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    Summary
    EudraCT Number:2016-004937-26
    Sponsor's Protocol Code Number:GELLC-7
    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:2017-05-29
    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 number2016-004937-26
    A.3Full title of the trial
    A multicenter, non-randomized, open label study to evaluate the efficacy and security of Ibrutinib followed by ofatumumab consolidation in previously untreated patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
    Estudio multicéntrico, no aleatorizado y abierto, para evaluar la eficacia y seguridad de ibrutinib seguido por consolidación con ofatumumab, en pacientes con Leucemia Linfocítica Crónica (LLC) o Linfoma Linfocítico de Células Pequeñas (LLCP) sin tratamiento previo
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the efficacy and safety of ibrutinib and ofatumumab in untreated patients with chronic lymphocytic leukemia or small cell lymphocytic lymphoma.
    Estudio para evaluar la eficacia y seguridad de ibrutinib y ofatumumab en pacientes con leucemia linfocítica crónica o linfona linfocítico de células pequeñas sin tratamiento previo
    A.4.1Sponsor's protocol code numberGELLC-7
    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 SponsorFundación PETHEMA
    B.1.3.4CountrySpain
    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 supportFundación Pethema
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationFundación Pethema
    B.5.2Functional name of contact pointDr. Juan José Lahuerta Palacios
    B.5.3 Address:
    B.5.3.1Street AddressHospital Clínico San Carlos. 2ª Sur. Hematología. -C/ Profesor Martín Lagos s/n.
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28040
    B.5.3.4CountrySpain
    B.5.4Telephone number+3491 779 28 76
    B.5.5Fax number+3491 330 33 12
    B.5.6E-mailpethema@pethema.es
    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 Ofatumumab
    D.2.1.1.2Name of the Marketing Authorisation holderArzerra
    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 nameARZERRA
    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 INNOFATUMUMAB
    D.3.9.1CAS number 679818-59-8
    D.3.9.4EV Substance CodeSUB25221
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number100 to 1000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 IBRUTINIB
    D.2.1.1.2Name of the Marketing Authorisation holderIMBRUVICA
    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 nameIMBRUVICA
    D.3.4Pharmaceutical form
    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 INNIBRUTINIB
    D.3.9.1CAS number 936563-96-1
    D.3.9.2Current sponsor codeIMBRUVICA
    D.3.9.3Other descriptive nameIBRUTINIB
    D.3.9.4EV Substance CodeSUB120863
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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
    Chronic Lymphocytic Leukemia or Lymphocytic Small Cell Lymphoma without previous treatment
    Leucemia Linfocítica Crónica (LLC) o Linfoma Linfocítico de Células Pequeñas (LLCP) sin tratamiento previo
    E.1.1.1Medical condition in easily understood language
    Chronic Lymphocytic Leukemia or Lymphocytic Small Cell Lymphoma
    Leucemia Linfocítica Crónica o Linfoma Linfocítico de Células Pequeñas
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10051812
    E.1.2Term Small cell lymphocytic lymphoma
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10008976
    E.1.2Term Chronic lymphocytic leukemia
    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
    To determine the complete response rate obtained with the sequential combination of Ibrutinib and ofatumumab.
    Patients will receive 12 cycles of ibrutinib. Those obtaining a CR will continue with Ibrutinib alone, whereas patients not obtaining a CR will be treated with Ibrutinib and 6 cycles of ofatumumab. For the primary endpoint of the study, response will be evaluated after two months of completing ofatumumab.
    Determinar la tasa de respuestas completas obtenida con la combinación secuencial de ibrutinib y ofatumumab.
    Los pacientes recibirán 12 ciclos de ibrutinib. Aquellos que alcancen una RC continuarán con ibrutinib únicamente, mientras que los pacientes que no consigan una RC serán tratados con ibrutinib y 6 ciclos de ofatumumab. Para determinar la variable principal, se evaluará la respuesta dos meses después de completar el tratamiento con ofatumumab.
