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    The EU Clinical Trials Register currently displays   42174   clinical trials with a EudraCT protocol, of which   6938   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2019-003333-42
    Sponsor's Protocol Code Number:EZH-302
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-09-22
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2019-003333-42
    A.3Full title of the trial
    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
    Étude de phase 1b/3 randomisée, en double aveugle, en 3 étapes, avec design adaptatif selon biomarqueur, du tazémétostat ou placebo en association au lénalidomide et rituximab chez des patients atteints d’un lymphome folliculaire en rechute ou réfractaire
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of tazemetostat or placebo in combination with lenalidomide plus rituximab in subjects with relapsed/refractory follicular lymphoma
    Étude du tazémétostat ou placebo en association au lénalidomide et rituximab chez des patients atteints d’un lymphome folliculaire en rechute ou réfractaire
    A.4.1Sponsor's protocol code numberEZH-302
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04224493
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorEpizyme, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportEpizyme, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEpizyme, Inc
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street Address400 Technology Square, 4th Floor
    B.5.3.2Town/ cityCambridge, MA
    B.5.3.3Post code02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number001855500-1011
    B.5.6E-mailclinicaltrials@epizyme.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEMA/111729/2018
    D.3 Description of the IMP
    D.3.1Product nameTazemetostat
    D.3.2Product code EPZ-6438
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTAZEMETOSTAT
    D.3.9.1CAS number 1403254-99-8
    D.3.9.2Current sponsor codeEPZ-6438
    D.3.9.4EV Substance CodeSUB178719
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name MabThera®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMabThera®
    D.3.2Product code MabThera®
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name MabThera®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMabThera®
    D.3.2Product code MabThera®
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Revlimid
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRevlimid
    D.3.2Product code Revlimid
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Revlimid
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRevlimid
    D.3.2Product code Revlimid
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Revlimid
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRevlimid
    D.3.2Product code Revlimid
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 7
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Revlimid
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRevlimid
    D.3.2Product code Revlimid
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 8
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Revlimid
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRevlimid
    D.3.2Product code Revlimid
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Relapsed/refractory follicular lymphoma
    Lymphome folliculaire en rechute ou réfractaire
    E.1.1.1Medical condition in easily understood language
    Relapsed/refractory follicular lymphoma
    Lymphome folliculaire en rechute ou réfractaire
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10016903
    E.1.2Term Follicle centre lymphomas, follicular grade I, II, III
    E.1.2System Organ Class 100000004851
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Stage 1, Safety Run-In
    Evaluate the safety and tolerability of tazemetostat in combination with lenalidomide + rituximab (R2) in subjects with relapsed/refractory (R/R) follicular lymphoma (FL) and to select a recommended phase 3 dose (RP3D) of tazemetostat for further evaluation in phase 3.

    Stage 2
    Evaluate and compare progression-free survival (PFS), as assessed by Investigators, of tazemetostat + R2 versus placebo + R2 in subjects with R/R FL who have completed at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy.
    Stade 1, phase de pré-inclusion pour la sécurité d’emploi
    Évaluer la sécurité d'emploi et la tolérance du tazémétostat en association avec le lénalidomide + rituximab (R2) chez des patients atteints de lymphome folliculaire (LF) en rechute ou réfractaire (R/R) et déterminer la dose recommandée en phase 3 (DRP3) du tazémétostat pour l'évaluation en phase 3.

    Stade 2
    Évaluer et comparer la survie sans progression (SSP), évaluée par les investigateurs, du tazémétostat + R2 par rapport au placebo + R2 chez des sujets atteints de LF R/R ayant terminé au moins 1 chimiothérapie, immunothérapie ou chimio-immunothérapie systémique antérieure.
    E.2.2Secondary objectives of the trial
    Stage 1, Safety Run-In:
    Assess the clinical activity and pharmacokinetics of tazemetostat when administered concomitantly with R2 in subjects with R/R FL

