A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age 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
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 a period of improvement after that follows a treatment regimen and 'refractory' when treatment no longer works.
Stage 1 of this trial studied 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 1 of the study is completed.
Stages 2 and 3 were designed to 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. However, following an urgent safety measure, treatment with tazemetostat and placebo was discontinued, enrollment was stopped, and the study was unblinded. As a result, post-urgent safety measure analyses are descriptive in nature.
Study Overview
Status
Conditions
Detailed Description
In Stage 2, participants were enrolled into study cohorts based on whether they have a specific genetic mutation in the EZH2 gene. All participants received treatment in 28-day cycles. After 12 cycles, they continued with maintenance treatment using either the study drug or placebo, depending on their original treatment group. However, following the urgent safety measure, treatment was permanently discontinued and no further interventional procedures are being conducted.
The study included participants with and without the mutation in EZH2 gene. Enrollment was to be completed separately for each group. In China, some participants also had extra blood tests to better understand how the drug behaves in the body; no further pharmacokinetic data are being collected following the urgent safety measure.
Stage 3 focuses on long-term safety monitoring after the urgent safety measure. Participants treated with tazemetostat will be followed for up to 5 years after the last dose of tazemetostat
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Adelaide, Australia
- GenesisCare - St Andrew's
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Frankston, Australia
- Peninsula Health - Frankston
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Hobart, Australia
- Royal Hobart Hospital
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Southport, Australia
- Gold Coast University Hosptial
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South Australia
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Adelaide, South Australia, Australia, 5000
- Royal Adelaide Hospital
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Bedford Park, South Australia, Australia, 5042
- Flinders Medical Centre
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Victoria
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Clayton, Victoria, Australia, 3168
- Monash Health
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Geelong, Victoria, Australia, 3220
- Barwon Health, University Hospital Geelong
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Hollywood Private Hospital
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Oost-Vlaanderen
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Ghent, Oost-Vlaanderen, Belgium, 9000
- Universitair Ziekenhuis Gent
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Vlaams Brabant
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Leuven, Vlaams Brabant, Belgium, 3000
- UZ Leuven - Campus Gasthuisberg
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Ceará, Brazil
- Hospital Haroldo Juacaba - Instituto do Cancer do Ceara
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Curitiba, Brazil
- Hospital Santa Cruz
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Goiânia, Brazil
- HC-UFG - Hospital das CLINICAS da Universidade Federal de Go
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Ijuí, Brazil
- Association Hospital de Caridade de Iju
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Natal, Brazil
- Liga Norte Riograndense Contra o Câncer
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Porto Alegre, Brazil
- Hospital de Clinicas de Porto Alegre - Centro de Pesquisa Clinica
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Recife, Brazil
- Instituto D'Or de Pesquisa e Ensino- Recife
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Rio de Janeiro, Brazil
- Instituto Nacional de Cancer - INCa
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Rio de Janeiro, Brazil
- Instituto de Psiquiatria - UFRJ
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São Paulo, Brazil
- Instituto D'Or de Pesquisa e Ensino
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São Paulo, Brazil
- Fundacao Antonio Prudente - Hospital A.C.Camargo Cancer Center
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São Paulo, Brazil
- Hospital Alemao Oswaldo Cruz (HAOC)
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São Paulo, Brazil
- Instituto de Oncologia e Hematologia - HEMOMED
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São Paulo, Brazil
- Irmandade Santa Casa de Misericordia de Sao Paulo
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Nova Scotia, Canada
- Nova Scotia Health Centre for Clinical Research
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Ottawa, Canada
- Sunnybrook Health Sciences Centre Odette Cancer Centre
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- University Health Network Princess Margaret Hospital
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Quebec
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Montreal, Quebec, Canada, H2X 3E4
- Centre Hospitalier de l'Université de Montréal (CHUM)
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Montreal, Quebec, Canada, H3T 1E2
- Sir Mortimer B Davis/Jewish General Hospital
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Beijing, China, 100191
- Peking University Third Hospital
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Hangzhou, China
- The First Affiliated Hospital Zhejiang University School of Medicine
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Hangzhou, China
- Tongji Hospital of Tongji Medical College of HUST
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Nanchang, China
- Jiangxi Cancer Hospital
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Shandong, China
- Shandong Cancer Hospital
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Shanghai, China
- Tongji Hospital of Tongji University
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Sichuan, China
- Sichuan Provincial People's Hospital
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Tianjin, China, 300060
- Tianjin Medical University Cancer Institute & Hospital
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Fujian
