AzTrials
AzTrials

Relapsed/Refractory Follicular LymphomaPhase 3SYMPHONY-1NCT04224493

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.

A Phase 3 study testing Tazemetostat, Lenalidomide and Rituximab in people with Relapsed/Refractory Follicular Lymphoma and Follicular Lymphoma, run by Epizyme, Inc. at 204 sites in 17 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tazemetostat, Lenalidomide and Rituximab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
599 participants
Where
204 sitesin 17 countries
Study dates
11 Jun 2020to 1 Mar 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • Systemic therapy includes treatments such as:
  • Rituximab monotherapy
  • Chemotherapy given with or without rituximab
  • Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab.
  • Systemic therapy does not include, for example:
  • Local involved field radiotherapy for limited-stage disease
  • Helicobacter pylori eradication
  • Prior investigational therapies will be allowed provided the subject has received at least 1 prior systemic therapy as discussed in Inclusion Criterion #6a.
  • Prior autologous/allogeneic hematopoietic stem cell transplant (HSCT) will be allowed.
  • 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
  • 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:
  • 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.
  • Platelets ≥75,000/mm3 (≥75 × 10^9/L)
  • Evaluated at least 7 days after last platelet transfusion.
  • 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.
  • 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.

Who cannot join

  • 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).
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  • 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.
  • 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.
  • 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.

Trial locations and contacts

204 sites in 17 countries.

204 sites in 17 countries

United States57 sites

  • New Mexico Cancer Care Alliance

    Albuquerque, New Mexico, 87131-0001

  • Texas Oncology - Amarillo

    Amarillo, Texas, 79124

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Messino Cancer Center

    Asheville, North Carolina, 28806

  • Texas Oncology-Austin Midtown

    Austin, Texas, 78705

  • Rocky Mountain Cancer Centers (RMCC) - Boulder

    Boulder, Colorado, 80303

  • Gabrail Cancer Center Research

    Canton, Ohio, 44718

  • TOI - Clinical Research

    Cerritos, California, 90703

  • University of Chicago

    Chicago, Illinois, 60637

  • Oncology Hematology Care (OHC), Inc. - Kenwood Office

    Cincinnati, Ohio, 45236

  • UCSF Fresno

    Clovis, California, 93611

  • Levine Cancer Institute - Concord

    Concord, North Carolina, 28205

  • Texas Oncology - Medical City Dallas Pediatric Hematology

    Dallas, Texas, 75230

  • Texas Oncology-Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • Astera Cancer Care

    East Brunswick, New Jersey, 08816

  • Astera Cancer Center

    East Brunswick, New Jersey, 08816

  • Willamette Valley Cancer Institute and Research Center - Oncology

    Eugene, Oregon, 97401

  • Cancer Specialists of North Florida

    Fleming Island, Florida, 32003

  • Florida Cancer Specialists & Research Institute (FCS) - Fort Myers Cancer Center

    Fort Myers, Florida, 33908

  • Regional Cancer Care Associates-Freehold

    Freehold, New Jersey, 07728

  • Virginia Cancer Specialists

    Gainesville, Virginia, 22155

  • St. Mary's Hospital and Regional Medical Center - St. Mary's

    Grand Junction, Colorado, 81501

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Millennium Physicians - Oncology

    Houston, Texas, 77090

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • UC San Diego Health Sciences

    La Jolla, California, 92093

  • Regional Cancer Care Associates LLC - Little Silver

    Little Silver, New Jersey, 07739

  • Southern Cancer Center

    Mobile, Alabama, 36608

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Weill Cornell Medicine-New York Presbyterian Hospital

    New York, New York, 10021

  • Columbia U - Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Illinois Cancer Specialists

    Niles, Illinois, 60714

  • Hematology Oncology Associates of Rockland, P.C.

    Nyack, New York, 10960

  • Florida Cancer Affiliates/Ocala Oncology - Clinic

    Ocala, Florida, 34474

  • University Of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • FirstHealth of the Carolinas

    Pinehurst, North Carolina, 28374

  • Western Pennsylvania Hospital Hematology & Cellular Therapy

    Pittsburgh, Pennsylvania, 15524

  • Texas Oncology

    Plano, Texas, 75075

  • BRCR Medical Center, INC

    Plantation, Florida, 33322

  • Oncology and Hematology Associates of Southwest Virginia Inc.

