase 3):

Placebo administered PO twice daily in continuous 28-day cycles.
Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or <60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.

Maintenance Therapy (Stage 1, 2, and Optional Stage 3):

Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy. During maintenance, placebo will be continued until disease progression or unacceptable toxicity, or participant withdraws consent.

Combination product: Rituximab

Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.

Combination product: Lenalidomide

Lenalidomide 20 mg capsules or 10 mg capsules (if creatinine clearance ≥60 mL/minute or <60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.

Drug: Placebo oral tablet

Placebo administered orally twice daily in continuous 28-day cycles. Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Time Frame: Up to 72 months	PFS is defined as the time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, as assessed by Investigators.	Up to 72 months
Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2) Time Frame: Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 will be selected at the end of Phase 1b	The safety and tolerability of tazemetostat in combination with R2 in subjects with R/R FL will be evaluated. RP3D of tazemetostat for further evaluation in phase 3 will be selected as assessed by the occurrence of treatment-emergent dose-limiting toxicities (DLTs) and adverse events (AEs).	Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 will be selected at the end of Phase 1b

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) Time Frame: up to 100 weeks	OS is defined as the time from the date of randomization until death due to any cause.	up to 100 weeks
Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax). Time Frame: In cycles 1 and 2 on days 1 and 15 (28 days cycle)	Cmax will be recorded from the PK blood samples collected.	In cycles 1 and 2 on days 1 and 15 (28 days cycle)
PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax) Time Frame: In cycles 1 and 2 on days 1 and 15 (28 days cycle)		In cycles 1 and 2 on days 1 and 15 (28 days cycle)
PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration [AUC(0-t)], Time Frame: In cycles 1 and 2 on days 1 and 15 (28 days cycle)		In cycles 1 and 2 on days 1 and 15 (28 days cycle)
PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-∞)] Time Frame: In cycles 1 and 2 on days 1 and 15 (28 days cycle)		In cycles 1 and 2 on days 1 and 15 (28 days cycle)
The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit Time Frame: In cycles 1 and 2 on days 1 and 15 (28 days cycle)		In cycles 1 and 2 on days 1 and 15 (28 days cycle)
PFS Time Frame: Up to 72 months	PFS is defined as the time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, as assessed by blinded independent review committee (IRC).	Up to 72 months
Objective Response Rate (ORR) Time Frame: Up to 72 months	ORR is defined as the proportion of subjects achieving partial response (PR) or complete response (CR) according to the 2014 Lugano Classification as assessed by Investigator and IRC.	Up to 72 months
Duration of response (DOR) Time Frame: Up to 72 months	DOR is defined as the time from initial CR or PR to documented progression or death, whichever occurs first, as assessed by Investigator and IRC.	Up to 72 months
Duration of complete response (DOCR) Time Frame: Up to 72 months	DOCR, defined as the time from initial CR to documented progression or death, whichever occurs first, as assessed by Investigator and IRC.	Up to 72 months
Disease control rate (DCR) Time Frame: Up to 72 months	Disease control rate defined as the proportion of subjects with best overall response of CR, PR, or SD lasting 12 or more months, as assessed by the Investigators and IRC.	Up to 72 months
Quality of life questionnaires evaluation Time Frame: Measured at Screening, on Day 1 and Day 15 of Cycles 1 and 2, on Day 1 and optionally on Day 15 of each cycle from Cycle 3 and beyond, and at end of treatment visit, up to 3 years. (Each cycle is 28 days)	Evaluate and compare health-related quality of life as measured by the EuroQOL 5-Dimension 5-Level (EQ-5D-5L) instrument and the Functional Assessment of Cancer Therapy -Lymphoma (FACT-Lym)	Measured at Screening, on Day 1 and Day 15 of Cycles 1 and 2, on Day 1 and optionally on Day 15 of each cycle from Cycle 3 and beyond, and at end of treatment visit, up to 3 years. (Each cycle is 28 days)
Population PK parameters of oral clearance (CL/F) of tazemetostat Time Frame: Up to 72 months	CL/F will be used to generate estimates of tazemetostat AUC	Up to 72 months
Population PK parameters of first-order absorption rate constant (Ka) for tazemetostat. Time Frame: Up to 72 months		Up to 72 months
Percentage of Participants Experiencing Adverse Events (AEs) Time Frame: Up to 72 months	An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 72 months
Percentage of Participants with Clinically Significant Changes in Physical Examination Time Frame: Up to 72 months	Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.	Up to 72 months
Percentage of Participants with Clinically Significant Changes in Vital Signs Time Frame: Up to 72 months	Percentage of participants with clinically significant changes in vital signs findings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.	Up to 72 months
Percentage of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Readings Time Frame: Up to 72 months	Percentage of participants with clinically significant changes in ECG Readings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.	Up to 72 months
Performance status evaluated by Eastern Cooperation Oncology Group (ECOG) Time Frame: Up to 72 months	ECOG is a 6-point performance status scale used to assess performance using PA as a key indicator (e.g., 0 = fully active, 2 = up and about more than 50% of walking hours, 5 = dead) Performance status will be assessed per usual clinical practice and will be recorded in the medical record.	Up to 72 months
Duration of Study Drug Exposure Time Frame: Up to 72 months	Duration of exposure to study drug will be reported.	Up to 72 months
Total Number of Treatment Cycles Time Frame: Up to 72 months	Total number of treatment cycles for the study drug will be reported.	Up to 72 months
Percentage of Study Drug Taken by Participants Time Frame: Up to 72 months		Up to 72 months
Average Dose Intensity of Study Drug Time Frame: Up to 72 months	The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).	Up to 72 months
Number of Participants Requiring Dose Reductions, Treatment Interruption or Treatment Discontinuation Time Frame: Up to 72 months		Up to 72 months
Population PK parameters of oral volume of distribution (Vd/F) of tazemetostat. Time Frame: Up to 72 months		Up to 72 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Epizyme, Inc.