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Fuzhou, Fujian, China, 350001
- Fujian Medical University Union Hospital
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Xiamen, Fujian, China, 361003
- The First Affiliated Hospital of Xiamen University
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Guizhou
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Guiyang, Guizhou, China, 550004
- The Affiliated Hospital of Guizhou Medical University
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Hangzhou
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Zhejiang, Hangzhou, China, 310000
- The Second Affiliated Hospital Zhejiang University School of Medicine
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Hebei
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Shijiazhuang, Hebei, China, 050011
- The Fourth Hospital of Hebei Medical University
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Henan
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Zhengzhou, Henan, China, 45008
- Henan Cancer Hospital
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Zhengzhou, Henan, China, 450008
- Henan Provincial People's Hospital
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Hunan
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Changsha, Hunan, China, 410013
- Hunan Cancer Hospital
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Jinlin
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Changchun, Jinlin, China, 130021
- The First Bethune Hospital of Jilin University
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Shandong
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Qingdao, Shandong, China, 266071
- The Affiliated Hospital of Qingdao University
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Shanghai Municipality
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Shanghai, Shanghai Municipality, China, 20025
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
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Shanxi
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Taiyuan, Shanxi, China, 30032
- Shanxi Bethune Hospital
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Angers, France
- Centre Hospitalier Universitaire D'Angers - Hématologie Clinique
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Besançon, France, 25000
- CHRU de Besançon- Hopital Jean Minjoz
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Clermont-Ferrand, France, 63000
- CHU de Clermont-Ferrand, site Estaing
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Lens, France
- Centre Hospitalier Docteur Schaffner
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Nantes, France, 44202
- L'Hôpital Privé Confluent
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Nantes, France
- L'hôpital Privé du Concluent
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Poitiers, France
- Centre Hospitalier Universitaire de Poitiers
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Périgueux, France
- Centre Hospitalier - Hôpital de jour d'Hématologie
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Vandœuvre-lès-Nancy, France, 54511
- CHU de Nancy Brabois
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Vannes, France, 56017
- Centre Hospitalier Bretagne Atlantique
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Villejuif, France
- Institut Gustave Roussy
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Aquitaine
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Pessac, Aquitaine, France, 33600
- Centre Hospitalier Universitaire de Bordeaux-Hopital du Haut Leveque
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Brittany Region
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Brest, Brittany Region, France, 29609
- CHRU Brest Hôp Morvan
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Gironde
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Bordeaux, Gironde, France, 33000
- Institut Bergonie
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Haut-Rhin
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Mulhouse, Haut-Rhin, France, 68100
- Centre Hosp Mulh Hop Emile Muller
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Haute-Normandie
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Rouen, Haute-Normandie, France, 76038
- Centre Henri Becquerel
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Haute-Vienne
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Limoges, Haute-Vienne, France, 87042
- CHU de Limoges Dupuytren
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Isere
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La Tronche, Isere, France, 38700
- CHU de Grenoble - Hopital Albe
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Loire-Atlantique
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Nantes, Loire-Atlantique, France, 44000
- CHU de Nantes - Hematologie
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Nord
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Lille, Nord, France, 59037
- CHRU de Lille Hop Claude Huriez
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Paris
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Paris, Paris, France, 75010
- Hopital Saint Louis
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Sarthe
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Le Mans, Sarthe, France, 72000
- Centre Hospitalier Le Mans
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Île-de-France Region
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Créteil, Île-de-France Region, France, 94010
- Hopital Henri Mondor - Hemopathies Lymphoides
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Berlin, Germany
- Vivantes Klinikum am Urban Hämatologie und Onkologie
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Kiel, Germany
- University Medical Center Schleswig Holstein
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Baden-Wurttemberg
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Schwäbisch Hall, Baden-Wurttemberg, Germany, 74523
- Diakoneo Diak Schwaebisch Hall gGmbH
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Bavaria
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München, Bavaria, Germany, 81377
- Klinikum der Universität München AÖR
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Hesse
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Mainz, Hesse, Germany, 55131
- Universitätsmedizin Mainz
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North Rhine-Westphalia
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Bonn, North Rhine-Westphalia, Germany, 53127