    Stage 2
    - Evaluate and compare PFS by blinded independent review committee (IRC)
    - Evaluate and compare objective response rate (ORR)
    - Evaluate and compare the duration of response (DOR)
    - Evaluate and compare the duration of complete response (DOCR)
    - Evaluate and compare the disease control rate (DCR)
    - Evaluate and compare health-related quality of life as measured by the EuroQOL 5 Dimension 5-Level (EQ-5D-5L) instrument
    - Evaluate and compare the overall survival (OS)
    - Assess population pharmacokinetic (PK) parameters, including exposure-response of tazemetostat when administered in combination with R2
    - Evaluate and compare safety and tolerability
    Stade 1: phase de pré-inclusion pour la sécurité d’emploi:
    Évaluer l'activité clinique et la pharmacocinétique du tazémétostat lorsqu'il est administré simultanément au R2 chez les patients atteints de LF R/R

    Stade 2
    -Évaluer et comparer la SSP en aveugle, rôle d’un comité d’examen indépendant (CEI)
    -Évaluer et comparer le taux de réponse objective (TRO)
    -Évaluer et comparer la durée de réponse (DDR)
    -Évaluer et comparer la durée de réponse complète (DDRC)
    -Évaluer et comparer le taux de contrôle de la maladie (TCM)
    -Évaluer et comparer la qualité de vie liée à la santé mesurée par le biais de l'outil EuroQOL5-Dimension 5-Level (EQ-5D-5L)
    -Évaluer et comparer la survie globale (SG)
    -Évaluer les paramètres de pharmacocinétique (PK) de la population, y compris la réponse à l’exposition du tazémétostat lorsqu’il est administré en association avec R2
    -Évaluer et comparer la sécurité d’emploi et la tolérance.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.
    2. Males or females are ≥18 years of age at the time of providing voluntary written informed consent.
    3. Life expectancy ≥3 months before enrollment.
    4. Subjects with a history of hepatitis B or C are eligible on the condition that subjects have adequate liver function as defined by Inclusion Criterion #15 and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA.
    5. Have histologically confirmed FL, grades 1 to 3A.
    6. 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 Prior investigational therapies will be allowed provided the subject has received at least 1 prior systemic therapy as discussed in Inclusion Criteria #6a.
    7. 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).
    8. Have measurable disease as defined by the Lugano Classification.
    9.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 antibody(ies) - At least 28 days.
    - Radiotherapy -At least 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation.
    10. Adequate renal function defined as calculated creatinine clearance ≥40 mL/minute per the Cockcroft and Gault formula or local institutional standard formula.
    11. Adequate bone marrow function.
    12. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [β-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of β-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study treatment. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutively amenorrhoeic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
    13. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to randomization, during treatment cycles, and for 30 days after the final dose of study treatment, and have a male partner who uses a condom. Highly effective contraception includes:
    - Double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide.
    - Placement of an intrauterine device.
    - Established hormonal contraceptive methods: oral, injectable, or implant. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 12 months after study drug discontinuation.
    14. All study participants enrolled must be registered into the mandatory Revlimid REMS™ program and be willing and able to comply with the requirements of the Revlimid REMS™ program as appropriate for the country in which the drug is being used. Female subjects of childbearing potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS™ program. Female subjects exempt from this requirement are subjects who have been in natural menopause for at least 2 years OR have had both ovaries and/or uterus removed.
    15. Male subjects must have had either a successful vasectomy OR they and their female partner must meet the criteria above (ie, not of childbearing potential OR practicing highly effective contraception and use a condom throughout the study period and for 30 days after study drug discontinuation).
    1. Ont volontairement accepté de fournir un consentement éclairé écrit et ont manifesté leurs volonté et capacité de respecter tous les aspects du protocole.