    E.2.2Secondary objectives of the trial
    • Overall response rate, including partial response with lymphocytosis
    • Evaluation of minimal residual disease (MRD)
    • Duration of response and progression-free survival
    • Safety: type, frequency, and severity of adverse events (AEs) and relationship of AEs to ibrutinib or the combination of ibrutinib and ofatumumab
    • Response rate in relationship to molecular and genetic prognostic factors
    • Evaluate biomarkers related to BCR and compensatory signaling pathways and their association with resistance to ibrutinib treatment
    • Immunological recovery
    • Overall survival
    • Tasa global de respuesta, incluyendo la respuesta parcial con linfocitosis
    • Evaluación de la enfermedad mínima residual (EMR)
    • Duración de la respuesta y supervivencia libre de progresión
    • Seguridad: tipo, frecuencia y gravedad de los efectos adversos (EAs) y la relación de los EAs con el ibrutinib o con la combinación de ibrutinib y ofatumumab
    • Tasa de respuesta en relación con los factores pronósticos moleculares y genéticos
    • Evaluación de los biomarcadores relacionados con el BCR y con posibles vías de señalización compensatorias, y su asociación con la resistencia al tratamiento con ibrutinib
    • Recuperación inmunológica
    • Supervivencia global
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Physically fit patients with treatment-naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
    1. Adult patients with previously untreated CLL or SLL defined following IWCLL criteria (Hallek, 2008).
    2. Must understand and voluntarily sign an informed consent form.
    3. Age ≥ 18 years at the time of signing the informed consent form and must be able to adhere to the study visit schedule and other protocol requirements.
    4. Must have a documented diagnosis of CLL or SLL [IWCLL guidelines for diagnosis and treatment of CLL (Hallek, 2008)] meeting at least one of the following criteria:
    • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia.
    • Massive (i.e. > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
    • Massive nodes (i.e. > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
    • Progressive lymphocytosis with an increase of > 50% over a 2 month period, or lymphocyte doubling time (LDT) of less than 6 months.
    • A minimum of any one of the following disease-related symptoms: unintentional weight loss ≥ 10% within the previous 6 months, significant fatigue (i.e., ECOG PS 2; cannot work or unable to perform usual activities), fevers of greater than 38.0° C or 100.5F for 2 or more weeks without other evidence of infection, or night sweats for more than 1 month without evidence of infection.
    5. Physically fit patients defined as CIRS < 6.
    6. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.
    7. All sexually active subjects (male and female) must use accepted methods of barrier contraception (ie, condoms) during the course of the study and for 3 months after discontinuation of study treatments. (For women of childbearing potential and for men who can father a child, a second method of barrier contraception in addition to condom use is recommended).
    8. Female subjects of childbearing potential must have a negative pregnancy test at screening. Females of child bearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to other causes, including prior chemotherapy, anti-estrogens, or ovarian suppression.
    Pacientes físicamente aptos con leucemia linfocítica crónica (LLC) o linfoma linfocítico de células pequeñas (LLCP), ambos sin tratamiento previo.
    1. Pacientes adultos con LLC o LLCP, definidos siguiendo los criterios del IWCLL (Hallek, 2008), sin tratamiento previo.
    2. Los pacientes deben entender y firmar voluntariamente un formulario de consentimiento informado.
    3. Los pacientes deben tener 18 años de edad o más en el momento de firmar el formulario de consentimiento informado, y deben ser capaces de ceñirse al esquema de consultas clínicas y otros requerimientos del protocolo.
    4. Los pacientes deben tener un diagnóstico documentado de LLC o LLCP [pautas del IWCLL para el diagnóstico y tratamiento de LLC (Hallek, 2008)] cumpliendo al menos uno de los siguientes criterios:
    • Evidencia de fallo medular progresivo, manifestado en el desarrollo, o empeoramiento, de anemia y/o trombocitopenia.
    • Esplenomegalia masiva (> 6 cm por debajo del margen costal izquierdo) o progresiva, o sintomática.
    • Ganglios masivos (diámetro más largo > 10 cm) o linfadenopatía progresiva o sintomática.
    • Linfocitosis progresiva con un aumento de más del 50% a lo largo de un periodo de dos meses, o un tiempo de duplicación del número de linfocitos (TDL) inferior a seis meses.
    • Al menos uno de los siguientes síntomas relacionados con la enfermedad: pérdida de peso involuntaria ≥ 10% dentro de los 6 meses previos, fatiga significativa (ECOG PS 2; no puede trabajar o es incapaz de realizar tareas habituales), fiebre superior a 38,0º C durante dos semanas o más, sin otra evidencia de infección, o sudores nocturnos durante más de un mes sin evidencia de infección.
    5. Pacientes físicamente aptos definidos como CIRS < 6.
    6. Los pacientes deben tener una puntuación del estado funcional según Grupo Cooperativo Oriental de Oncología (ECOG) igual o superior a 2.
