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Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
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  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43614   clinical trials with a EudraCT protocol, of which   7207   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
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    Summary
    EudraCT Number:2011-002792-42
    Sponsor's Protocol Code Number:RV-FOL-GELARC-0683
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2013-10-24
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2011-002792-42
    A.3Full title of the trial
    A phase 3 open label randomized study to compare the efficacy and safety of rituximab plus lenalidomide (CC-5013) versus rituximab plus chemotherapy followed by rituximab in subjects with previously untreated follicular lymphoma.
    Estudio en fase 3, abierto, aleatorizado, para comparer la eficacia y seguridad de Rituximab más Lenalidomida (CC-5013) frente a Rituximab más quimioterapia, seguido de Rituximab en pacientes con Linfoma Folicular sin tratamiento previo
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to compare the efficacy and safety of rituximab plus lenalidomide versus standart therapy with rituximab plus chemotherapy in subjects with previously untreated follicular lymphoma.
    Estudio para comparar la eficacia y la seguridad de rituximab con lenalidomida frente a quimioterapia convencional con rituximab en pacientes que no han sido previamente tratados para el linfoma folicular
    A.3.2Name or abbreviated title of the trial where available
    Relevance
    A.4.1Sponsor's protocol code numberRV-FOL-GELARC-0683
    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 SponsorLYSARC
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCelgene International Sarl
    B.4.2CountrySwitzerland
    B.4.1Name of organisation providing supportLYSARC
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationVALESTA CONSULTING, S.L.
    B.5.2Functional name of contact pointPILAR DURÁ SANJUÁN
    B.5.3 Address:
    B.5.3.1Street AddressGRAN VIA DE LES CORTS CATALANES, 583- PLANTA 5ª
    B.5.3.2Town/ cityBARCELONA
    B.5.3.3Post code08011
    B.5.3.4CountrySpain
    B.5.4Telephone number+34625259851
    B.5.5Fax number+34933063499
    B.5.6E-mailpilar.dura@valesta.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 Yes
    D.2.1.1.1Trade name REVLIMID 5 mg
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe Limited
    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 nameLENALIDOMIDE
    D.3.2Product code CC-5013
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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 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 Yes
    D.2.1.1.1Trade name REVLIMID
    D.2.1.1.2Name of the Marketing Authorisation holderCELGENE EUROPE LIMITED
    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 namelenalidomide
    D.3.2Product code CC-5013
    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.3.9.2Current sponsor codeCC-5013
    D.3.9.3Other descriptive nameSUB25389
    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.IMP: 3
    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 Yes
    D.2.1.1.1Trade name MABTHERA
    D.2.1.1.2Name of the Marketing Authorisation holderROCHE REGISTRATION LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical 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 milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameCYCLOPHOSPHAMIDE
    D.3.4Pharmaceutical form Powder for solution for injection/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 INNCYCLOPHOSPHAMIDE
    D.3.9.1CAS number 50-18-0
    D.3.9.4EV Substance CodeSUB06859MIG
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameCYCLOPHOSPHAMIDE
    D.3.4Pharmaceutical form Powder for solution for injection/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 INNCYCLOPHOSPHAMIDE
    D.3.9.1CAS number 50-18-0
    D.3.9.4EV Substance CodeSUB06859MIG
    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: 6
    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 Yes
    D.2.1.1.1Trade name MABTHERA
    D.2.1.1.2Name of the Marketing Authorisation holderROCHE REGISTRATION LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical 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 milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameVINCRISTINE
    D.3.4Pharmaceutical form Solution for injection
    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 INNVINCRISTINE
    D.3.9.1CAS number 57-22-7
    D.3.9.4EV Substance CodeSUB00059MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameDOXORUBICIN
    D.3.4Pharmaceutical form Concentrate for solution for injection/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 INNDOXORUBICIN
    D.3.9.1CAS number 23214-92-8
    D.3.9.4EV Substance CodeSUB06391MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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: 9
    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.2.1.2Country which granted the Marketing AuthorisationSpain
    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 namePREDNISONE
    D.3.4Pharmaceutical form 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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.3Other descriptive namePREDNISONE
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number2,5 to 50
    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: 10
    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.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameBENDAMUSTINE
    D.3.4Pharmaceutical form Powder for 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 INNBENDAMUSTINE
    D.3.9.1CAS number 16506-27-7
    D.3.9.4EV Substance CodeSUB05707MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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: 11
    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 Yes
    D.2.1.1.1Trade name REVLIMID 10 mg
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe Limited
    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 nameLENALIDOMIDE
    D.3.2Product code CC-5013
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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: 12
    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 Yes
    D.2.1.1.1Trade name REVLIMID 2,5 mg
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe Limited
    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 nameLENALIDOMIDE
    D.3.2Product code CC-5013
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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: 13
    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 Yes
    D.2.1.1.1Trade name REVLIMID 15 mg
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe Limited
    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 nameLENALIDOMIDE
    D.3.2Product code CC-5013
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Stage II-IV follicular lymphoma grade 1-3a not previously treated
    Linfoma folicular en estadio II-IV, grado 1-3a no previamente tratado
    E.1.1.1Medical condition in easily understood language
    Follicular lymphoma in need of treatment
    Linfoma folicular que requiera tratamiento
    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 14.1
    E.1.2Level PT
    E.1.2Classification code 10016908
    E.1.2Term Follicle centre lymphoma, follicular grade I, II, III stage II
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10016910
    E.1.2Term Follicle centre lymphoma, follicular grade I, II, III stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10016909
    E.1.2Term Follicle centre lymphoma, follicular grade I, II, III stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to compare the efficacy of rituximab plus lenalidomide to rituximab plus chemotherapy followed by rituximab in patients with previously untreated follicular lymphoma. Efficacy determination will be based upon the co-primary endpoints of complete response (CR/CRu) rate at 120 weeks and PFS assessed by the IRC using the IWG (Cheson, 1999) criteria.
    El objetivo primario de este ensayo es comparar la eficacia de Rituximab asociado a Lenalidomida frente a Rituximab combinado con quimioterapia, seguido de Rituximab, en pacientes que no hayan recibido tratamiento previo para el linfoma folicular. La determinación de la eficacia se basará en las covariables primarias de la tasa de respuesta completa (RC/RCnc) a las 120 semanas y la SLP (Supervivencia libre de progresión) evaluada por el IRC (comité de revisión independiente) mediante los criterios de respuesta IWG (Cheson, 1999).
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are:
    o To compare the efficacy of rituximab plus lenalidomide versus rituximab plus chemotherapy followed by rituximab using other parameters of efficacy:
    o Event Free Survival (EFS), Time to Next Anti-Lymphoma Treatment (TTNLT), and Overall Survival (OS).
    To compare the safety of rituximab plus lenalidomide versus rituximab plus chemotherapy followed by rituximab
    o Comparar la eficacia del Rituximab con Lenalidomida versus Rituximab y quimioterapia, seguido de Rituximab, empleando otros parámetros de eficacia como: Supervivencia Libre de Eventos (SLE), Tiempo hasta el próximo Tratamiento contra el Linfoma (TTNLT), y Supervivencia Global (SG).
    o Comparar la seguridad de Rituximab y Lenalidomida versus Rituximab y quimioterapia seguida de Rituximab.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    The exploratory objectives of the study are:
    ? CR rate at 120 weeks and PFS by 2007 Revised Response Criteria for Malignant Lymphoma incorporating FDG-PET (Cheson, 2007)
    ? Time to Treatment Failure (TTF)
    ? Time to Next Chemotherapy Treatment (TTNCT)
    ? Histological transformation rate at first progression
    ? To explore the relationship between lenalidomide exposure and response (hematology, biomarkers, and other clinical outcomes as appropriate).
    ? To compare the effects of rituximab plus lenalidomide versus rituximab plus chemotherapy followed by rituximab on minimal residual disease using PCR detection of the t(14;18) translocation in peripheral blood or other MRD assays.
    ? To compare the effects of rituximab plus lenalidomide versus rituximab plus chemotherapy followed by rituximab on immune competence
    ? Evaluate Fc-gamma receptor polymorphisms in blood samples collected pre-treatment and correlate with clinical outcomes
    ? To investigate potential predictive biomarkers of clinical response or resistance to rituximab plus lenalidomide, including, but not limited to, gene expression, analysis of acquired chromosomal aberrations (translocations, gains, deletions, single nucleotide polymorphisms, mutations), microRNA and protein expression in archival diagnostic or fresh tumor samples
    ? Health related quality of life as measured by the EORTC QLQ-C30

