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    Summary
    EudraCT Number:2014-004688-19
    Sponsor's Protocol Code Number:MOR208C203
    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:2015-07-31
    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 number2014-004688-19
    A.3Full title of the trial
    A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined with MOR00208 in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL)
    Estudio de fase II, multicéntrico, sin enmascaramiento y de un solo grupo para evaluar la seguridad y eficacia de lenalidomida en combinación con MOR00208 en pacientes con linfoma difuso de células B grandes recidivante o resistente al tratamiento (LDCBG R-R)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical study to evaluate the safety and effectiveness of lenalidomide combined with MOR00208 in adult patients with diffuse large B cell lymphoma that has progressed after previous treatment
    Estudio clínico para evaluar la seguridad y eficacia de lenalidomida combinada con MOR00208 en pacientes adultos con linfoma difuso de células B grandes que han progresado después del tratamiento anterior.
    A.4.1Sponsor's protocol code numberMOR208C203
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02399085
    A.5.4Other Identifiers
    Name:US IND NumberNumber:114,856
    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 SponsorMorphoSys AG
    B.1.3.4CountryGermany
    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 supportMorphoSys AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMorphoSys AG
    B.5.2Functional name of contact pointClinical Program Lead Oncology
    B.5.3 Address:
    B.5.3.1Street AddressLena-Christ-Strasse 48
    B.5.3.2Town/ cityMartinsried/Planegg
    B.5.3.3Post codeD-82152
    B.5.3.4CountryGermany
    B.5.4Telephone number+34914322630
    B.5.5Fax number+4989899275208
    B.5.6E-mailinfo@morphosys.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 numberEU/3/14/1424-EMA/OD/215/14
    D.3 Description of the IMP
    D.3.2Product code MOR00208
    D.3.4Pharmaceutical form Lyophilisate 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 INNno INN assigned
    D.3.9.2Current sponsor codeMOR00208
    D.3.9.3Other descriptive nameMOR00208
    D.3.9.4EV Substance CodeSUB91252
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 Revlimid(R)
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene
    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.3.4Pharmaceutical 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 typerange
    D.3.10.3Concentration number5 to 25
    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 Diffuse Large B-Cell Lymphoma (R-R DLBCL)
    Linfoma difuso de células B grandes recidivante o resistente (LDCBG R-R)
    E.1.1.1Medical condition in easily understood language
    Medical condition: Diffuse lymph nodes cancer attacking large antibody producing cells that has progressed after previous treatment
    Condición Médica:
    Cáncer difuso de los ganglios linfáticos que ataca las células grandes productoras de anticuerpos, y que ha progresado tras el tratamiento anterior
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10012818
    E.1.2Term Diffuse large B-cell lymphoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the activity of a combination of LEN with MOR00208 in terms of objective response rate (ORR = complete response [CR] + partial response [PR]) in adult patients with R-R DLBCL.
    Determinar la actividad de una combinación de LEN y MOR00208 en cuanto a la tasa de respuesta objetiva (TRO = respuesta completa [RC] + respuesta parcial [RP]) en pacientes adultos con LDCBG R-R.
    E.2.2Secondary objectives of the trial
    1.To determine the disease control rate (DCR = CR + PR + stable disease [SD])
    2.To determine the duration of response (DoR)
    3.To determine the activity of a combination of LEN with MOR00208 in terms of progression-free survival (PFS)
    4.To determine the overall survival (OS)
    5.To determine time to progression (TTP)
    6.To determine the time to next treatment (TTNT)
    7.To determine the safety of LEN combined with MOR00208 assessed according to the frequency and severity of adverse events (AEs)
    8.To assess the potential immunogenicity of MOR00208
    9.To assess the pharmacokinetics (PK) of MOR00208
    10.To make a preliminary evaluation of ORR, DCR, DoR, PFS, OS, TTP and TTNT in patients treated with a combination of LEN plus MOR00208 in cohorts with a ?low risk?, ?low-intermediate?, ?high-intermediate? and ?high? International Prognostic Index (IPI)
    For full list please refer to the protocol.