    7. Todos los sujetos sexualmente activos (hombres o mujeres) deben emplear métodos anticonceptivos de barrera aceptados (p.ej., preservativos) durante el desarrollo del estudio y durante los tres meses posteriores a la interrupción de los tratamientos en estudio (para mujeres en edad reproductiva y hombres fértiles se recomienda un segundo método anticonceptivo de barrera además del preservativo).
    8. Las pacientes con capacidad reproductiva deben dar negativo en un test de embarazo durante el proceso de selección. Se define como mujeres con capacidad reproductiva a las mujeres sexualmente maduras que no hayan sufrido una histerectomía, o las que hayan tenido evidencia de menstruación en los 12 meses previos. Sin embargo, las mujeres con amenorrea durante 12 meses o más, aún se consideran con capacidad reproductiva si dicha amenorrea puede ser debida a otras causas, tales como quimioterapia previa, terapia con antiestrógenos o supresión ovárica.
    E.4Principal exclusion criteria
    1. Prior treatment for CLL or SLL.
    2. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form.
    3. Systemic infection that has not resolved prior to initiating study treatment in spite of adequate anti-infective therapy.
    4. Pregnant or lactating females.
    5. Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating study therapy.
    6. Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.
    7. Prior history of malignancies, other than CLL, unless the patient has been free of the disease for ≥ 3 years.
    Exceptions include the following:
    • Basal cell carcinoma of the skin
    • Squamous cell carcinoma of the skin
    • Carcinoma in situ of the cervix
    • Carcinoma in situ of the breast
    • Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
    8. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.
    9. Any of the following laboratory abnormalities:
    • Serum creatinine ≥ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft GaultAppendix C) ≤ 40 mL/min/1.73m2
    • Absolute neutrophil count (ANC) < 1.0 X 10E9/L, unless secondary to bone marrow involvement by CLL.
    • Platelet count <100,000/mm3 or <50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
    • Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetictransaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3 x upper limit of normal (ULN).
    • Serum total bilirubin > 1.5 x ULN, except in cases of Gilbert’s syndrome.
    10. Presence of autoimmune haemolytic anemia or thrombocytopenia.
    11. Disease transformation [i.e. Richter’s Syndrome (lymphomas) or prolymphocytic leukemia.
    12. Major surgery within the last 28 days prior to registration.
    13. History of stroke or intracranial haemorrhage within 6 months prior to enrolment.
    14. Currently active, clinically significant cardiovascular disease or a history of myocardial infarction within 3 months prior to enrolment.
    15. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 28 days of first dose of study drug.
    16. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
    1. Tratamiento previo para LLC o LLCP.
    2. Cualquier problema médico grave, alteración de la analítica, o una enfermedad psiquiátrica que pueda impedir que el paciente firme el formulario de consentimiento informado.
    3. Infección sistémica no resuelta antes de comenzar el tratamiento en estudio, a pesar de recibir la terapia anti infección adecuada.
    4. Mujeres embarazadas o lactantes.
    5. Haber participado en cualquier estudio clínico, o haber recibido cualquier terapia en investigación, dentro de los 28 días previos al comienzo del estudio.
    6. Infiltración del sistema nervioso central, documentada mediante una citología del fluido espinal o diagnóstico por imagen.
    7. Historia previa de neoplasias malignas, distintas de la LLC, salvo que el paciente haya estado libre de la enfermedad durante tres o más años.
    Las excepciones incluyen:
    • Carcinoma cutáneo de células basales.
    • Carcinoma cutáneo de células escamosas.
    • Carcinoma in situ de cérvix
    • Carcinoma in situ de mama
    • Hallazgo histológico incidental de cáncer de próstata (estadio TNM T1a o T1b)
    8. Infección conocida por el virus de inmunodeficiencia humana (HIV), virus de la hepatitis B (VHB) y/o virus de la hepatitis C (VHC).
    9. Cualquiera de las siguientes alteraciones analíticas:
    • Creatinina sérica ≥ 2 x LSN o tasa de filtración glomerular estimada (Cockroft Gault Apéndice C) ≤ 40 mL/min/1.73m2.
    • Recuento absoluto de neutrófilos (RAN) < 1.0 X 10E9/L, a no ser que sea secundario a la infiltración de la médula ósea por la LLC.
    • Recuento plaquetario <100.000/mm3 o <50.000/mm3 si hay afectación de la médula ósea independiente del soporte transfusional en cualquiera de las situaciones.
    • Aspartato aminotransferasa sérica (AST) / Glutámico-oxalacético transaminasa sérica (SGOT) o alanina transaminasa sérica (ALT) / glutamato piruvato transaminasa sérica (SGPT) >3 x límite superior de normalidad (LSN).