    Roanoke, Virginia, 24014

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55901

  • Utah Cancer Specialists/ IHO Corp

    Salt Lake City, Utah, 84106

  • Huntsman Cancer Institute; The University of Utah

    Salt Lake City, Utah, 84112

  • Mays Cancer Center

    San Antonio, Texas, 78229

  • UCLA Clinical Research Unit Hematology/Oncology

    Santa Monica, California, 90404

  • Florida Cancer Specialists

    St. Petersburg, Florida, 33705

  • Florida Cancer Specialists - Panhandle

    Tallahassee, Florida, 32308

  • H Lee Moffitt Cancer Center and Research Institute I

    Tampa, Florida, 33612

  • Arizona Oncology Associates - Tuscon-Rusadill Road

    Tucson, Arizona, 85704

  • UT Health East Texas HOPE Cancer Center - Tyler

    Tyler, Texas, 75701

  • USO Texas Oncology - Tyler

    Tyler, Texas, 75702

  • Texas Oncology- Weslaco

    Weslaco, Texas, 78596

  • Florida Cancer Specialists & Research Institute (FCS) - Atlantis

    West Palm Beach, Florida, 33401

  • Wheeling Hospital

    Wheeling, West Virginia, 26003

  • Regional Medical Oncology Center

    Wilson, North Carolina, 27895

  • St. Joseph Mercy Hospital

    Ypsilanti, Michigan, 48197

Other trials in United States

France23 sites

  • Centre Hospitalier Universitaire D'Angers - Hématologie Clinique

    Angers

  • CHRU de Besançon- Hopital Jean Minjoz

    Besançon, 25000

  • Institut Bergonie

    Bordeaux, Gironde, 33000

  • CHRU Brest Hôp Morvan

    Brest, Brittany Region, 29609

  • CHU de Clermont-Ferrand, site Estaing

    Clermont-Ferrand, 63000

  • Hopital Henri Mondor - Hemopathies Lymphoides

    Créteil, Île-de-France Region, 94010

  • CHU de Grenoble - Hopital Albe

    La Tronche, Isere, 38700

  • Centre Hospitalier Le Mans

    Le Mans, Sarthe, 72000

  • Centre Hospitalier Docteur Schaffner

    Lens

  • CHRU de Lille Hop Claude Huriez

    Lille, Nord, 59037

  • CHU de Limoges Dupuytren

    Limoges, Haute-Vienne, 87042

  • Centre Hosp Mulh Hop Emile Muller

    Mulhouse, Haut-Rhin, 68100

  • CHU de Nantes - Hematologie

    Nantes, Loire-Atlantique, 44000

  • L'Hôpital Privé Confluent

    Nantes, 44202

  • L'hôpital Privé du Concluent

    Nantes

  • Hopital Saint Louis

    Paris, 75010

  • Centre Hospitalier - Hôpital de jour d'Hématologie

    Périgueux

  • Centre Hospitalier Universitaire de Bordeaux-Hopital du Haut Leveque

    Pessac, Aquitaine, 33600

  • Centre Hospitalier Universitaire de Poitiers

    Poitiers

  • Centre Henri Becquerel

    Rouen, Haute-Normandie, 76038

  • CHU de Nancy Brabois

    Vandœuvre-lès-Nancy, 54511

  • Centre Hospitalier Bretagne Atlantique

    Vannes, 56017

  • Institut Gustave Roussy

    Villejuif

Other trials in France

China20 sites

  • Peking University Third Hospital

    Beijing, 100191

  • The First Bethune Hospital of Jilin University

    Changchun, Jinlin, 130021

  • Hunan Cancer Hospital

    Changsha, Hunan, 410013

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian, 350001

  • The Affiliated Hospital of Guizhou Medical University

    Guiyang, Guizhou, 550004

  • The First Affiliated Hospital Zhejiang University School of Medicine

    Hangzhou

  • Tongji Hospital of Tongji Medical College of HUST

    Hangzhou

  • Jiangxi Cancer Hospital

    Nanchang

  • The Affiliated Hospital of Qingdao University

    Qingdao, Shandong, 266071

  • Shandong Cancer Hospital

    Shandong

  • Ruijin Hospital, Shanghai Jiaotong University School of Medicine

    Shanghai, Shanghai Municipality, 20025