    To examine utility during the active, maintenance, and follow-up phases using the EQ-5D for the purpose of collecting information on the treatment regimens to support cost-effectiveness analyses and modeling.
    EXISTE UN SUBESTUDIO QUE NO SE VA A REALIZAR EN ESPAÑA
    E.3Principal inclusion criteria
    -Histologically confirmed CD20+ follicular lymphoma grade 1, 2 or 3a
    -Have no prior systemic treatment for lymphoma.
    -Must be in need of treatment
    -Bi-dimensionally measurable disease with at least one mass lesion > 2 cm that was not previously irradiated.
    -Stage II, III or IV disease.
    -Must be ? 18 years and sign an informed consent.
    -Performance status ? 2 on the ECOG scale.
    -Adequate hematological function
    -Females of childbearing potential (FCBP) receiving lenalidomide must have two negative pregnancy tests . She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy.
    -Male patients receiving lenalidomide must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation
    -All patients receiving lenalidomide must have an understanding that the study drug could have a potential teratogenic risk.
    -For all patients receiving Rituximab Women must not breast feed and must use effective contraception must not be pregnant and agree not to become pregnant during participation in the trial and during the 6 months thereafter. Men must agree not to father a child during participation in the trial and during the 6 months thereafter.
    1. CD20 positivo confirmado histológicamente y linfoma folicular grados 1, 2 ó 3a