    . Hommes ou femmes âgés de ≥ 18 ans au moment de fournir un consentement éclairé écrit volontaire.
    3. Espérance de vie ≥ 3 mois avant l’inclusion.
    4. Les sujets ayant des antécédents d’hépatite B ou C sont admissibles à condition que les sujets aient une fonction hépatique adéquate tel que défini par le critère d’inclusion n°15 et soient négatifs à l’antigène de surface de l’hépatite B et/ou présentent un ARN indétectable du virus de l’hépatite C (VHC).
    5. Avoir un LF confirmé par histologie, de grades 1 à 3A.
    6. Doivent avoir été précédemment traités par au moins 1 chimiothérapie, immunothérapie ou chimioimmunothérapie systémique antérieure :
    a. La thérapie systémique comprend les traitements tels que :
    i. Rituximab en monothérapie
    ii. Chimiothérapie administrée avec ou sans rituximab
    iii. Radioimmunoconjugués comme l’ibritumomab tiuxétan marqué par le [90Y] et le tositumomab marqué par le [131I].
    b. La thérapie systémique ne comprend pas, par exemple :
    i. Radiothérapie locale du champ atteint pour une maladie à un stade limité
    ii. Éradication d’Helicobacter pylori
    c. Des thérapies expérimentales antérieures seront autorisées à condition que le sujet ait suivi au moins 1 thérapie systémique antérieure, tel que mentionné dans le critère d’inclusion n° 6a.
    7. Doit être en rechute, réfractaire, ou présenter une PM après le traitement par thérapie systémique (le caractère réfractaire étant défini comme inférieur à une RP ou une progression de la maladie < 6 mois après la dernière dose).
    8. Être atteint d’une maladie mesurable, comme défini par la classification de Lugano (Cheson, 2014).
    9. Délai entre la thérapie anticancéreuse antérieure et la première dose de tazémétostat comme suit :
    -Chimiothérapie cytotoxique – Au moins 21 jours.
    -Chimiothérapie non cytotoxique (p. ex. inhibiteur à petites molécules) – Au moins 14 jours.
    -Nitrosourées – Au moins 6 semaines.
    -Anticorps monoclonal(aux) – Au moins 28 jours.
    -Radiothérapie – Au moins 6 semaines à partir de la précédente thérapie par radio-isotope ; au moins 12 semaines à partir de 50 % d’irradiation pelvienne ou corporelle totale.
    10. Fonction rénale adéquate, définie par une clairance de la créatinine calculée ≥ 40 ml/minute selon la formule de Cockcroft et Gault ou la formule standard locale de l’établissement.
    11. onction adéquate de la moelle osseuse.
    12. Les femmes ne doivent ni allaiter ni être enceintes à la sélection ou à la visite de référence (documentation par un test négatif de la sous-unité bêta de la gonadotrophine chorionique humaine [beta-human chorionic gonadotropin, β -hCG] avec une sensibilité minimale de 25 UI/l ou unités équivalentes de β -hCG). Une évaluation de référence distincte est nécessaire si un test de grossesse négatif à la sélection a été obtenu plus de 72 heures avant la première dose du traitement à l’étude. Toutes les femmes seront considérées être en âge de procréer, sauf si elles sont ménopausées (au moins 12 mois consécutifs d’aménorrhée, dans la tranche d’âge appropriée, et sans autre cause connue ou suspectée) ou ont été stérilisées chirurgicalement (c.-à-d. ligature bilatérale des trompes, hystérectomie totale ou ovariectomie bilatérale, toutes par chirurgie au moins 1 mois avant l’administration de la dose).
    13. Les femmes en âge de procréer ne doivent pas avoir eu de rapports sexuels non protégés dans les 30 jours précédant l’entrée dans l’étude et doivent accepter d’utiliser une méthode de contraception hautement efficace, depuis le dernier cycle menstruel précédant la randomisation, pendant les cycles de traitement, et pendant 12 mois après la dernière dose du traitement à l’étude, et avoir un partenaire masculin qui utilise un préservatif.
    Les moyens de contraception hautement efficaces incluent :
    • Méthodes de contraception par double barrière telle que préservatif plus diaphragme ou cape cervicale avec spermicide.
    • Pose d’un dispositif intra-utérin.
    • Utilisation de méthodes reconnues de contraception hormonale : voie orale, injectable, ou implant. Les femmes utilisant des contraceptifs hormonaux doivent avoir pris une dose stable du même produit contraceptif hormonal pendant au moins 4 semaines avant l’administration et doit continuer d’utiliser le même contraceptif pendant l’étude et pendant 12 mois après l’arrêt du médicament à l’étude.
    14. Tous les participants à l’étude inclus doivent être inscrits au programme Revlimid REMS™ obligatoire et être désireux et capables de se conformer aux exigences du Revlimid REMS™ applicables pour le pays dans lequel le médicament est utilisé.