  • Tongji Hospital of Tongji University

    Shanghai

  • The Fourth Hospital of Hebei Medical University

    Shijiazhuang, Hebei, 050011

  • Sichuan Provincial People's Hospital

    Sichuan

  • Shanxi Bethune Hospital

    Taiyuan, Shanxi, 30032

  • Tianjin Medical University Cancer Institute & Hospital

    Tianjin, 300060

  • The First Affiliated Hospital of Xiamen University

    Xiamen, Fujian, 361003

  • The Second Affiliated Hospital Zhejiang University School of Medicine

    Zhejiang, Hangzhou, 310000

  • Henan Provincial People's Hospital

    Zhengzhou, Henan, 450008

  • Henan Cancer Hospital

    Zhengzhou, Henan, 45008

Other trials in China

Italy19 sites

  • ASST Spedali Civili di Brescia

    Brescia, 25123

  • PO Garibaldi-Nesima, ARNAS Garibaldi

    Catania, 95122

  • AOU Careggi

    Florence, 50134

  • Ospedale Vito Fazzi, ASL Lecce

    Lecce

  • Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori IRCCS

    Meldola, Forli-Cesena, 47014

  • IEO - Istituto Europeo di Oncologia, IRCCS

    Milan

  • Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda

    Milan

  • Ospedale Niguarda, ASST Grande Ospedale Metropolitano Niguarda

    Milan

  • Ospedale San Gerardo, ASST di Monza

    Monza

  • AOU Federico II

    Naples, Campania, 80122

  • Ospedale Civile S.Spirito, PO di Pescara, AUSL Pescara

    Pescara

  • Ospedale Infermi di Rimini, AUSL Rimini, Distretto di Rimini, Presidio di Rimini, Santarcangelo di Romagna e Novafeltria

    Rimini

  • Catholic University Of Sacred Heart

    Roma, 00168

  • PU Campus Bio-Medico di Roma

    Roma

  • Regina Elena, Istituto Nazionale dei Tumori , IFO, IRCCS

    Roma

  • Azienda Ospedaliera Santa Maria di Terni

    Terni, 05100

  • Azienda Ospedaliera Ordine Mauriziano di Torino, Ospedale Umberto I di Torino

    Torino

  • Ospedale S.Giacomo Apostolo, PO Castelfranco Veneto, AULSS 2 Marca Trevigiana

    Treviso

  • Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), Ospedale Maggiore

    Trieste

Other trials in Italy

Brazil14 sites

  • Hospital Haroldo Juacaba - Instituto do Cancer do Ceara

    Ceará

  • Hospital Santa Cruz

    Curitiba

  • HC-UFG - Hospital das CLINICAS da Universidade Federal de Go

    Goiânia

  • Association Hospital de Caridade de Iju

    Ijuí

  • Liga Norte Riograndense Contra o Cancer

    Natal

  • Hospital de Clinicas de Porto Alegre - Centro de Pesquisa Clinica

    Porto Alegre

  • Instituto D'Or de Pesquisa e Ensino- Recife

    Recife

  • Instituto de Psiquiatria - UFRJ

    Rio de Janeiro

  • Instituto Nacional de Câncer - INCA

    Rio de Janeiro

  • Fundacao Antonio Prudente - Hospital A.C.Camargo Cancer Center

    São Paulo

  • Hospital Alemao Oswaldo Cruz (HAOC)

    São Paulo

  • Instituto D'or de Pesquisa e Ensino

    São Paulo

  • Instituto de Oncologia e Hematologia - HEMOMED

    São Paulo

  • Irmandade Santa Casa de Misericordia de Sao Paulo

    São Paulo

Other trials in Brazil

Spain11 sites

  • Hospital Universitari Vall d'Hebrón

    Barcelona, Cataluny, 08035

  • Hospital Del Mar

    Barcelona, 08003

  • Hospital Virgen de la Arrixaca

    El Palmar

  • Hospital Univ. Infanta Leonor

    Madrid, 28031

  • Hospital Universitario La Paz

    Madrid, 28046

  • Clínica Universidad de Navarra

    Madrid

  • Hospital Costa del Sol

    Marbella, Málaga, 29603

  • C.H. de Navarra

    Pamplona

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario Nuestra Señora de Valme