- Universitaetsklinikum Bonn AöR
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Mönchengladbach, North Rhine-Westphalia, Germany, 41063
- Kliniken Maria Hilf GmbH
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Schleswig-Holstein
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Kiel, Schleswig-Holstein, Germany, 24116
- Städt. Krankenhaus Kiel
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Budapest
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Budapest, Budapest, Hungary, 1088
- Semmelweis Egyetem Általános Orvostudományi Kar
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Budapest, Budapest, Hungary, 1122
- Orszagos Onkologiai Intezet
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Hajdú-Bihar
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Debrecen, Hajdú-Bihar, Hungary, 4032
- Debreceni Egyetem Klinikai Kozpont
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Brescia, Italy, 25123
- ASST Spedali Civili di Brescia
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Catania, Italy, 95122
- PO Garibaldi-Nesima, ARNAS Garibaldi
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Lecce, Italy
- Ospedale Vito Fazzi, Asl Lecce
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Milan, Italy
- Ospedale Niguarda, ASST Grande Ospedale Metropolitano Niguarda
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Milan, Italy
- IEO - Istituto Europeo di Oncologia, IRCCS
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Milan, Italy
- Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
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Monza, Italy
- Ospedale San Gerardo, ASST di Monza
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Pescara, Italy
- Ospedale Civile S.Spirito, PO di Pescara, AUSL Pescara
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Rimini, Italy
- Ospedale Infermi di Rimini, AUSL Rimini, Distretto di Rimini, Presidio di Rimini, Santarcangelo di Romagna e Novafeltria
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Roma, Italy, 00168
- Catholic University Of Sacred Heart
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Roma, Italy
- PU Campus Bio-Medico di Roma
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Roma, Italy
- Regina Elena, Istituto Nazionale dei Tumori , IFO, IRCCS
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Torino, Italy
- Azienda Ospedaliera Ordine Mauriziano di Torino, Ospedale Umberto I di Torino
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Treviso, Italy
- Ospedale S.Giacomo Apostolo, PO Castelfranco Veneto, AULSS 2 Marca Trevigiana
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Trieste, Italy
- Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), Ospedale Maggiore
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Campania
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Naples, Campania, Italy, 80122
- AOU Federico II
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Firenze
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Florence, Firenze, Italy, 50134
- AOU Careggi
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Forli-Cesena
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Meldola, Forli-Cesena, Italy, 47014
- Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori IRCCS
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Terni
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Terni, Terni, Italy, 05100
- Azienda Ospedaliera Santa Maria di Terni
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Katowice, Poland
- Pratia Onkologia Katowice
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Krakow, Poland, 30-727
- Pratia McM Krakow
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Torun, Poland, 87-100
- MICS Centrum Medyczne Torun
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Warsaw, Poland
- MTZ Clinical Research Powered by Pratia
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Wroclaw, Poland, 50-367
- Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu
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Greater Poland Voivodeship
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Skórzewo, Greater Poland Voivodeship, Poland, 60-185
- Centrum Medyczne Pratia Poznan
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Masovian Voivodeship
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Warsaw, Masovian Voivodeship, Poland, 02-781
- Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
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Singapore, Singapore
- Tan Tock Seng Hospital
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Singapore, Singapore
- National Cancer Center Singapore
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Busan, South Korea
- Pusan National University Hospital
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Incheon, South Korea
- Gachon University Gil Medical Center
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Suwon, South Korea
- Ajou University Hospital
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Seoul Teugbyeolsi
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Seoul, Seoul Teugbyeolsi, South Korea, 03080
- Seoul National University Hospital
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Seoul Teugbyeolsi [Seoul-T'Ukp
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Seoul, Seoul Teugbyeolsi [Seoul-T'Ukp, South Korea, 03722
- Severance Hospital, Yonsei University Health System
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Seoul, Seoul Teugbyeolsi [Seoul-T'Ukp, South Korea, 06351
- Samsung Medical Center
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Seoul Teugbyeolsi [Seoul-T'Ukp]
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Seoul, Seoul Teugbyeolsi [Seoul-T'Ukp], South Korea, 06591
- The Catholic University of Korea, Seoul St. Mary's Hospital
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El Palmar, Spain
- Hospital Virgen de la Arrixaca
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Madrid, Spain
- Clinica Universidad de Navarra
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Pamplona, Spain
- C.H. de Navarra
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Salamanca, Spain, 37007
- Hospital Universitario de Salamanca
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Seville, Spain
- Hospital Universitario Virgen de la Macarena
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Barcelona
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Barcelona, Barcelona, Spain, 08003
- Hospital del Mar
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Cataluny