    1. Determinar la tasa de control de la enfermedad (DCR = RC + RP + enfermedad estable [EE])
    2. Determinar la duración de la respuesta (DR)
    3. Determinar la actividad de una combinación de LEN y MOR00208 en cuanto a la supervivencia sin progresión (SSP)
    4. Determinar la supervivencia general (SG)
    5. Determinar el tiempo hasta la progresión (THP)
    6. Determinar el tiempo hasta el siguiente tratamiento (THST)
    7. Determinar la seguridad de LEN combinado con MOR00208 evaluada de acuerdo con la frecuencia e intensidad de los acontecimientos adversos (AA)
    8.Evaluar la posible inmunogenicidad de MOR00208
    9. Evaluar la farmacocinética (FC) de MOR00208
    10. Realizar una evaluación preliminar de la TRO, la DCR, la DR, la SSP, la SG, el THP y el THST en pacientes tratados con una combinación de LEN y MOR00208 en cohortes con un Índice de pronóstico internacional (IPI) de ?riesgo bajo?, ?bajo-intermedio?, ?alto-intermedio? y ?alto?
    Remítase al protocolo para ver la lista completa.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 18-80 years old
    2. Histologically confirmed diagnosis of DLBCL according to the Revised European American Lymphoma/World Health Organization (REAL/WHO) classification. Patients with evidence of histological transformation to DLBCL from indolent NHL are also eligible
    3. Recent tumour tissue for central pathology review and correlative studies must be provided as an adjunct to participation in this study. The only exception is the availability of tumour tissue acquired ?3 years prior to screening for this protocol
    4. Patients must have:
    a) relapsed and/or refractory disease as defined in the protocol
    b) at least one bidimensionally measurable disease site. The lesion must have a greatest transverse diameter of ?1.5 cm and greatest perpendicular diameter of ? 1.0 cm at baseline
    c) received at least one, but no more than two previous systemic regimens for the treatment of DLBCL and one therapy line must have included a CD20-targeted therapy (e.g. RTX)
    d) an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
    5. Patients not considered in the opinion of the investigator eligible, or patients unwilling to undergo intensive salvage therapy including ASCT because of, but not limited to, advanced age, comorbidities, impossibility or, refusal to perform ASCT. Documentation of the reason for a patient's ineligibility must be provided in the patient's source data.
    Laboratory values
    6. Patients must meet the following laboratory criteria at screening:
    a) absolute neutrophil count (ANC) ? 1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL as demonstrated by recent bone marrow aspiration and bone marrow biopsy)
    b) platelet count ? 90 × 109/L (unless secondary to bone marrow involvement by DLBCL as demonstrated by recent bone marrow aspiration and bone marrow biopsy)
    c) total serum bilirubin ? 2.5 × upper limit of normal (ULN) or ? 3 × ULN in cases of documented liver involvement
    d) alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) ? 3 × ULN or <5 × ULN in cases of documented liver involvement
    e) serum creatinine clearance must be ? 60 mL/minute either measured or calculated using a standard Cockcroft and Gault formula (Cockroft and Gault, 1976).

    General Provisions
    7. Females of childbearing potential (FCBP) must:
    a) not be pregnant as confirmed by a negative serum pregnancy test at screening and a medically supervised urine pregnancy test prior to starting study therapy
    b) refrain from breastfeeding and donating blood or oocytes during the course of the study and for 3 months after the last dose of study medication. Restrictions concerning blood donation apply as well to females who are not of childbearing potential
    c) agree to ongoing pregnancy testing during the course of the study, and after study therapy has ended. This applies even if the patient practices complete and continued sexual abstinence
    d) commit to continued abstinence from heterosexual intercourse if it is in accordance with her lifestyle (which must be reviewed on a monthly basis) or agree to use and be able to comply with the use of effective contraception without interruption during the study and for 3 months after the last dose of study medication
    8. Males must use an effective barrier method of contraception without interruption, refrain from donating blood or sperm during the study participation and for 3 months after the last dose of study medication if the patient is sexually active with a FCBP
    9. In the opinion of the investigator the patients must:
    a) be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events
    b) be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations
    c) not have a history of noncompliance in relation to medical regimens or be considered potentially unreliable and/or uncooperative
    d) be able to understand the reason for complying with the special conditions of the pregnancy prevention risk management plan and give written acknowledgement of this.
    1. 18-80 años de edad
    2. Diagnóstico, confirmado histológicamente, de LDCBG de acuerdo con la Clasificación revisada europeo-americana del linfoma/de la Organización mundial de la salud (REAL/WHO). También son aptos los pacientes con signos de transformación histológica de NHL indolente a LDCBG.