    Seville, 41014

  • Hospital Universitario Virgen De La Macarena

    Seville

Other trials in Spain

Australia9 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • GenesisCare - St Andrew's

    Adelaide

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Monash Health

    Clayton, Victoria, 3168

  • Peninsula Health - Frankston

    Frankston

  • Barwon Health, University Hospital Geelong

    Geelong, Victoria, 3220

  • Royal Hobart Hospital

    Hobart

  • Hollywood Private Hospital

    Nedlands, Western Australia, 6009

  • Gold Coast University Hosptial

    Southport

Other trials in Australia

Germany8 sites

  • Vivantes Klinikum am Urban Hämatologie und Onkologie

    Berlin

  • Universitaetsklinikum Bonn AöR

    Bonn, North Rhine-Westphalia, 53127

  • Städt. Krankenhaus Kiel

    Kiel, Schleswig-Holstein, 24116

  • University Medical Center Schleswig Holstein

    Kiel

  • Universitätsmedizin Mainz

    Mainz, Hesse, 55131

  • Kliniken Maria Hilf GmbH

    Mönchengladbach, North Rhine-Westphalia, 41063

  • Klinikum Der Universität München AöR

    München, Bavaria, 81377

  • Diakoneo Diak Schwaebisch Hall gGmbH

    Schwäbisch Hall, Baden-Wurttemberg, 74523

Other trials in Germany

Poland7 sites

  • Pratia Onkologia Katowice

    Katowice

  • Pratia MCM Krakow

    Krakow, 30-727

  • Centrum Medyczne Pratia Poznan

    Skórzewo, Greater Poland Voivodeship, 60-185

  • MICS Centrum Medyczne Torun

    Torun, 87-100

  • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

    Warsaw, Masovian Voivodeship, 02-781

  • MTZ Clinical Research powered by Pratia

    Warsaw

  • Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu

    Wroclaw, 50-367

Other trials in Poland

South Korea7 sites

  • Pusan National University Hospital

    Busan

  • Gachon University Gil Medical Center

    Incheon

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], 06591

  • Severance Hospital, Yonsei University Health System

    Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, 03722

  • Samsung Medical Center

    Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, 06351

  • Seoul National University Hospital

    Seoul, Seoul Teugbyeolsi, 03080

  • Ajou University Hospital

    Suwon

Other trials in South Korea

United Kingdom7 sites

  • The Clatterbridge Cancer Centre NHS Foundation Trust - Clatterbridge Cancer Centre

    Bebington

  • Royal Cornwall Hospitals NHS Trust - Royal Cornwall Hospital

    Cornwell

  • Western General Hospital - Haematology

    Edinburgh, Edinburgh, City of, EH4 2XU

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • Imperial College Healthcare NHS Trust - Hammersmith Hospital

    London, London City, W12 0HS

  • St Bartholomew's Hospital Barts Health NHS Trust

    London, London, City of, EC1A 7BE

  • Northwick Park Hospital Middlesex, United Kindgom, HA1 3UJ

    Middlesex

Other trials in United Kingdom

Canada5 sites

  • Centre Hospitalier de l'Universite de Montreal (CHUM)

    Montreal, Quebec, H2X 3E4

  • Sir Mortimer B Davis/Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Nova Scotia Health Centre for Clinical Research

    Nova Scotia

  • Sunnybrook Health Sciences Centre Odette Cancer Centre

    Ottawa

  • University Health Network Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Taiwan5 sites

  • Buddihist Tzu Chi Medical Foundation- Hualien Tzu Chi Hospital

    Hualien City

  • Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology

    Kaohsiung City, 833

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Cheng Kung University Hospital

    Tainan, 704

  • National Taiwan University Hospital

    Taipei

Other trials in Taiwan

Turkey (Türkiye)5 sites

  • Ankara University Medical Faculty - Hematology

    Ankara

  • Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research

    Ankara

  • Gazi University Medical Faculty

    Ankara

  • Medipol Bagcilar Mega Hospital

    Istanbul

  • Ondokuz Mayis University Medical Faculty - Hematology

    Samsun

Other trials in Turkey (Türkiye)

Hungary3 sites

  • Semmelweis Egyetem Általános Orvostudományi Kar

    Budapest, 1088

  • Országos Onkológiai Intézet

    Budapest, 1122

  • Debreceni Egyetem Klinikai Központ

    Debrecen, Hajdú-Bihar, 4032

Other trials in Hungary

Belgium2 sites

  • Universitair Ziekenhuis Gent

    Ghent, Oost-Vlaanderen, 9000

  • UZ Leuven - Campus Gasthuisberg

    Leuven, Vlaams Brabant, 3000

Other trials in Belgium

Singapore2 sites

  • National Cancer Center Singapore

    Singapore

  • Tan Tock Seng Hospital

    Singapore

Other trials in Singapore

About this study

Official title: 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.