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Barcelona, Cataluny, Spain, 08035
- Hospital Universitari Vall d'Hebron
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Madrid
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Madrid, Madrid, Spain, 28046
- Hospital Universitario La Paz
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Madrid, Madrid, Spain, 28031
- Hospital Univ. Infanta Leonor
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Málaga
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Marbella, Málaga, Spain, 29603
- Hospital Costa del Sol
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Sevilla
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Seville, Sevilla, Spain, 41014
- Hospital Universitario Nuestra Senora De Valme
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Hualien City, Taiwan
- Buddihist Tzu Chi Medical Foundation- Hualien Tzu Chi Hospital
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Kaohsiung City, Taiwan, 833
- Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
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Taichung, Taiwan, 40705
- Taichung Veterans General Hospital
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Taipei, Taiwan
- National Taiwan University Hospital
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Tainan
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Tainan, Tainan, Taiwan, 704
- National Cheng Kung University Hospital
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Ankara, Turkey (Türkiye)
- Gazi University Medical Faculty
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Ankara, Turkey (Türkiye)
- Ankara University Medical Faculty - Hematology
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Ankara, Turkey (Türkiye)
- Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research
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Istanbul, Turkey (Türkiye)
- Medipol Bagcilar Mega Hospital
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Samsun, Turkey (Türkiye)
- Ondokuz Mayis University Medical Faculty - Hematology
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Bebington, United Kingdom
- The Clatterbridge Cancer Centre NHS Foundation Trust - Clatterbridge Cancer Centre
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Cornwell, United Kingdom
- Royal Cornwall Hospitals NHS Trust - Royal Cornwall Hospital
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Glasgow, United Kingdom, G12 0YN
- Beatson West of Scotland Cancer Centre
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Middlesex, United Kingdom
- Northwick Park Hospital Middlesex, United Kindgom, HA1 3UJ
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Edinburgh, City of
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Edinburgh, Edinburgh, City of, United Kingdom, EH4 2XU
- Western General Hospital - Haematology
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London City
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London, London City, United Kingdom, W12 0HS
- Imperial College Healthcare NHS Trust - Hammersmith Hospital
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London, City of
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London, London, City of, United Kingdom, EC1A 7BE
- St Bartholomew's Hospital Barts Health NHS Trust
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Alabama
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Mobile, Alabama, United States, 36608
- Southern Cancer Center
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Arizona
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Tucson, Arizona, United States, 85704
- Arizona Oncology Associates - Tuscon-Rusadill Road
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California
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Cerritos, California, United States, 90703
- TOI - Clinical Research
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Clovis, California, United States, 93611
- UCSF Fresno
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La Jolla, California, United States, 92093
- UC San Diego Health Sciences
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Santa Monica, California, United States, 90404
- UCLA Clinical Research Unit Hematology/Oncology
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Colorado
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Boulder, Colorado, United States, 80303
- Rocky Mountain Cancer Centers (RMCC) - Boulder
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Grand Junction, Colorado, United States, 81501
- St. Mary's Hospital and Regional Medical Center - St. Mary's
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Florida
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Fleming Island, Florida, United States, 32003
- Cancer Specialists of North Florida
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Fort Myers, Florida, United States, 33908
- Florida Cancer Specialists & Research Institute (FCS) - Fort Myers Cancer Center
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Jacksonville, Florida, United States, 32224
- Mayo Clinic
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Ocala, Florida, United States, 34474
- Florida Cancer Affiliates/Ocala Oncology - Clinic
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Plantation, Florida, United States, 33322
- Brcr Medical Center, Inc
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St. Petersburg, Florida, United States, 33705
- Florida Cancer Specialists
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Tallahassee, Florida, United States, 32308
- Florida Cancer Specialists - Panhandle
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Tampa, Florida, United States, 33612
- H Lee Moffitt Cancer Center and Research Institute I
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West Palm Beach, Florida, United States, 33401
- Florida Cancer Specialists & Research Institute (FCS) - Atlantis
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago
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Niles, Illinois, United States, 60714
- Illinois Cancer Specialists
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Comprehensive Cancer Center
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Ypsilanti, Michigan, United States, 48197
- St. Joseph Mercy Hospital
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Minnesota
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Rochester, Minnesota, United States, 55901
- Mayo Clinic - Rochester