    • Bilirrubina sérica total > 1.5 x LSN, excepto en los casos de síndrome de Gilbert.
    10. Presencia de anemia hemolítica autoinmune o trombocitopenia.
    11. Transformación de la enfermedad [Síndrome de Richter (linfomas) o leucemia prolinfocítica].
    12. Cirugía mayor dentro de los 28 días previos al registro en el estudio.
    13. Historia clínica de ictus o hemorragia intracraneal dentro de los seis meses previos al reclutamiento.
    14. Enfermedad cardiovascular activa con significación clínica o historia de infarto de miocardio, dentro de los tres meses previos al reclutamiento.
    15. Requiere o recibe tratamiento anticoagulante con warfarina, o un antagonista equivalente de la vitamina K, dentro de los 28 días previos a la primera dosis del fármaco en estudio.
    16. Cualquier enfermedad potencialmente mortal, problema médico o disfunción orgánica que, en opinión del investigador, pudiera comprometer la seguridad del sujeto, interferir con la absorción o metabolización de las cápsulas de ibrutinib o exponer los resultados del estudio a un riesgo innecesario.
    E.5 End points
    E.5.1Primary end point(s)
    The primary end point is the complete response rate determined according to The IWCLL guidelines (Hallek, 2008)
    La variable principal en estudio es la tasa de respuestas completas determinada según los criterios del IWCLL (Hallek, 2008)
    E.5.1.1Timepoint(s) of evaluation of this end point
    For the primary endpoint of the study, response will be evaluated after two months of completing ofatumumab.
    Para determinar la variable principal, se evaluará la respuesta dos meses después de completar el tratamiento con ofatumumab.
    E.5.2Secondary end point(s)
    • Overall response rate, including partial response with lymphocytosis
    • Evaluation of minimal residual disease (MRD)
    • Duration of response and progression-free survival
    • Safety: type, frequency, and severity of adverse events (AEs) and relationship of AEs to ibrutinib or the combination of ibrutinib and ofatumumab
    • Response rate in relationship to molecular and genetic prognostic factors
    • Evaluate biomarkers related to BCR and compensatory signaling pathways and their association with resistance to ibrutinib treatment
    • Immunological recovery
    • Overall survival
    • Tasa global de respuesta, incluyendo la respuesta parcial con linfocitosis
    • Evaluación de la enfermedad mínima residual (EMR)
    • Duración de la respuesta y supervivencia libre de progresión
    • Seguridad: tipo, frecuencia y gravedad de los efectos adversos (EAs) y la relación de los EAs con el ibrutinib o con la combinación de ibrutinib y ofatumumab
    • Tasa de respuesta en relación con los factores pronósticos moleculares y genéticos
    • Evaluación de los biomarcadores relacionados con el BCR y con posibles vías de señalización compensatorias, y su asociación con la resistencia al tratamiento con ibrutinib
    • Recuperación inmunológica
    • Supervivencia global
    E.5.2.1Timepoint(s) of evaluation of this end point
    Response will be assessed after 12 cycles of ibrutinib to determine to continue with ibrutinib alone (patients in CR) or to consolidate the response with ofatumumab (patients not in CR). The response to therapy will be assessed after 20 cycles of treatment (2 months after completing ofatumumab) for the primary objective of the study. In addition, the best overall response will be also determined. The best overall response is defined as the best response recorded from the start of treatment until progressive disease/recurrence.
    Tras 12 meses con ibrutinib, se determinará la respuesta obtenida, para decidir si continuar sólo con ibrutinib (pacientes en RC) o realizar una consolidación con ofatumumab (pacientes que no hayan alcanzado la RC). La respuesta a la terapia se evaluará tras 20 ciclos de terapia (dos meses después de terminar el tratamiento con ofatumumab) para la variable principal del estudio. Además se determinará la mejor respuesta global, definida como la mejor respuesta obtenida desde el inicio del tratamiento hasta la progresión de la enfermedad/recurrencia.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    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.8.3 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 concerned21
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LSLV
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months60
    E.8.9.1In the Member State concerned days
    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: 42
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 42
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state84
    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)
    All patients still on study treatment at the time of cycle C42, or if the study is stopped early, will be transitioned to prescribed ibrutinib.
    Todos los pacientes que continúen con el tratamiento en estudio al final del ciclo C42, o en el caso de que el estudio se clausure prematuramente, cambiarán al tratamiento con ibrutinib prescrito.
    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 Decision2017-07-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-07-07
    P. End of Trial
    P.End of Trial StatusOngoing
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