Read more

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.

Read the 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

Being tested
Tazemetostat, Placebo oral tablet, Lenalidomide, Rituximab
Keywords
Epizyme, Tazverik, Tazemetostat (EPZ-6438), Lenalidomide, Revlimid, Rituximab, Rituxan, Follicular lymphoma, EZH2
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TazemetostatDrug

    Also called EPZ-6438, IPN60200

    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.

  • TazemetostatDrug

    Also called EPZ-6438, IPN60200

    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.

  • Placebo oral tabletDrug

    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.

  • LenalidomideCombination product

    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.

  • RituximabCombination product

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

Study groups in NCT04224493
Study groupRoleWhat they receive
Tazemetostat + R2 armExperimentalStage 1 (Phase 1b): completed * Tazemetostat escalated 400mg PO twice daily to 600mg PO twice daily (BD) to 800mg PO BD in 28-day cycles * Rituximab 375mg/m2 IV on days 1, 8, 15, \& 22 of cycle 1; then on day 1 of cycles 2-5 * Lenalidomide 20mg or 10mg, administered PO QD on days 1-21 for 12 cycles Stage 2: * Tazemetostat 800mg administered PO BD in continuous 28-day cycles. * Rituximab 375mg/m2 IV on days 1, 8, 15, \& 22 of cycle 1; then on day 1 of cycles 2-5 * Lenalidomide 20mg or 10mg, administered PO QD on days 1-21 for 12 cycles 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
Receives: Drug: Tazemetostat; Combination Product: Lenalidomide; Combination Product: Rituximab
Placebo + R2 ArmPlacebo comparatorParticipants 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: * 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 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.
Receives: Drug: Placebo oral tablet; Combination Product: Lenalidomide; Combination Product: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b: Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2)

    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).

    Measured: Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 was selected at the end of Stage 1

  2. Phase 3: Progression-Free Survival (PFS) in the Intent-to-treat wild-type (ITT-WT) populations

    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.

    Measured: Stage 2: Up to 72 months

  3. Phase 3: PFS in the Intent-to-treat mutant-type (ITT-MT) population

    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.

    Measured: Stage 2: Up to 72 months

  4. Phase 3: PFS in the R/R FL population regardless of mutation status by Investigator assessment

    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.

    Measured: Stage 2: Up to 72 months

  5. Phase 3: Progression-Free Survival (PFS) in the all comer (ITT-All) populations.

    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.

    Measured: Stage 2: Up to 72 months

Secondary outcomes (30)

  1. Phase 1b: Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax).

    Cmax will be recorded from the PK blood samples collected.

    Measured: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)

  2. Phase 1b: PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax)

    Measured: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)

  3. 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)],

    Measured: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)

  4. Phase 1b: PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-∞)]

    Measured: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)

  5. Phase 1b: The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit

    Measured: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)

  6. Phase 3: Complete Response Rate (CRR) in ITT-WT population

    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.

    Measured: Stage 2: Up to 96 months

  7. Phase 3: CRR in ITT-MT population

    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.

    Measured: Stage 2: Up to 96 months

  8. Phase 3: CRR in the Relapsed/Refractory (R/R) Follicular Lymphoma (FL) population regardless of mutation status

    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.

    Measured: Stage 2: Up to 96 months

  9. Phase 3: Objective Response Rate (ORR) in the ITT-WT population

    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.

    Measured: Stage 2: Up to 96 months

  10. Phase 3: ORR in the ITT-MT population

    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.

    Measured: Stage 2: Up to 96 months

  11. Phase 3: ORR in the R/R FL population regardless of mutation status

    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.

    Measured: Stage 2: Up to 96 months

  12. Phase 3: Overall Survival (OS) in the ITT-WT population

    OS is defined as the time from the date of randomization until death due to any cause.