    3. Para participar en este estudio se deberá facilitar como complemento tejido tumoral reciente para revisión anatomopatológica central y estudios correlativos. La única excepción se dará cuando se halle disponible tejido tumoral obtenido ? 3 años antes de la selección para este protocolo
    4. Los pacientes deberán:
    a) presentar enfermedad recidivante y/o resistente al tratamiento tal como se definen en el protocolo.
    b) tener como mínimo una localización de la enfermedad medible en dos dimensiones. La lesión deberá tener en el momento inicial del estudio un diámetro transversal superior de ? 1,5 cm, y un diámetro perpendicular superior de ? 1,0 cm
    c) haber recibido como mínimo un régimen sistémico previo, pero no más de dos, para el tratamiento del LDCBG, debiendo haber incluido una de las líneas terapéuticas un tratamiento dirigido contra CD20 (p. ej. RTX)
    d) un estado general de entre 0 y 2 del Grupo oncológico cooperativo del este (ECOG)
    5. Los pacientes que en opinión del investigador no sean aptos para el estudio, o los que no estén dispuestos a someterse a un tratamiento intensivo de rescate que incluya ATCM, por ejemplo a causa de la edad avanzada, de enfermedades concomitantes o de la imposibilidad de, o la negativa a, llevar a cabo el ATCM. En la historia clínica del paciente deberá documentarse la razón de la falta de aptitud del paciente.

    Valores analíticos
    6. En el momento de la selección los pacientes deberán cumplir los siguientes criterios analíticos:
    a) recuento absoluto de neutrófilos (RAN) ? 1,5 × 109/l (salvo si la causa es una afectación de la médula ósea por el LDCBG demostrada por aspiración y biopsia de médula ósea recientes)
    b) recuento de plaquetas ? 90 × 109/l (salvo si la causa es una afectación de la médula ósea por el LDCBG demostrada por aspiración y biopsia de médula ósea recientes)
    c) bilirrubina sérica total ? 2,5 × límite superior de la normalidad (LSN) o ? 3 × LSN en casos de afectación hepática documentada
    d) valores de alanina transaminasa (ALT), aspartato aminotransferasa (AST) y fosfatasa alcalina (FA) ? 3 × LSN o < 5 × LSN en casos de afectación hepática documentada
    e) el aclaramiento de creatinina sérica debe ser ? 60 ml/minuto, tanto si se mide como si se calcula por medio de una fórmula estándar de Cockcroft y Gault (Cockcroft and Gault, 1976).
    Provisiones generales
    7. Las mujeres potencialmente fértiles (MPF) deberán:
    a) no estar embarazadas, lo que se confirmará con una prueba del embarazo en suero con resultado negativo en la selección y una prueba de embarazo en orina con supervisión médica antes de iniciar el tratamiento del estudio
    b) abstenerse de amamantar y de donar sangre u ovocitos durante el curso del estudio y durante los 3 meses siguientes a la última dosis del medicamento del estudio. Las restricciones sobre la donación de sangre se aplican también a las mujeres no fértiles
    c) aceptar someterse a pruebas de embarazo regulares durante el estudio y una vez que haya finalizado el tratamiento del estudio. Esto se aplicará aunque la paciente practique una abstinencia sexual completa y continua
    d) comprometerse a abstenerse de forma continuada de mantener relaciones heterosexuales si eso se corresponde con su estilo de vida (compromiso que deberá revisarse mensualmente), o aceptar, y ser capaz de mantener, el uso de métodos anticonceptivos eficaces sin interrupción durante el estudio y durante los 3 meses siguientes a la última dosis del medicamento del estudio.
    8. Los pacientes varones deberán usar un método anticonceptivo de barrera efectivo sin interrupción, abstenerse de donar sangre o esperma durante su participación en el estudio y durante los 3 meses siguientes a la última dosis del medicamento del estudio, si son sexualmente activos con una MPF
    9. Los pacientes deberán, en opinión del investigador:
    a) poder y estar dispuestos a recibir una profilaxis y/o tratamiento adecuados para los acontecimientos tromboembólicos
    b) ser capaces de entender, dar su consentimiento informado por escrito y cumplir todos los procedimientos, uso de medicamentos y evaluaciones relacionados con el estudio
    c) no tener antecedentes de incumplimiento terapéutico en relación con regímenes médicos ni ser considerados potencialmente poco fiables y/o poco colaboradores
    d) ser capaces de entender el motivo por el que deben cumplir las condiciones especiales del plan de gestión de riesgo y de prevención del embarazo, y aceptarlas por escrito
    E.4Principal exclusion criteria
    1. Patients who have:
    a) any other histological type of lymphoma including primary mediastinal (thymic) large B-cell (PMBL) or Burkitt lymphoma
    b) primary refractory DLBCL or relapsed within period ? 3 months of prior CD20-targeted therapy (e.g. RTX)
    c) a history of "double/triple hit" DLBCL characterised by simultaneous detection of MYC with BCL2 and/or BCL6 translocation(s) defined by fluorescence in situ hybridisation. MYC, BCL2, BCL6 testing prior to study enrolment is not required.