    * voir suite dans le résumé du protocole en Français.
    E.4Principal exclusion criteria
    1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
    2. Prior exposure to lenalidomide for the treatment of FL.
    3. Subjects who have mixed or transformed histology.
    4. 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).
    5. Has a prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL).
    6. Subjects with uncontrolled leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
    7. Subjects taking medications that are known potent cytochrome P450 (CYP)3A4 inducers/inhibitors (including St. John's wort).
    8. Are unwilling to exclude Seville oranges, grapefruit juice, AND grapefruit from their diet.
    9. 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.
    10. 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.
    11. 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.
    12. Prolongation of corrected QT interval using Fridericia's formula (QTcF) to >480 msec at screening or history of long QT syndrome.
    13. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.
    a. whereas subjects greater than 3 months since deep vein thrombosis/pulmonary embolism are eligible but recommended to receive prophylaxis.
    14. Have an active infection requiring systemic therapy.
    15. Known hypersensitivity to any component of tazemetostat, lenalidomide, or rituximab.
    16. Inability to be treated with a Pneumocystis prophylaxis medication.
    17. Have an active infection with hepatitis B virus (as measured by positive hepatitis B surface antigen), HCV (as measured by positive hepatitis C antibody), human immunodeficiency virus, OR human T-cell lymphotropic virus 1.
    a. Exceptions: Subjects with a history of hepatitis B or C who have normal ALT AND are hepatitis B surface antigen negative and/or have undetectable HCV RNA.
    18. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.
    19. Female subjects who are pregnant or breastfeeding.
    20. Subjects who have undergone a solid organ transplant.
    21. Subjects with malignancies other than FL. a. Exception: Subjects with another malignancy who have been disease-free for 5 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
    1. Exposition antérieure au tazémétostat ou à un/d’autre(s) inhibiteur(s) d’EZH2.
    2. Exposition antérieure au lénalidomide pour le traitement du LF.
    3. Sujets qui présentent une histologie mixte ou avec des variations.
    4. Sont atteints d’une thrombopénie, neutropénie ou anémie de grade ≥ 3 (selon les critères CTCAE version 5.0) ou des antécédents de tumeurs malignes myéloïdes, y compris d’un syndrome myélodysplasique (SMD).
    5. Ont des antécédents de lymphome lymphoblastique des lymphocytes T (LLB-T)/leucémie lymphoblastique aiguë des lymphocytes T (LLA-T).
    6. Sujets présentant des métastases leptoméningées non contrôlées ou des métastases cérébrales ou des antécédents de métastases cérébrales déjà traitées auparavant.
    7. Sujets prenant des médicaments qui sont réputés être de puissants inducteurs/inhibiteurs du cytochrome P450 (CYP) 3A4 (y compris du millepertuis)
    8. Ne veulent pas exclure les oranges de Séville, le jus de pamplemousse ET le pamplemousse de leur régime alimentaire.
    9. Intervention chirurgicale majeure dans les 4 semaines précédant la première dose de médicament à l’étude.
    a. Remarque : Une intervention chirurgicale mineure (p. ex. biopsie mineure du site extracrânien, pose d’un cathéter veineux central, révision de shunt) est autorisée dans les 3 semaines précédant l’inclusion.
    10. Ne parviennent pas à prendre de médicament par voie orale OU présentent un syndrome de malabsorption ou tout autre problème gastro-intestinal non contrôlé (p. ex. nausées, diarrhée, vomissements) susceptible de nuire à la biodisponibilité du tazémétostat.
    11. Déficience cardiovasculaire significative : antécédents d’insuffisance cardiaque congestive de classe supérieure à la classe II selon la New York Heart Association (NYHA), d’hypertension artérielle non contrôlée, d’angor instable, d’infarctus du myocarde ou d’accident vasculaire cérébral dans les 6 mois précédant la première dose de médicament à l’étude ; ou arythmie ventriculaire cardiaque.
    12. Allongement de l’intervalle QT corrigé à l’aide de la formule de Fridericia (QTcF) > 480 ms à la sélection ou antécédents de syndrome du QT long.
    3. Thrombose veineuse ou embolie pulmonaire dans les 3 mois précédant le début du traitement par tazémétostat.
    a. Tandis que les sujets ayant subi une thrombose veineuse profonde/embolie pulmonaire il y a plus de 3 mois sont éligibles, mais pour lesquels une prophylaxie est recommandée.
    14. Présentent une infection active nécessitant une thérapie systémique.
    15. Hypersensibilité connue à tout composant du tazémétostat, du lénalidomide ou du rituximab.
    16. Incapacité à être traités par médicament prophylactique de Pneumocystis.
    17. Présentent une infection active par le virus de l’hépatite B (mesurée par positivité à l’antigène de surface de l’hépatite B), le VHC (mesurée par positivité aux anticorps de l’hépatite C), le virus de l’immunodéficience humaine OU le virus T-lymphotropique humain de type 1.
    a. Exceptions : Les sujets ayant des antécédents d’hépatite B ou C qui présentent un taux normal d’ALAT ET sont négatifs à l’antigène de surface de l’hépatite B et/ou présentent un taux d’ARN du VHC indétectable.
    18. Toute autre maladie majeure qui, de l’avis de l’investigateur, augmenterait de manière importante le risque associé à la participation du sujet dans cette étude OU interférerait avec sa capacité à recevoir le traitement à l’étude ou terminer l’étude.
    19. Sujets de sexe féminin qui envisagent une grossesse ou qui allaitent.
    20. Sujets qui ont subi une greffe d’organe solide.
    21. Sujets atteints de tumeurs malignes autres que le LF.
    a. Exception : Sujets avec une autre tumeur maligne qui n’ont pas été malades pendant 5 ans, ou les sujets ayant des antécédents de cancer de la peau non mélanomateux entièrement réséqué ou de carcinome in situ traité avec succès sont éligibles.
    E.5 End points
    E.5.1Primary end point(s)
    Stage 1: RP3D of tazemetostat in combination with R2.
    The safety and tolerability of tazemetostat in combination with R2 in subjects with R/R FL will be evaluated. RP3D of tazemetostat for further evaluation in phase 3 will be selected as assessed by the occurrence of treatment-emergent dose-limiting toxicities (DLTs) and adverse events (AEs).