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Nebraska
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Omaha, Nebraska, United States, 68198
- University Of Nebraska Medical Center
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New Jersey
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East Brunswick, New Jersey, United States, 08816
- Astera Cancer Care
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East Brunswick, New Jersey, United States, 08816
- Astera Cancer Center
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Freehold, New Jersey, United States, 07728
- Regional Cancer Care Associates-Freehold
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Little Silver, New Jersey, United States, 07739
- Regional Cancer Care Associates LLC - Little Silver
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New Mexico
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Albuquerque, New Mexico, United States, 87131-0001
- New Mexico Cancer Care Alliance
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New York
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New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
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New York, New York, United States, 10021
- Weill Cornell Medicine-New York Presbyterian Hospital
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New York, New York, United States, 10032
- Columbia U - Herbert Irving Comprehensive Cancer Center
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Nyack, New York, United States, 10960
- Hematology Oncology Associates of Rockland, P.C.
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North Carolina
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Asheville, North Carolina, United States, 28806
- Messino Cancer Center
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Concord, North Carolina, United States, 28205
- Levine Cancer Institute - Concord
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Pinehurst, North Carolina, United States, 28374
- FirstHealth of the Carolinas
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Wilson, North Carolina, United States, 27895
- Regional Medical Oncology Center
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Ohio
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Canton, Ohio, United States, 44718
- Gabrail Cancer Center Research
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Cincinnati, Ohio, United States, 45236
- Oncology Hematology Care (OHC), Inc. - Kenwood Office
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Oregon
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Eugene, Oregon, United States, 97401
- Willamette Valley Cancer Institute and Research Center - Oncology
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15524
- Western Pennsylvania Hospital Hematology & Cellular Therapy
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Tennessee
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Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute
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Texas
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Amarillo, Texas, United States, 79124
- Texas Oncology - Amarillo
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Austin, Texas, United States, 78705
- Texas Oncology-Austin Midtown
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Dallas, Texas, United States, 75246
- Texas Oncology-Baylor Charles A. Sammons Cancer Center
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Dallas, Texas, United States, 75230
- Texas Oncology - Medical City Dallas Pediatric Hematology
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Houston, Texas, United States, 77030
- The University of Texas MD Anderson Cancer Center
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Houston, Texas, United States, 77090
- Millennium Physicians - Oncology
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Plano, Texas, United States, 75075
- Texas Oncology
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San Antonio, Texas, United States, 78229
- Mays Cancer Center
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Tyler, Texas, United States, 75702
- USO Texas Oncology - Tyler
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Tyler, Texas, United States, 75701
- UT Health East Texas HOPE Cancer Center - Tyler
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Weslaco, Texas, United States, 78596
- Texas Oncology- Weslaco
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Utah
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Salt Lake City, Utah, United States, 84106
- Utah Cancer Specialists/ IHO Corp
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Salt Lake City, Utah, United States, 84112
- Huntsman Cancer Institute; The University of Utah
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Virginia
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Gainesville, Virginia, United States, 22155
- Virginia Cancer Specialists
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Roanoke, Virginia, United States, 24014
- Oncology and Hematology Associates of Southwest Virginia Inc.
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West Virginia
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Wheeling, West Virginia, United States, 26003
- Wheeling Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
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, or per country adult legal age regulations, 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: Participants 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. Participants seropositive for HBV with undetectable HBV DNA by PCR are permitted with appropriate antiviral prophylaxis.
- Negative test results for hepatitis C virus (HCV) Note: Participants 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. Based on Cancer Clinical Trial Eligibility Criteria: Patients with HIV, Hepatitis B Virus, or Hepatitis C Virus Infections - Guidance for Industry (https://www.fda.gov/media/121319/download), patients with HIV should be considered eligible if they have CD4+ T-cell counts ≥ 350 cells/uL and in general, if they have not had an opportunistic infection within the past 12 months. Other exclusion criteria should be considered regarding the drug-drug interaction if antiviral drugs are used. Therefore, in case of controlled HIV infection, since antiviral drugs are used, trial patients should be on established ART for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrolment.