    Measured: Stage 2: Up to 96 months

  13. Phase 3: OS in the ITT-MT population

    Measured: Stage 2: Up to 96 months

  14. Phase 3: OS in the R/R FL population regardless of mutation status

    Measured: Stage 2: Up to 96 months

  15. Phase 3: PFS in the ITT-WT population, assessed by a blinded IRC

    Measured: Stage 2: Up to 96 months

  16. Phase 3: PFS in the ITT-MT population, assessed by a blinded IRC

    Measured: Stage 2: Up to 96 months

  17. Phase 3: PFS in the R/R FL population regardless of mutation status, assessed by a blinded IRC

    Measured: Stage 2: Up to 96 months

  18. Phase 3: Duration Of Response (DOR) in the ITT-WT population

    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.

    Measured: Stage 2: Up to 96 months

  19. Phase 3: DOR in the ITT-MT population

    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.

    Measured: Stage 2: Up to 96 months

  20. Phase 3: DOR in the R/R FL population regardless of mutation status

    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.

    Measured: Stage 2: Up to 96 months

  21. Phase 3: Disease Control Rate (DCR) in the ITT-WT population

    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.

    Measured: Stage 2: Up to 96 months

  22. Phase 3: DCR in the ITT-MT population

    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.

    Measured: Stage 2: Up to 96 months

  23. Phase 3: DCR in the R/R FL population regardless of mutation status

    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.

    Measured: Stage 2: Up to 96 months

  24. PK parameters will be summarized by plasma concentrations of tazemetostat and lenalidomide descriptively.

    PK assessments will be conducted on samples collected until the urgent safety measure. No further PK analyses are performed post-urgent safety measure.

    Measured: Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)

  25. Percentage of Participants Experiencing Adverse Events (AEs)

    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.

    Measured: Up to 36 months

  26. Percentage of Participants with Clinically Significant Changes in Physical Examination

    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.

    Measured: Up to 36 months

  27. Percentage of Participants with Clinically Significant Changes in Vital Signs

    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.

    Measured: Up to 36 months

  28. Percentage of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Readings

    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.

    Measured: Up to 72 months

  29. Performance status evaluated by Eastern Cooperation Oncology Group (ECOG)

    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.

    Measured: Up to 72 months

  30. Duration of Study Drug Exposure

    Study drug exposure reflects administration prior to implementation of the urgent safety measure. No further investigational drug exposure occurs post-urgent safety measure.

    Measured: Up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2020
  2. Study start11 Jun 2020
  3. Primary completion13 Feb 2027 (estimated)
  4. Study completion1 Mar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Stage 1: Open-Label (Phase 1b: Safety run-in): All participants received Tazemetostat in combination with Lenalidomide and Rituximab Stage 2: Double-blinded (Phase 3): * Study drug arm: Tazemetostat in combination with Lenalidomide and Rituximab * Placebo arm: Placebo in combination with Lenalidomide and Rituximab Stage 3: Long-term Follow-up of participants in Stage 1/2 after treatment with tazemetostat for long-term safety monitoring
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
599 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04224493
Sponsor's protocol ID
EZH-302
Other IDs
2019-003333-42, 2024-510690-16-00, 2019
Acronym
SYMPHONY-1
Status last verified
Sep 2026
First submitted
12 Dec 2019
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Cao J, Chen G, Qiu L, Zhang L, Jiang M, Cheng Y, Zhang Q, Liu L, Li P, Shuang Y, Wang H, Xue H, Wu H, Zheng M, Zhou K, Li Z, Jing H, Yang W, Zhu Z, Li W, Wangwu J, Huang H, Jia Q, Chen D, Fan S, Shi MM, Su W. Efficacy and safety of tazemetostat, an EZH2 inhibitor, in Chinese patients with relapsed/refractory follicular lymphoma: a multicentre, single-arm, phase 2 study. EClinicalMedicine. 2025 Aug 18;87:103399. doi: 10.1016/j.eclinm.2025.103399. eCollection 2025 Sep.

    PubMed 40896460

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tazemetostat, Lenalidomide and Rituximab in people with Relapsed/Refractory Follicular Lymphoma and Follicular Lymphoma, run by Epizyme, Inc. at 204 sites in 17 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 60 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 204 sites in United States, France, China, Italy, Brazil and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04224493, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.

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