    Stage 2: Progression-free Survival (PFS)
    Evaluate and compare progression-free survival (PFS), as assessed by Investigators, of tazemetostat + R2 versus placebo + R2 in subjects with R/R FL who have completed at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy
    Stade 1: DRP3 de tazémétostat en association avec R2.
    La sécurité d’emploi et la tolérance du tazémétostat en association avec R2 chez des sujets atteints de LF R/R seront évaluées. La DRP3 de tazémétostat pour une évaluation en phase 3 sera déterminée par l'évaluation de l'incidence des toxicités limitant la dose (TLD) et des évènements indésirables (AEs) émergeant du traitement.

    Stade 2: la survie sans progression (SSP)
    Évaluer et comparer la survie sans progression (SSP), évaluée par les investigateurs, du tazémétostat + R2 par rapport au placebo + R2 chez des sujets atteints de LF R/R ayant terminé au moins 1 chimiothérapie, immunothérapie ou chimio-immunothérapie systémique antérieure
    E.5.1.1Timepoint(s) of evaluation of this end point
    Stage 1: Each cohort minimum 3 subjects. Evaluated for DLTs during the first 28 day cycle. 2-3 subjects 1 of the 6 subjects in the cohort experiences a DLT, the next dose level/cohort will be assessed. The RP3D for Phase 3 will be selected at in cohort experience

    Stage 2: Time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, assessed up to 72 months.
    Stade 1: 3 patients minimum dans chaque cohorte. Évalués pour les TLD pendant les 28 premiers jours du cycle. 2-3 patients, 1 des 6 patients dans la cohorte expérimentant la TLD, la prochaine dose/le prochain niveau seront évalués. La DRP3 de la phase 3 sera déterminée selon l'expérience avec la cohorte.