- 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:
- Cytotoxic chemotherapy - At least 21 days.
- Noncytotoxic chemotherapy (eg, small molecule inhibitor) - At least 14 days.
- Nitrosoureas - At least 6 weeks.
- Monoclonal and/or bispecific antibodies or CAR T - At least 28 days.
- 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:
- Total bilirubin ≤1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
- 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) 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 day 14 (for FCBP with irregular menstrual cycles) and day 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 are surgically sterilized (ie, total hysterectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose of study treatment.
- 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.
- 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: Participants 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 participant'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
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Tazemetostat + R2 arm
Stage 1 (Phase 1b): completed
Stage 2:
Maintenance Therapy (Stages 1&2): Tazemetostat 800mg PO BD dose for up to 2 years after the initial 12 months of combination therapy. Following an Independent Data Monitoring Committee review, an urgent safety measure was implemented and administration of tazemetostat was permanently discontinued. No further investigational treatment is administered. Participants previously exposed to tazemetostat enter protocol-specified long-term safety follow-up |
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 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.
Stage 2: 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:
Stage 1 (Phase 1b): Tazemetostat was 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. Following implementation of the urgent safety measure, tazemetostat administration was discontinued. No further dosing is performed.
Other Names:
|
|
Placebo Comparator: Placebo + R2 Arm
Participants were assigned to receive placebo in combination with lenalidomide and rituximab. Following implementation of the urgent safety measure, placebo administration was permanently discontinued. No further investigational treatment is administered. Stage 2:
Maintenance Therapy (Stage 2): 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. |
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 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.
Stage 2: 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. Following implementation of the urgent safety measure, placebo administration was discontinued. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Phase 1b: 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 was selected at the end of Stage 1
|
The safety and tolerability of tazemetostat in combination with R2 in subjects with R/R FL were evaluated.
RP3D of tazemetostat for further evaluation in phase 3 was 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 was selected at the end of Stage 1
|
|
Phase 3: Progression-Free Survival (PFS) in the Intent-to-treat wild-type (ITT-WT) populations
Time Frame: Stage 2: 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. PFS will be assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further efficacy data are collected, and any post-urgent safety measure analyses are descriptive in nature. |
Stage 2: Up to 72 months
|
|
Phase 3: PFS in the Intent-to-treat mutant-type (ITT-MT) population
Time Frame: Stage 2: 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.
|
Stage 2: Up to 72 months
|
|
Phase 3: PFS in the R/R FL population regardless of mutation status by Investigator assessment
Time Frame: Stage 2: Up to 72 months
|
PFS is defined as the time from the date of randomization to the first observation of documented objective disease progression per the 2014 Lugano Classification or death due to any cause, whichever occurs first. 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. |
Stage 2: Up to 72 months
|
|
Phase 3: Progression-Free Survival (PFS) in the all comer (ITT-All) populations.
Time Frame: Stage 2: 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. PFS will be assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further efficacy data are collected, and any post-urgent safety measure analyses are descriptive in nature. |
Stage 2: Up to 72 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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
|
|
Percentage of Participants Experiencing Adverse Events (AEs)
Time Frame: Up to 36 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 36 months
|
|
Percentage of Participants with Clinically Significant Changes in Physical Examination
Time Frame: Up to 36 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 36 months
|
|
Percentage of Participants with Clinically Significant Changes in Vital Signs
Time Frame: Up to 36 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 36 months
|
|
Phase 1b: Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax).
