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    Summary
    EudraCT Number:2015-001999-22
    Sponsor's Protocol Code Number:GO29834
    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:2016-01-04
    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 number2015-001999-22
    A.3Full title of the trial
    A PHASE Ib/II STUDY EVALUATING THE SAFETY AND EFFICACY OF OBINUTUZUMAB IN COMBINATION WITH POLATUZUMAB VEDOTIN
    AND LENALIDOMIDE IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR OR DIFFUSE LARGE B-CELL LYMPHOMA
    ESTUDIO DE FASE Ib/II PARA EVALUAR LA SEGURIDAD Y EFICACIA DE OBINUTUZUMAB EN COMBINACIÓN CON POLATUZUMAB VEDOTIN Y LENALIDOMIDA EN PACIENTES CON LINFOMA FOLICULAR O DIFUSO DE LINFOCITOS B GRANDES RECIDIVANTE O RESISTENTE
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Safety and Efficacy of Obinutuzumab in Combination with Polatuzumab Vedotin and Lenalidomide in Patients with Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
    Un estudio para evaluar la seguridad y eficacia de Obinutuzumab en combinación con Polatuzumab Vedotin y lenalidomida en pacientes con con linfoma folicular o difuso de linfocitos B grandes recidivante o resistente
    A.4.1Sponsor's protocol code numberGO29834
    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 SponsorF. Hoffmann-La Roche Ltd.
    B.1.3.4CountrySwitzerland
    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 supportGenentech Inc. c/o F. Hoffmann La Roche Ltd.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGenentech Inc. c/o F. Hoffmann La Roche Ltd.
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number34913257300
    B.5.6E-mailglobal.rochegenentechtrials@roche.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namepolatuzumab vedotin
    D.3.2Product code DCDS4501A
    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 INNPOLATUZUMAB VEDOTIN
    D.3.9.3Other descriptive nameDCDS4501A
    D.3.9.4EV Substance CodeSUB177827
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number170
    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 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: 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 Gazyvaro
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited, UK
    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.3.4Pharmaceutical 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 INNobinutuzumab
    D.3.9.1CAS number 949142-50-1
    D.3.9.3Other descriptive nameOBINUTUZUMAB
    D.3.9.4EV Substance CodeSUB32751
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 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 Yes
    D.3.11.13.1Other medicinal product typeGazyvaro is is a humanized and glycoengineered monoclonal antibody (mAB)
    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 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.3.4Pharmaceutical 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: 4
    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.3.4Pharmaceutical 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: 5
    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.3.4Pharmaceutical 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.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
    Relapsed or refractory, follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL)
    LINFOMA FOLICULAR O DIFUSO DE LINFOCITOS B GRANDES RECIDIVANTE O RESISTENTE
    E.1.1.1Medical condition in easily understood language
    FL is a low grade tumor that develops slowly and DLBCL is an aggressive tumor that develops rapidly
    LF es un tumor de bajo grado que se desarrolla lentamente y LDLBG es un tumor agresivo que se desarrolla rápidamente
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10012857
    E.1.2Term Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) refractory
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10012855
    E.1.2Term Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation)
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10012856
    E.1.2Term Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) recurrent
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. To determine the recommended Phase II dose (RP2Ds) for polatuzumab vedotin (Pola) and lenalidomide (Len) when given in combination with a fixed dose of obinutuzumab on the basis of incidence of dose limiting toxicities (DLTs) during the first cycle of study treatment
    2. To evaluate the safety and tolerability of obinutuzumab+ Pola + Len based on nature, frequency, severity, timing of adverse events and DLTs, changes in vital signs, electrocardiogram (ECGs), and clinical laboratory results during and following study treatment administration
    3. To evaluate the efficacy of induction treatment with obinutuzumab + Pola + Len based on complete response (CR) at end of induction (EOI), on the basis of positron emission tomography computerized tomography (PET CT) scans
    1. Determinar las dosis recomendadas en la fase II (DRF2) de polatuzumab vedotin y lenalidomida administrados en combinación con una dosis fija de obinutuzumab sobre la base de la incidencia de toxicidad limitante de la dosis (TLD) durante el primer ciclo de tratamiento del estudio.
    2. Evaluar la seguridad y tolerabilidad de G+ Pola + Len sobre naturaleza, frecuencia, intensidad y momento de aparición de los acontecimientos adversos, incluida la TLD, alteraciones en las constantes vitales, los ECG y los resultados de pruebas analíticas durante y después de la administración del tratamiento del estudio
    3. Evaluación de la eficacia del tratamiento de inducción con G + Pola + Len basado en la respuesta completa (RC) al fin de la inducción (FI) sobre la base de tomografías de emisión positrónica (TEP) y las tomografías computarizadas (TC)
    E.2.2Secondary objectives of the trial
    1. To evaluate the efficacy of induction treatment with obinutuzumab + Pola + Len based on CR at EOI, as determined by the investigator on the basis of PET-CT scans or CT scans alone, objective response (defined as a CR or PR at EOI) determined by the IRC and the Investigator on the basis of PET CT scans or CT scans alone, best response of CR or PR during the study determined by the Investigator on the basis of CT scans alone
    2. To characterize the pharmacokinetic profiles of obinutuzumab + Pola + Len when given in combination based on the observed serum concentration of obinutuzumab, serum and plasma concentrations of Pola and its relevant analytes, and plasma concentration of Len at specified time points