    Exclusionary Previous and current treatment
    2. Patients who have, within 14 days prior to Day 1 dosing:
    a) not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy
    b) undergone major surgery or suffered from significant traumatic injury
    c) received live vaccines.
    d) required parenteral antimicrobial therapy for active, intercurrent infections
    3. Patients who:
    a) have, in the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies
    b) were previously treated with CD19-targeted therapy or IMiDs® (e.g. thalidomide, LEN)
    c) have a history of hypersensitivity to compounds of similar biological or chemical composition to MOR00208, IMiDs® and/or the excipients contained in the study drug formulations
    d) have undergone ASCT within the period ? 3 months prior to signing the informed consent form. Patients who have a more distant history of ASCT must exhibit full haematological recovery before enrolment into the study
    e) have undergone previous allogenic stem cell transplantation
    f) have a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
    g) concurrently use other anticancer or experimental treatments

    Exclusionary Patient´s medical history
    4. Prior history of malignancies other than DLBCL, unless the patient has been free of the disease for ? 5 years prior to screening. Exceptions to the ? 5 years time limit include a history of the following:
    a) basal cell carcinoma of the skin
    b) squamous cell carcinoma of the skin
    c) carcinoma in situ of the cervix
    d) carcinoma in situ of the breast
    e) carcinoma in situ of the bladder
    f) incidental histological finding of prostate cancer (Tumour/Node/Metastasis [TNM] stage of T1a or T1b)
    5. Patients with:
    a) positive hepatitis B and/or C serology.
    b) known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV)
    c) CNS lymphoma involvement ?present or past medical history
    d) history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator's opinion preclude participation in the study or compromise the patient's ability to give informed consent.
    e) history or evidence of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
    f) gastrointestinal abnormalities including the inability to take oral medication, requiring intravenous alimentation, or prior surgical procedure affecting absorption
    1. Pacientes que tengan:
    a) cualquier otro tipo histológico de linfoma, lo que incluye el linfoma de células B grandes mediastínico primario (tímico) (LBMP) o el linfoma de Burkitt
    b) LDCBG primario resistente al tratamiento o recidivado en el período de ? 3 meses después de un tratamiento anterior dirigido contra CD20 (p. ej. RTX)
    c) antecedentes de LDCBG con "doble/triple hit" caracterizado por la detección simultánea de MYC con translocación o translocaciones en BCL2 y/o BCL6 definida(s) por hibridación fluorescente in situ. No son necesarias pruebas para MYC, BCL2 o BCL6 antes de la inscripción en el estudio.

    Tratamiento previo y actual que es causa de exclusión
    2. Pacientes que en los 14 días anteriores a la dosis del día 1:
    a) no hayan interrumpido su tratamiento dirigido contra CD20, quimioterapia, radioterapia, tratamiento oncológico en fase de investigación u otro tratamiento específico para el linfoma
    b) se hayan sometido a una cirugía mayor o hayan sufrido una lesión traumática significativa
    c) hayan recibido vacunas de virus vivos
    d) hayan necesitado tratamiento antimicrobiano por vía parenteral para infecciones intercurrentes activas.
    3. Pacientes que:
    a) en opinión del investigador no se hayan recuperado suficientemente de los efectos tóxicos adversos de tratamientos anteriores
    b) hayan recibido previamente tratamiento dirigido contra CD19 o IMiDs® (p. ej. talidomida, LEN)
    c) tengan antecedentes de hipersensibilidad a compuestos con una composición biológica o química similar a la de MOR00208, IMiDs® y/o los excipientes que contienen las presentaciones del fármaco del estudio
    d) se hayan sometido a un ATCM en el período de ? 3 meses anterior a la firma del formulario de consentimiento informado. Los pacientes que tengan antecedentes más lejanos de ATCM deberán mostrar una recuperación hematológica completa antes de su inscripción en el estudio
    e) se hayan sometido a un trasplante alogénico previo de células madre
    f) tengan un historial de trombosis venosa profunda/embolia, amenaza de tromboembolia o trombofilia conocida, o que en opinión del investigador presenten un riesgo elevado de sufrir un acontecimiento tromboembólico y que no puedan/no estén dispuestos a recibir profilaxis para prevenir los acontecimientos tromboembólicos venosos durante todo el período de tratamiento
    g) reciban de forma concurrente otros tratamientos oncológicos o experimentales.