Time Frame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
Cmax will be recorded from the PK blood samples collected.
|
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
|
Phase 1b: PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax)
Time Frame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
|
|
Phase 1b: 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: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
|
|
Phase 1b: PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-∞)]
Time Frame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
|
|
Phase 1b: The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit
Time Frame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
|
|
|
Phase 3: Complete Response Rate (CRR) in ITT-WT population
Time Frame: Stage 2: Up to 96 months
|
CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded Independent Review Committee (IRC). CRR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: CRR in ITT-MT population
Time Frame: Stage 2: Up to 96 months
|
CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC. CRR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: CRR in the Relapsed/Refractory (R/R) Follicular Lymphoma (FL) population regardless of mutation status
Time Frame: Stage 2: Up to 96 months
|
CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC. CRR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: Objective Response Rate (ORR) in the ITT-WT population
Time Frame: Stage 2: Up to 96 months
|
ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC. ORR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: ORR in the ITT-MT population
Time Frame: Stage 2: Up to 96 months
|
ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC. ORR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: ORR in the R/R FL population regardless of mutation status
Time Frame: Stage 2: Up to 96 months
|
ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC. ORR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: Overall Survival (OS) in the ITT-WT population
Time Frame: Stage 2: Up to 96 months
|
OS is defined as the time from the date of randomization until death due to any cause.
|
Stage 2: Up to 96 months
|
|
Phase 3: OS in the ITT-MT population
Time Frame: Stage 2: Up to 96 months
|
Stage 2: Up to 96 months
|
|
|
Phase 3: OS in the R/R FL population regardless of mutation status
Time Frame: Stage 2: Up to 96 months
|
Stage 2: Up to 96 months
|
|
|
Phase 3: PFS in the ITT-WT population, assessed by a blinded IRC
Time Frame: Stage 2: Up to 96 months
|
Stage 2: Up to 96 months
|
|
|
Phase 3: PFS in the ITT-MT population, assessed by a blinded IRC
Time Frame: Stage 2: Up to 96 months
|
Stage 2: Up to 96 months
|
|
|
Phase 3: PFS in the R/R FL population regardless of mutation status, assessed by a blinded IRC
Time Frame: Stage 2: Up to 96 months
|
Stage 2: Up to 96 months
|
|
|
Phase 3: Duration Of Response (DOR) in the ITT-WT population
Time Frame: Stage 2: Up to 96 months
|
DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whichever occurs first, for those participants with a CR or PR, as assessed by the Investigator and by a blinded IRC. DOR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: DOR in the ITT-MT population
Time Frame: Stage 2: Up to 96 months
|
DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whichever occurs first, for those participants with a CR or PR, as assessed by the Investigator and by a blinded IRC. DOR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: DOR in the R/R FL population regardless of mutation status
Time Frame: Stage 2: Up to 96 months
|
DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whichever occurs first, for those participants with a CR or PR, as assessed by the Investigator and by a blinded IRC. DOR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: Disease Control Rate (DCR) in the ITT-WT population
Time Frame: Stage 2: Up to 96 months
|
DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC. DCR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: DCR in the ITT-MT population
Time Frame: Stage 2: Up to 96 months
|
DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC. DCR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
Phase 3: DCR in the R/R FL population regardless of mutation status
Time Frame: Stage 2: Up to 96 months
|
DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC. DCR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
Stage 2: Up to 96 months
|
|
PK parameters will be summarized by plasma concentrations of tazemetostat and lenalidomide descriptively.
Time Frame: Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
|
PK assessments will be conducted on samples collected until the urgent safety measure.
No further PK analyses are performed post-urgent safety measure.
|
Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
|
|
Duration of Study Drug Exposure
Time Frame: Up to 36 months
|
Study drug exposure reflects administration prior to implementation of the urgent safety measure.
No further investigational drug exposure occurs post-urgent safety measure.
|
Up to 36 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Ipsen Medical Director, Ipsen
Publications and helpful links
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
- Neoplasms
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphatic Diseases
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Hemic and Lymphatic Diseases
- Lymphoma, Follicular
- Amino Acids, Peptides, and Proteins
- Proteins
- Organic Chemicals
- Heterocyclic Compounds, 1-Ring
- Heterocyclic Compounds
- Heterocyclic Compounds, 2-Ring
- Heterocyclic Compounds, Fused-Ring
- Carboxylic Acids
- Piperidines
- Antibodies, Monoclonal
- Antibodies
- Immunoglobulins
- Immunoproteins
- Blood Proteins
- Serum Globulins
- Globulins
- Antibodies, Monoclonal, Murine-Derived
- Phthalimides
- Phthalic Acids
- Acids, Carbocyclic
- Piperidones
- Isoindoles
- Lenalidomide
- Rituximab
- tazemetostat
Other Study ID Numbers
- EZH-302
- 2019-003333-42 (EudraCT Number)
- 2024-510690-16-00 (Ctis)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
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
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