    3. To evaluate the immune response to obinutuzumab and to Pola based on incidence of human anti-human antibodies (HAHA) to obinutuzumab and anti-therapeutic antibody (ATA) to Pola during the study relative to the prevalence of HAHAs and ATAs at baseline, respectively
    1. Evaluar la eficacia de del tto de inducción con G + Pola + Len sobre la base del RC al FI determinada por el IP a partir de las TEP-TC o de las TC exclusivamente, respuesta objetiva (definida como RC o RP) al FI determinada por el CIR y el IP a partir de las TEP-TC o de las TC exclusivamente, Mejor respuesta de RC o RP durante el estudio, determinada por el IP a partir de las TC exclusivamente
    2. Caracterizar los perfiles perfiles FC del obi, el pola vedotin y la lenalidomida administrados en combinación basados en la concentración sérica de obi., concentración sérica y plasmática de pola y los analitos relevantes y la concentración plasmática de lenalidomida observada en los puntos temporales especificados.
    3.3. Evaluar la respuesta inmunitaria al obi y al pola sobre la base de la Incidencia de anticuerpos antihumanos humanos (HAHA) contra el obi y anticuerpos antiterapéuticos (AAT) contra el pola durante el estudio en relación con la prevalencia de HAHA y AAT al inicio respect
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Age greater than or equal to (>=) 18 years
    - Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
    - For patients enrolled in the dose-escalation phase (DEP) and expansion phase (EP): Relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
    - For patients enrolled in the EP: Relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen in patients who are not eligible for autologous stem-cell transplantation or who have experienced disease progression following treatment with high-dose chemotherapy plus autologous stem-cell transplantation
    - Fluorodeoxyglucose (FDG)-avid lymphoma
    - At least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan or magnetic resonance imaging [MRI])
    - Agreement to abstain from donating blood during the treatment period for 28 days after the last study dose
    - For women of childbearing potential: Agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period and for at least 18 months after the last dose of study treatment
    - For men: Agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
    - Edad >= 18 años
    - Estado funcional 0, 1 o 2 del Grupo Oncológico Cooperativo de la Costa Este
    - Para los pacientes incluidos en la fase de aumento escalonado de la dosis: LF recidivante o resistente tras un tratamiento con al menos un régimen de quimioinmunoterapia que incluya un anticuerpo monoclonal anti-CD20 y para el que no haya ninguna opción terapéutica más adecuada a criterio del investigador
    - Para los pacientes incluidos en la fase de ampliación: LDLBG recidivante o resistente tras un tratamiento con al menos un régimen de quimioinmunoterapia en pacientes que no son aptos para trasplante autólogo de células madre o que han experimentado progresión de la enfermedad tras el tratamiento con quimioterapia en dosis altas más trasplante autólogo de células madre
    - Linfoma con avidez por fluorodesoxiglucosa
    - Al menos una lesión mensurable en dos dimensiones (> 1,5 cm en su mayor diámetro según TC o resonancia magnética)
    - Compromiso de abstenerse de donar sangre durante el período de tratamiento y los 28 días posteriores a la última dosis de tratamiento del estudio
    - En las mujeres fértiles: compromiso de practicar la abstinencia sexual (no mantener relaciones sexuales) o el uso de dos métodos anticonceptivos adecuados que incluyan al menos un método con un índice de fallo de < 1 % anual durante al menos 28 días antes del día 1 del ciclo 1, durante el período de tratamiento (incluidos los períodos de interrupción del tratamiento) y al menos 18 meses después de la última dosis de tratamiento del estudio
    - En los hombres: compromiso de practicar la abstinencia sexual (no mantener relaciones sexuales) o el uso de métodos anticonceptivos y compromiso de no donar esperma
    E.4Principal exclusion criteria
    - Known CD20-negative status at relapse or progression
    - Central nervous system lymphoma or leptomeningeal infiltration
    - Prior allogeneic stem-cell transplantation (SCT)
    - Completion of autologous SCT within 100 days
    - History of resistance to lenalidomide or response duration of <1 year
    - Prior standard or investigational anti cancer therapy
    - Clinically significant toxicity from prior therapy that has not resolved to Grade <=2 (per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0)
    - Treatment with systemic immunosuppressive medications
    - History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies
    - Known sensitivity or allergy to murine products
    - History of erythema multiforme, Grade >=3 rash, or desquamation (blistering)
    - Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody
    - History of progressive multifocal leukoencephalopathy
    - Contraindication to treatment for thromboembolism (TE) prophylaxis
    - Life expectancy <3 months
    - CD20 negativo en la recidiva o progresión
    - Linfoma del sistema nervioso central o infiltración leptomeníngea
    - Trasplante de células madre (TCM) alógeno previo
    - Realización de TCM autólogo en los 100 días previos al día 1 del ciclo 1
    - Antecedentes de resistencia a la lenalidomida o respuesta de < 1 año
    - Tratamiento anticanceroso estándar o experimental previo
    - Toxicidad clínicamente significativa de un tratamiento previo que no se haya resuelto hasta el grado <= 2 (según los CTCAE NCI, versión 4.0)
    - Tratamiento con inmunodepresores sistémicos
    - Antecedentes de reacción alérgica o anafiláctica grave a anticuerpos monoclonales humanizados o murinos
    - Sensibilidad o alergia conocida a los productos murinos
    - Antecedentes de eritema multiforme, exantema de grado >= 3 o descamación (vesiculación)
    - Antígeno de superficie del virus de la hepatitis B, anticuerpo nuclear contra el virus de la hepatitis B o anticuerpo positivo contra el virus de la hepatitis C
    - Antecedentes de leucoencefalopatía multifocal progresiva
    - Contraindicación para el tratamiento profiláctico de TE
    - Esperanza de vida < 3 meses
    E.5 End points
    E.5.1Primary end point(s)
    Safety:
    1. Incidence of dose-limiting toxicities (DLTs) during Cycle 1 of study treatment
    2. Incidence of adverse events
    3. Changes in vital signs, ECG and clinical laboratory results