    2. No haber recibido tratamiento previo para el linfoma.

    3. Deben estar en necesidad de tratamiento, demostrado al menos por uno de los siguientes criterios:
    - Enfermedad voluminosa definida como:
    * nodal o extranodal (excepto en bazo) con una masa > 7cm en el mayor diámetro o,
    * afectación de al menos 3 sitios nodales o extranodales (cada uno con un diámetro >3 cm)
    - Presencia de al menos uno de los siguientes síntomas B:
    * fiebre (>38ºC) de etiología poco clara
    * sudores nocturnos
    * pérdida de peso superior al 10% en los 6 meses previos
    - Esplenomegalia sintomática
    - Síndrome de compresión (uretral, orbital, gastrointestinal)
    - Cualquiera de las siguientes citopenias debidas a linfoma:
    * hemoglobina < 10g/dL (6.25 mmol/L)
    * plaquetas <100 x 109/L , o
    * recuento absoluto de neutrófilos (ANC) < 1.5 x 109/L
    - Derrame pleural o peritoneal seroso (independientemente del contenido celular)
    - LDH > ULN ó ?2 microglobulina > ULN

    4. Enfermedad bidimensional medible con al menos una lesión > 2 cm que no haya sido previamente irradiada.

    5. Estadio de la enfermedad II, III o IV.

    6. El paciente debe ser ? 18 años de edad y haber firmado el consentimiento informado.

    7. Performance status ? 2 en la escala ECOG.

    8. Función hematológica adecuada (excepto si las anormalidades están relacionadas con infiltración del linfoma en médula ósea) durante los 28 días previos a la firma del consentimiento informado, incluyendo:
    - Recuento absoluto de neutrófilos (ANC) ? 1.5 x 109/L
    - Recuento de plaquetas ? 75 x 109/L
    - Hemoglobina ? 8.0 g/dl (5 mmol/L)

    9. Capacidad de cumplimiento con las visitas y otros requisitos del protocolo.

    10. Las mujeres en edad fértil (FCBP)? que estén recibiendo Lenalidomida deben:
    Contar con 2 tests de embarazo negativos, verificados por el médico del estudio, previos al inicio de la terapia de estudio. Además deberá estar de acuerdo en realizarse más tests de embarazo durante el trascurso del ensayo y tras haber finalizado el tratamiento de estudio. Ello será aplicable aún cuando la paciente practique una abstinencia heterosexual completa.
    Aunque se comprometa a una completa abstinencia sexual (la cual será revisada una vez al mes) o se comprometa a utilizar, y ser capaz de cumplir con una efectiva anticoncepción sin interrupciones, 28 días antes de comenzar el medicamento de estudio, durante el período de tratamiento (incluyendo los periodos de interrupción), y durante los 28 días posteriores a la interrupción definitiva del tratamiento en estudio.

    11. Los pacientes varones recibiendo Lenalidomida deberán?:
    Practicar una completa abstinencia sexual o aceptar el uso de condón durante el contacto sexual con una mujer embarazada o en edad fértil, mientras esté participando en el estudio, durante los periodos de interrupción del tratamiento y al menos, 28 días tras la discontinuación definitiva del medicamento, aunque le hubiera sido practicada vasectomía eficaz.
    Estar de acuerdo con no donar semen durante la terapia con el medicamento de estudio y por 28 días tras la discontinuación definitiva del mismo.