    Antecedentes médicos del paciente que son causa de exclusión
    4. Antecedentes previos de neoplasias malignas distintas del LDCBG, salvo que el paciente haya estado libre de enfermedad durante ? 5 años antes de la selección. Entre las excepciones al límite temporal de ? 5 años se incluyen los antecedentes de:
    a) carcinoma basocelular cutáneo
    b) carcinoma de células escamosas cutáneo
    c) carcinoma in situ de cérvix
    d) carcinoma in situ de mama
    e)carcinoma in situ de vejiga
    f) hallazgo histológico incidental de cáncer de próstata (estadio T1a o T1b de la clasificación Tumor/Ganglio/Metástasis [TNM]).
    5. Pacientes con:
    a) serología positiva para hepatitis B y/o C
    b) seropositividad conocida para el virus de la inmunodeficiencia humana (VIH), o infección viral activa por VIH
    c) afectación del SNC por linfoma - antecedente médico presente o pasado
    d) antecedentes o signos de enfermedad cardiovascular, del SNC y/u otra enfermedad sistémica, de importancia clínica, que en opinión del investigador descartaría la participación en el estudio o perjudicaría la capacidad del paciente para dar su consentimiento informado
    e) antecedentes o signos de problemas hereditarios raros de intolerancia a la galactosa, deficiencia de lactasa de Lapp o malabsorción de glucosa-galactosa
    f) anomalías digestivas, incluida la incapacidad de tomar medicamentos orales, necesidad de alimentación intravenosa o intervención quirúrgica previa que afecte a la absorción.
    E.5 End points
    E.5.1Primary end point(s)
    Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR))
    Tasa de respuesta objetiva (respuesta completa + respuesta parcial)
    E.5.1.1Timepoint(s) of evaluation of this end point
    after end of the study
    Tras el fin del ensayo
    E.5.2Secondary end point(s)
    1. DCR, DoR, PFS, OS, TTP and TTNT
    2. Incidence and severity of AEs
    3. Determination and characterisation of a potential anti-MOR00208
    antibody formation
    4. PK analysis of MOR00208
    5. Absolute and percentage change from baseline in measurements of B-, T- and NK cell populations
    6. Analysis of exploratory and diagnostic biomarkers (e.g. CD19, CD20, BCL2, and BCL6 expression, CD16 expression on NK cells, ADCC capacity), gene expression profiling for cell of origin subtyping and evaluation of AEs and ORR stratified by Fc?RIIIa and Fc?RIIa polymorphism) are planned to be investigated during the course of the study.
    1. DCR, DR, SSP, SG, THP y THST
    2. Incidencia e intensidad de los AA
    3. Determinación y caracterización de una posible formación de anticuerpos contra MOR00208
    4. Análisis FC de MOR00208
    5. Cambio absoluto y porcentual con respecto al momento inicial en las mediciones de poblaciones de células B, T y NK
    6. Se ha previsto investigar en el curso del estudio análisis de biomarcadores exploratorios y diagnósticos (p. ej., la expresión de CD19, CD20, BCL2 y BCL6, la expresión de CD16 en las células NK, la capacidad de CCDA, el perfilado de la expresión génica para la subtipificación de las células de origen y la evaluación de AA y TRO estratificada por polimorfismo de Fc?RIIIa y Fc?RIIa).
    E.5.2.1Timepoint(s) of evaluation of this end point
    After end of study
    Tras el fin del estudio
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    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.8.2.4Number of treatment arms in the trial1
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA49
    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
    Belgium
    Czech Republic
    France
    Germany
    Hungary
    Italy
    Poland
    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
    LVLS
    Última visita Último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    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 years4
    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: 10
    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 state13
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 70
    F.4.2.2In the whole clinical trial 80
    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)
    No post-treatment provided by sponsor. The treating physician will decide upon adequate treatment of care
    No se contempla un tratamiento tras el estudio por parte del Promotor. El médico del estudio decidirá sobre el tratamiento más adecuado.
    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 Decision2015-09-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-14
    P. End of Trial
    P.End of Trial StatusOngoing
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