    Efficacy:
    4. CR at EOI, as determined by the IRC on the basis of PET-CT scans
    Seguridad:
    1. Incidencia de toxicidad limitante de la dosis (TLD) durante el primer ciclo de tratamiento del estudio
    2. Incidencia de acontecimientos adversos
    3. Alteraciones en las constantes vitales, los ECG y los resultados de pruebas analíticas

    Eficacia:
    4. RC al FI, determinada por el CIR a partir de las TEP-TC
    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety:
    1. From Day 1 (D1) to D28 of Cycle 1 (C1)
    2. From screening up to 5 Years
    3. From screening up to 35 days after the last dose of maintenance/consolidation treatment

    Efficacy:
    4. 6?8 weeks after Day 1 of the last induction cycle
    Seguridad:
    1. Del Día 1 (D1) al D28 del Ciclo 1 (C1)
    2. Desde el sreening hasta un máximo de 5 años
    3. Desde el screanign hasta un máximo de 35 días después de la última dosis de matenimiento/consolidación del tratamiento

    Eficacia:
    4. 6-8 semanas despúes del Dia 1 del última ciclo de inducción
    E.5.2Secondary end point(s)
    Efficacy:
    1. CR at EOI, as determined by the investigator on the basis of PET-CT scans
    2. CR at EOI, as determined by the investigator on the basis of CT scans alone
    3. Objective response (defined as a CR or PR) at EOI, as determined by the IRC and by the investigator on the basis of PET-CT scans
    4. Objective response (defined as a CR or PR) at EOI, as determined by the IRC and by the investigator on the basis of CT scans alone
    5. Best response of CR or PR during the study, as determined by the investigator on the basis of CT scans alone

    PK:
    6. Observed serum obinutuzumab concentration at specified time points
    7. Observed serum and plasma concentrations of Pola and its relevant analytes at specified time points
    8. Observed plasma Len concentration at specified time points

    Immunogenicity
    9. Incidence of human anti-human antibodies (HAHA) to obinutuzumab during the study relative to the prevalence of HAHAs at baseline
    10. Incidence of anti-therapeutic antibody (ATA) to Pola during the study relative to the prevalence of ATAs, at baseline
    Eficacia:
    1. RC al FI, determinada por el investigador a partir de las TEP-TC
    2. RC al FI, determinada por el investigador a partir de las TC exclusivamente
    3. Respuesta objetiva (definida como RC o RP) al FI, determinada por el CIR y el investigador a partir de las TEP-TC
    4. Respuesta objetiva (definida como RC o RP) al FI, determinada por el CIR y el investigador a partir de las TC exclusivamente
    5. Mejor respuesta de RC o RP durante el estudio, determinada por el investigador a partir de las TC exclusivamente