    12. Todos los pacientes que reciban Lenalidomida deberán:
    Tener conocimiento del potencial riesgo teratogénico de la droga de estudio.
    Estar de acuerdo con no donar sangre mientras se esté en tratamiento ni por los 28 días tras la discontinuación definitiva del mismo.
    Estar de acuerdo con no compartir su medicación con ninguna persona.
    Estar de acuerdo con el asesoramiento sobre las precauciones contra el embarazo y el riesgo de exposición del feto.
    Las mujeres deberán estar de acuerdo de no practicar la lactancia materna durante su participación y por los 28 días tras la discontinuación definitiva del tratamiento de estudio.

    13. Para todos los pacientes tratados con Rituximab:
    Las mujeres no deberán emplear la lactancia materna y deberán hacer uso de un método anticonceptivo efectivo con el fin de evitar el embarazo y acceder a no quedarse embarazadas durante su participación en el ensayo y los 6 meses posteriores.

    Los hombres deberán comprometerse a no tener hijos durante su participación en el estudio y durante los 6 meses posteriores.
    E.4Principal exclusion criteria
    -Clinical evidence of transformed lymphoma by investigator assessment
    -Grade 3b follicular lymphoma
    -Patients taking corticosteroids during the last 4 weeks
    -Major surgery within 28 days prior to signing informed consent
    -Seropositive for or active viral infection with hepatitis B virus (HBV)
    -Known seropositive for, or active infection hepatitis C virus (HCV)
    -Known seropositive for, or active viral infection with HIV
    -Life expectancy < 6 months
    -Known sensitivity or allergy to murine products
    -Prior history of malignancies, unless the subject has been free of the disease for ? 10 years. Exceptions include a history of previously treated Localized non-melanoma skin cancer or Carcinoma in situ of the cervix
    -Prior use of lenalidomide
    -Neuropathy > Grade 1
    -Presence or history of CNS involvement by lymphoma
    -Patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis
    -Uncontrolled intercurrent illness
    -Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
    -Pregnant or lactating females
    -Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, or which confounds the ability to interpret data from the study.
    1. Evidencia clínica de linfoma transformado, asesorado por el investigador.

    2. Linfoma folicular Grado 3b.

    3. Pacientes en tratamiento con corticosteroides durante las últimas 4 semanas, excepto si administrados en una dosis equivalente a < 10 mg/día Prednisona (en estas 4 semanas).

    4. Cirugía mayor (excepto para biopsia de nódulos linfáticos) en los 28 días previos a la firma del consentimiento informado.

    5. Ser seropositivo para/presentar una infección vírica activa del virus de la hepatitis B (VHB):
    ? HBsAg positivo
    ? HBsAg negativo, anti-HBs positivo y/o anti-HBc positivo y DNA viral detectable
    Nota:
    ? Los pacientes que sean HBsAg negativo, anti-HBs positivo y/o anti-HBc positivo pero con DNA viral negativo serán elegibles.
    ? Los pacientes seropositivos debido a historial de vacunación contra la hepatitis B serán también elegibles.

    6. Seropositividad conocida para/ con infección activa con el virus de la hepatitis C (VHC).

    7. Seropositividad conocida para/ con infección activa con el virus de la inmunodeficiencia humana adquirida (VIH).

    8. Esperanza de vida < 6 meses.

    9. Sensibilidad conocida o alergia a los productos murinos.

    10. Historial previo de otras enfermedades malignas distintas del linfoma folicular, exceptuando si el paciente ha estado libre de enfermedad por un tiempo ? 10 años. Otras excepciones incluyen un historial de:
    a. Cáncer de piel localizado tipo no-melanoma
    b. Carcinoma de cérvix in situ
    Que ya hayan sido previamente tratados

    11. Uso previo de Lenalidomida.

    12. Neuropatía > Grado 1.

    13. Presencia o historial de infiltración del linfoma al SNC.

    14. Pacientes con alto riesgo de eventos tromboembólicos que no estén dispuestos a tomar profilaxis.

    15. Cualquiera de las siguientes anormalidades de laboratorio:
    ? Aspartato transaminasa en suero (AST/SGOT) o alanina transaminasa (ALT/SGPT) > 3x superior al límite de normalidad (ULN), excepto en pacientes con infiltración del linfoma al hígado o páncreas
    ? Bilirubina total > 2.0 mg/dl (34 µmol/L) excepto en los casos de Síndrome de Gilberts e infiltración del linfoma al hígado
    ? Aclaramiento de creatinina < 30 mL/min

    16. Enfermedad intercurrente no controlada.

    17. Cualquier condición médica grave, anormalidad de laboratorio o enfermedad psiquiátrica que impida al paciente la firma del consentimiento informado.

    18. Mujeres embarazadas o lactantes.

    19. Cualquier condición, incluyendo la presencia de anormalidades de laboratorio, que pongan al paciente en un riesgo inaceptable al participar en el estudio o que pueda confundir la capacidad de interpretación de los resultados del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    The tumor response data will be assessed by the IRC using the IWG (Cheson 1999) criteria. Based on the CT/MRI schedule, any assessments in a time window of 120 weeks ± 4 weeks are qualified as the 120 weeks assessments. If two or more assessments are performed in this time window, the assessment with the least favorable response will be used.
    PFS is an accepted endpoint of clinical benefit for previously untreated FL patient and was the basis for the recent approval of rituximab maintenance in this population (Salles 2011). The disease progression status will be assessed by IRC using the IWG (Cheson 1999) criteria. PFS is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause. If a patient has not progressed or died, PFS will be censored at the time of last visit with adequate assessment. If a patient received other anti-cancer treatment for follicular lymphoma before progression, the CT/MRI assessments should continue as scheduled until disease progression or death which will be counted as events.
    Las covariables de eficacia primarias son la tasa de respuesta completa (RC / RCnc) y SLP (supervivencia libre de progresión).
    E.5.1.1Timepoint(s) of evaluation of this end point
    For the co-primary endpoint of the complete response (CR/CRu) rate at 120 weeks, one interim analysis and one primary analysis is pre-planned. The interim analysis will be performed for the first 200 patients, and the primary analysis for co-primary endpoint of complete response (CR/CRu) will be performed for the total of 644 patients. The purpose of the interim analysis is to check for futility to see if the trial needs to stop early.

    Moreover, a first futility analysis will be done to evaluate the complete response (CR/CRu) rate as determined by IRC at 6 months of treatment for the first 200 patients.
    PFS will be compared between the two treatment arms when the required 456 progress/relapse/death events are observed
    La covariable tasa de respuesta completa (RC/RCno confirmada) se medirá a las 120 semanas; (realizándose un análisis intermedio cuando se hayan alcanzado los 200 primeros pacientes y un segundo análisis intermedio a los 644 pacientes)
    E.5.2Secondary end point(s)
    ?Event Free Survival (EFS)
    ?Time to Next Anti-Lymphoma Treatment (TTNLT),
    ?Overall Survival (OS)
    - Supervivencia Libre de Eventos (SLE)
    - Tiempo hasta el próximo tratamiento contra el linfoma (TTNLT)
    - Supervivencia Global (SG)
    E.5.2.1Timepoint(s) of evaluation of this end point
    (EFS) will be measured from the date of randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause.
    (TTNLT) will be measured from the date of randomization to the date of first documented administration of any new anti-lymphoma treatment (chemotherapy, radiotherapy, radio-immunotherapy, immunotherapy).
    (OS) will be measured from date of randomization to the date of death. Patients who die, regardless of the cause of death, will be considered to have had an event. Patients who withdraw consent for the study will be considered censored at the time of withdrawal.
    SLE se medirá desde la fecha de randomización a la fecha en que se haya reportado progresión, relapso, inicio de un nuevo tratamiento para el linfoma o muerte por cualquier causa.

    TTNLT se medirá desde la fecha de randomización hasta la fecha de la primera administración de terapia contra linfoma (quimioterapia, radioterapia, inmunoterapia, radio-inmunoterapia)

    SG se medirá desde la fecha de randomización hasta la fecha de muerte.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Quality of life
    Calidad de vida
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 EEA120
    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
    Czech Republic
    France
    Germany
    Italy
    New Zealand
    Portugal
    Spain
    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 visit of the last subject undergoing the trial
    Última visita de estudio del último paciente participante
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years13
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years13
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 550
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 200
    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 630
    F.4.2.2In the whole clinical trial 750
    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)
    Patients will be treated according to local practice
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-08-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-06-17
    P. End of Trial
    P.End of Trial StatusOngoing
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