    Stade 2: le temps écoulé entre la date de randomisation et la progression de la maladie d’après la classification de Lugano de 2014 ou le décès, selon la première éventualité, évalué jusqu'à 72 mois.
    E.5.2Secondary end point(s)
    1. Pharmacokinetics of tazemetostat Maximum Plasma Concentration Cmax.
    Assess the pharmacokinetics of tazemetostat when administered concomitantly with R2 in subjects with R/R FL.
    2. PFS
    Stage 2: Evaluate and compare PFS by blinded independent review committee (IRC)
    3. Objective Response Rate
    Stage 2: Evaluate and compare objective response rate (ORR)
    4. Stage 2: Duration of response
    Evaluate and compare the duration of response (DOR)
    5. Stage 2: Duration of complete response.
    Evaluate and compare the duration of complete response (DOCR)
    6. Disease control rate
    Stage 2: Evaluate and compare the disease control rate (DCR)
    7. Overall Survival
    Stage 2: Evaluate and compare the overall survival (OS)
    8. EuroQOL
    Stage 2: Evaluate and compare health-related quality of life as measured by the EuroQOL 5-Dimension 5-Level (EQ-5D-5L) instrument
    9. Number of participants with treatment-related adverse events
    Stage 2: Evaluate and compare safety and tolerability between tazemetostat + R2 vs Placebo + R2.
    1. Pharmacocinétique de la concentration plasmatique maximum (Cmax) du tazémétostat.
    Évaluer la pharmacocinétique du tazmétostat lorsqu'il est administré simultanément au R2 chez des patients atteints de FL R/R.
    2 SSP
    Stade 2: évaluer et comparer le SSP par un comité d’examen indépendant (CEI), en aveugle
    3. Taux de réponse objective
    Stade 2: Évaluer et comparer le taux de réponse objective (TRO)
    4. Stade 2: durée de réponse
    Évaluer et comparer la durée de réponse (DDR)
    5. stade 2: durée de réponse complète (DDRC)
    Évaluer et comparer la durée de réponse complète (DDRC)
    6. Contrôle de la maladie
    Stade 2: évaluer et comparer le taux de contrôle de la maladie (TCM)
    7. survie globale
    Stade 2: évaluer et comparer la survie globale (SG)
    8. EuroQOL
    Stade 2: évaluer et comparer la qualité de vie liée à la santé mesurée par le biais de l’outil EuroQOL5-Dimension 5-Level (EQ-5D-5L)
    9. Nombre de participants avec des événements indésirables émergeant du traitement
    Stade 2: évaluer et comparer la sécurité d’emploi et tolérance entre le tazémétostat+R2 vs Placebo+R2
    E.5.2.1Timepoint(s) of evaluation of this end point
    Stage 1, Safety Run-In: PK Cmax is evaluated on Cycles 1 & 2 , days 1 & 15. (Each cycles is 28 days), and annually thereafter as long as patient is on study drug

    Stage 2 from randomization to time of disease progression per the 2014 Lugano Classification or death, whichever occurs first, assessed up to 72 months
    Stade 1, phase de pré-inclusion pour la sécurité d’emploi : PK Cmax est évalué aux cycles 1 et 2, jour 1 et 15. (Chaque cycle contient 28 jours), et annuellement par la suite, aussi longtemps que le patient est traité avec le produit à l'étude

    Stade 2, de la randomisation jusqu'à la progression de la maladie d’après la classification de Lugano de 2014 ou le décès, selon la première éventualité, évalué jusqu'à 72 mois
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    evaluate the efficacy and safety of tazemetostat in combination with R2
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Tazmetostat is studied in combination with R2
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Lenalidomide plus rituximab
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned15
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA56
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Belgium
    Canada
    France
    Germany
    Hungary
    Italy
    Korea, Republic of
    Poland
    Spain
    Taiwan
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last subject last visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days11
    E.8.9.2In all countries concerned by the trial years4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 317
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 201
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 176
    F.4.2.2In the whole clinical trial 518
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Post-study anticancer therapy will not be provided as part of this study. The subject may receive subsequent anticancer therapy at the discretion of the treating physician. The subsequent anticancer therapy should be documented on the eCRF. The subject will continue to be monitored until disease progression.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-11-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-10-12
    P. End of Trial
    P.End of Trial StatusOngoing
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