Investigators

Study Director: Ipsen Medical Director, Ipsen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 11, 2020

Primary Completion (Estimated)

September 30, 2029

Study Completion (Estimated)

April 27, 2032

Study Registration Dates

First Submitted

December 12, 2019

First Submitted That Met QC Criteria

January 8, 2020

First Posted (Actual)

January 13, 2020

Study Record Updates

Last Update Posted (Actual)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 18, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

EZH-302
2019-003333-42 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

IPD Sharing Time Frame

Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.

IPD Sharing Access Criteria

Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Follicular Lymphoma

Joseph Tuscano
National Cancer Institute (NCI); Genentech, Inc.; Pharmacyclics LLC.

Recruiting

Obinutuzumab, Ibrutinib, and Venetoclax for the Treatment of Previously Untreated Stage II-IV Follicular Lymphoma

Ann Arbor Stage II Follicular Lymphoma | Ann Arbor Stage III Follicular Lymphoma | Ann Arbor Stage IV Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular Lymphoma

United States
National Cancer Institute (NCI)

Recruiting

Obinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular Lymphoma

United States
Memorial Sloan Kettering Cancer Center
Fox Chase Cancer Center; Pharmacyclics LLC.

Terminated

Ibrutinib for Patients With Follicular Lymphoma Without Complete Response to Initial Chemoimmunotherapy

Follicular Lymphoma | Follicular Lymphoma, Grade 1 | Follicular Lymphoma, Grade 2 | Follicular Lymphoma Grade IIIa

United States
National Cancer Institute (NCI)

Terminated

Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

Stage III Grade 1 Follicular Lymphoma | Stage III Grade 2 Follicular Lymphoma | Stage III Grade 3 Follicular Lymphoma | Stage IV Grade 1 Follicular Lymphoma | Stage IV Grade 2 Follicular Lymphoma | Stage IV Grade 3 Follicular Lymphoma

United States
Olivia Newton-John Cancer Research Institute
Bristol-Myers Squibb; Barwon Health; Austin Health; Eastern Health; Fiona Stanley... and other collaborators

Recruiting

Treatment Of Newly-diagnosed Follicular Lymphoma With CELMoD BMS-986369, Rituximab +/- Nivolumab. (TOP-FLOR)

Follicular Lymphoma Stage II | Follicular Lymphoma Stage III | Follicular Lymphoma Stage IV

Australia
Robert Lowsky
National Cancer Institute (NCI); Janssen, LP; The Leukemia and Lymphoma Society; Rising Tide Foundation

Completed

TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma

Mantle Cell Lymphoma | Marginal Zone Lymphoma | Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular Lymphoma

United States
Massachusetts General Hospital
TG Therapeutics

Active, not recruiting

Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma

Lymphoma | Follicular Lymphoma | Marginal Zone Lymphoma | Follicular Lymphoma, Grade 1 | Follicular Lymphoma Grade IIIa | Marginal Zone B Cell Lymphoma | Follicular Lymphoma Grade 2

United States
Fondazione Italiana Linfomi ONLUS

Completed

"MIRO" Molecularly Oriented Immuno-radio-therapy (FIL_MIRO)

Follicular Lymphoma, Grade 1 | Follicular Lymphoma, Grade 2 | Follicular Lymphoma Grade 3A

Italy
National Cancer Institute (NCI)
Celgene Corporation

Active, not recruiting

Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma

Ann Arbor Stage III Grade 1 Follicular Lymphoma | Ann Arbor Stage III Grade 2 Follicular Lymphoma | Ann Arbor Stage IV Grade 1 Follicular Lymphoma | Ann Arbor Stage IV Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma | Ann Arbor Stage II Grade 3 Non-Contiguous... and other conditions