    FC:
    6. Concentración sérica de obinutuzumab observada en los puntos temporales especificados
    7. Concentración sérica y plasmática de polatuzumab vedotin y los analitos relevantes en los puntos temporales especificados
    8. Concentración plasmática de lenalidomida observada en los puntos temporales especificados

    Inmunogenicidad
    9. Incidencia de anticuerpos antihumanos humanos (HAHA) contra el obinutuzumab durante el estudio en relación con la prevalencia de HAHA al inicio
    10. Incidencia de anticuerpos antiterapéuticos (AAT) contra el polatuzumab vedotin durante el estudio en relación con la prevalencia de AAT al inicio
    E.5.2.1Timepoint(s) of evaluation of this end point
    Efficacy:
    1-4. 6-8 weeks after Day 1 of the last induction cycle
    5. Up to 5 years

    PK:
    6. Dose escalation phase (DP) and expansion phase (EP): C1D1, C2D1, C4D1, and C6D1; Maintenance phase (MP) and consolidation phase (CP): Month (M) 1D1, (M7D1, M13D1and M19D1 only for MP), at treatment discontinuation (TD), 120 days and 1 2 years after the last dose of obinutuzumab
    7. DP and EP: C1D1, C1D8, C1D15, C2D1, C4D1, C6D1; MP and CP: at TD, 120 days and 1 2 years after the last dose of Pola
    8. DP and EP: C1D1, C1D15, C6D1

    Immunogenicity:
    9. DP and EP: on C1D1, C6D1; MP and CP: at TD, 120 days and 1 2 years after the last dose of obinutuzumab
    10. DP and EP: C1D1, C2D1, C4D1; MP and CP: at TD, 120 days and 1 2 years after the last dose of Pola
    Eficacia:
    1-4. 6-8 semanas después del Día 1 del último ciclo de inducción
    5. Hasta 5 años

    FC:
    6. Fase de escalonado de la dosis (ED) y fase de expansión (FE): C1D1, C2D1, C4D1 y C6D1; Fase de mantenimiento (FM) y fase de consolidación (FC): Mes (M) 1D, (M7D1, M13D1and M19D1 solo FM), a la discontinuación del tratamiento (DT), 120 días y 1 2 años tras la última dosis de obinutuzumab
    7. ED y FE: C1D1, C1D8, C1D15, C2D1, C4D1, C6D1; FM and FC: at DT, 120 días y 1 2 años tras la última dosis de Pola
    8. ED y FE: C1D1, C1D15, C6D1

    Inmunogenicidad
    9. ED y FE: en C1D1, C6D1;FM y FC: al DT, 120 días y 1 2 años después de la última dosis de obinutuzumab
    10. ED y FE: C1D1, C2D1, C4D1; FM y FC: al DT, 120 días y 1 2 años después de la última dosis de pola
    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 No
    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
    Immunogenicity
    Inmunogenecidad
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned12
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA19
    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
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    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
    The end of this study is defined as the time when both of the following criteria are met:
    ? All enrolled patients with FL have completed or discontinued study treatment (including induction treatment and maintenance treatment as applicable).
    ? All enrolled patients with DLBCL have been followed for at least 1 year after they have completed or discontinued study treatment (including induction treatment and consolidation treatment as applicable).
    El fin del estudio se define como el momento en que se cumplen los dos criterios siguientes:
    - Todos los pacientes con LF incluidos han finalizado o suspendido el tto del estudio (incluidos el tratamiento de inducción y el tratamiento de mantenimiento, según proceda).
    - Todos los pacientes con LDLBG han sido objeto de seguimiento durante al menos 1 año tras la finalización o suspensión del tratamiento del estudio (incluidos el tto de inducción y el tto de consolidación, según proceda).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    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 years5
    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: 46
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    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 state46
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 92
    F.4.2.2In the whole clinical trial 116
    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)
    Currently, the Sponsor does not have any plans to provide obinutuzumab and polatuzumab vedotin or any other study treatments or interventions to patients who have completed the study. The Sponsor will evaluate whether to continue providing obinutuzumab and polatuzumab vedotin in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, available at the following Web site:
    http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    En la actualidad, el promotor no tiene previsto facilitar obinutuzumab, polatuzumab vedotin ni ningún otro tto o intervención del estudio a los pacientes que hayan finalizado el estudio.
    El promotor estudiará si continúa suministrando obinutuzumab y pola vedotin de conformidad con la política global de Roche en materia de acceso continuado a los medicamentos en investigación, disponible en la página web siguiente:
    http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    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 Decision2016-02-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-02-02
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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