United States
M.D. Anderson Cancer Center
National Cancer Institute (NCI)

Active, not recruiting

Acalabrutinib, Lenalidomide, and Rituximab for the Treatment of CD20 Positive Stage III-IV, Grade 1-3a Follicular Lymphoma

Grade 3a Follicular Lymphoma | Ann Arbor Stage III Grade 1 Follicular Lymphoma | Ann Arbor Stage III Grade 2 Follicular Lymphoma | Ann Arbor Stage IV Grade 1 Follicular Lymphoma | Ann Arbor Stage IV Grade 2 Follicular Lymphoma | Ann Arbor Stage III Grade 3 Follicular Lymphoma | Ann Arbor Stage...

United States

Clinical Trials on Rituximab

Children's Oncology Group
National Cancer Institute (NCI)

Active, not recruiting

Rituximab and LMP-Specific T-Cells in Treating Pediatric Solid Organ Recipients With EBV-Positive, CD20-Positive Post-Transplant Lymphoproliferative Disorder

EBV-Related Post-Transplant Lymphoproliferative Disorder | Monomorphic Post-Transplant Lymphoproliferative Disorder | Polymorphic Post-Transplant Lymphoproliferative Disorder | Recurrent Monomorphic Post-Transplant Lymphoproliferative Disorder | Recurrent Polymorphic Post-Transplant Lymphoproliferative... and other conditions

United States
Academic and Community Cancer Research United
National Cancer Institute (NCI)

Active, not recruiting

Polatuzumab Vedotin, Venetoclax, and Rituximab and Hyaluronidase Human for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Grade 3a Follicular... and other conditions

United States
M.D. Anderson Cancer Center
National Cancer Institute (NCI)

Recruiting

Radiation Therapy and Rituximab in Treating Patients With Stage I-II Grade 1 or Grade 2 Follicular Lymphoma

Ann Arbor Stage I Grade 1 Follicular Lymphoma | Ann Arbor Stage I Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 1 Follicular Lymphoma | Ann Arbor Stage II Grade 2 Follicular Lymphoma

United States
National Cancer Institute (NCI)

Completed

Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

Ann Arbor Stage III Grade 1 Follicular Lymphoma | Ann Arbor Stage III Grade 2 Follicular Lymphoma | Ann Arbor Stage IV Grade 1 Follicular Lymphoma | Ann Arbor Stage IV Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma | Ann Arbor Stage II Grade 3 Non-Contiguous... and other conditions

United States
M.D. Anderson Cancer Center
National Cancer Institute (NCI)

Active, not recruiting

Ibrutinib With or Without Rituximab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia

Recurrent Small Lymphocytic Lymphoma | Prolymphocytic Leukemia | Recurrent Chronic Lymphocytic Leukemia

United States
Pfizer

Completed

Rheumatoid Arthritis Extension Trial For Subjects Who Have Participated In Other PF-05280586 Trials (REFLECTIONS B328-04)

Rheumatoid Arthritis

United States, Australia, Canada, Israel, Mexico, Colombia, Germany, Russian Federation, South Africa, United Kingdom
Mabion SA
Parexel

Withdrawn

MabionCD20® Compared to MabThera® and Rituxan® in Patients With Rheumatoid Arthritis (MABRIDGE)

Rheumatoid Arthritis
National Cancer Institute (NCI)

Active, not recruiting

Alisertib, Bortezomib, and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or B-cell Low Grade Non-Hodgkin Lymphoma

Recurrent Mantle Cell Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell Lymphoma

United States
National Cancer Institute (NCI)
Celgene Corporation

Active, not recruiting

Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma

Ann Arbor Stage III Grade 1 Follicular Lymphoma | Ann Arbor Stage III Grade 2 Follicular Lymphoma | Ann Arbor Stage IV Grade 1 Follicular Lymphoma | Ann Arbor Stage IV Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma | Ann Arbor Stage II Grade 3 Non-Contiguous... and other conditions

United States
M.D. Anderson Cancer Center
National Cancer Institute (NCI)

Recruiting

Zanubrutinib and Rituximab for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

United States

Study of Tazemetostat Versus Placebo When Given in Combination With Lenalidomide and Rituximab in Participants With Relapsed/Refractory Follicular Lymphoma (SYMPHONY-1)

Symphony-1: 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

Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Estimated)

Phase

Contacts and Locations

Study Contact

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Investigators

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Estimated)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Actual)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

IPD Plan Description

IPD Sharing Time Frame

IPD Sharing Access Criteria

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

Clinical Trials on Follicular Lymphoma

Clinical Trials on Rituximab

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Gabon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations