Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   44208   clinical trials with a EudraCT protocol, of which   7332   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2014-005530-64
    Sponsor's Protocol Code Number:ACE-CL-006
    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:2015-08-13
    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 number2014-005530-64
    A.3Full title of the trial
    A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase 3 Study of ACP-196 Versus Ibrutinib in Previously Treated Subjects with High Risk Chronic Lymphocytic Leukemia
    Estudio de fase 3, aleatorizado, multicéntrico y abierto para evaluar la no inferioridad de ACP 196 frente a Ibrutinib en sujetos con leucemia linfocítica crónica de alto riesgo tratados previamente
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase 3 Study of ACP-196 Versus Ibrutinib in Previously Treated Subjects with High Risk Chronic Lymphocytic Leukemia
    Estudio de fase 3, aleatorizado, multicéntrico y abierto para evaluar la no inferioridad de ACP 196 frente a Ibrutinib en sujetos con leucemia linfocítica crónica de alto riesgo tratados previamente
    A.3.2Name or abbreviated title of the trial where available
    ACP-196
    ACP-196
    A.4.1Sponsor's protocol code numberACE-CL-006
    A.5.4Other Identifiers
    Name:INDNumber:118717
    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 SponsorAcerta Pharma BV
    B.1.3.4CountryNetherlands
    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 supportAcerta Pharma BV
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPPD
    B.5.2Functional name of contact pointKellie Macleod
    B.5.3 Address:
    B.5.3.1Street AddressGranta Park
    B.5.3.2Town/ cityGreatr Abingdon
    B.5.3.3Post codeCB21 6GQ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+34900834223
    B.5.6E-mailRegistroEspanolDeEstudiosClinicos@druginfo.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.3.2Product code ACP-196
    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 INNNot yet assigned
    D.3.9.2Current sponsor codeACP-196
    D.3.9.4EV Substance CodeSUB166233
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Imbruvica
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen Biotech
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1115
    D.3 Description of the IMP
    D.3.1Product nameImbruvica
    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 INNNone
    D.3.9.1CAS number 936563-96-1
    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
    High Risk Chronic Lymphocytic Leukemia
    Leucemia linfocítica crónica de alto riesgo
    E.1.1.1Medical condition in easily understood language
    Long term cancer of the blood
    Cáncer sanguíneo de largo plazo
    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 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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess whether ACP-196 is non-inferior to ibrutinib with respect to progression-free survival (PFS) based on independent review committee (IRC) assessment in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) with high-risk prognostic markers.
    Evaluar si ACP 196 es o no inferior a Ibrutinib con respecto a la supervivencia libre de progresión (SLP) según la evaluación de un comité de revisión independiente (CRI) en sujetos con leucemia linfocítica crónica (LLC) recidivante o resistente con marcadores pronósticos de alto riesgo.
    E.2.2Secondary objectives of the trial
    To evaluate the benefit:risk of ACP-196 versus ibrutinib in terms of:
    -Grade >= 3 infections
    -Richters transformation
    -Atrial fibrillation
    -Overall survival (OS)

    Safety Objectives:
    -Safety and tolerability including adverse events of interest and laboratory assessments

    Exploratory Objectives:
    -IRC-assessed overall response rate (ORR) per IWCLL 2008 criteria
    -Investigator-assessed PFS and ORR per IWCLL 2008 criteria
    -Improvement and/or resolution of disease-related symptoms
    -Improvement in incidence of diarrhea, major bleeding events, lymphocytosis, and secondary malignancy
    -Patient-reported outcome (PRO) by various scales
    -Medical resource utilization (MRU)
    -Pharmacokinetic (PK) characteristics of ACP-196 in subjects with CLL to determine which, if any, covariates (eg, age, sex, body size, race) influence exposure to ACP-196

    -Potential predictive biomarkers and mechanisms of resistance for the disease
    Evaluar la relación beneficios/riesgos de ACP 196 Vs Ibrutinib en Infecciones de grado >= 3, Transformación de Richter, Fibrilación auricular, Supervivencia global
    Objetivos de seguridad: Seguridad y tolerabilidad, incluidos acontecimientos adversos de interés y evaluaciones analíticas
    Objetivos exploratorios:TRG evaluada por el CRI conforme a los criterios IWCLL 2008.SLP y TRG evaluadas por el investigador por criterios IWCLL 2008.Mejoría o resolución de los síntomas relacionados con la enfermedad.Mejoría de la incidencia de diarrea, episodios hemorrágicos importantes,linfocitosis y neoplasias malignas secundarias.Resultados comunicados por los pacientes en distintas escalas.Uso de recursos médicos.Características farmacocinéticas de ACP-196 en los sujetos con LLC y determinación, en su caso, de las covariables (pej: edad,sexo,tamaño corporal o raza) que influyen en la exposición a ACP-196.Posibles biomarcadores predictivos y mecanismos de resistencia relacionados con la enfermedad
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Men and women >= 18 years of age.
    -Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
    -Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008):
    oMonoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing >= 1 B-cell marker (CD19, CD20, or CD23) and CD5.
    oProlymphocytes may comprise <= 55% of blood lymphocytes.
    oNo evidence of cyclin D1 rearrangement or BCL-1 over expression.
    -Must have >= 1 of the following high-risk prognostic factors:
    oPresence of 17p del by central laboratory
    oPresence of 11q del by central laboratory
    -Active disease meeting >= 1 of the following IWCLL 2008 criteria for requiring treatment:
    Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/microL).
    oMassive (ie, >= 6 cm below the left costal margin), progressive, or symptomatic splenomegaly
    oMassive nodes (ie, >= 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
    oProgressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of < 30 X 109/L (30,000/microL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
    oAutoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
    oConstitutional symptoms documented in the subjects chart with supportive objective measures, as appropriate, defined as >= 1 of the following disease-related symptoms or signs:
    Unintentional weight loss >= 10% within the previous 6 months before Screening.
    Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before Screening without evidence of infection.
    Night sweats for > 1 month before Screening without evidence of infection.
    -Measurable nodal disease by computed tomography (CT). Measurable nodal disease is defined as >= 1 lymph node > 1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.
    -Must have received >= 1 prior therapies for CLL.
    -Meet the following laboratory parameters:
    oAbsolute neutrophil count (ANC)>= 750 cells/microL (0.75 x 109/L) or >= 500 cells/microL (0.50 x 109/L) in subjects with documented bone marrow involvement and independent of growth factor support 7 days before assessment.
    oPlatelet count >= 30,000 cells/microL (30 x 109/L) without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded.
    oSerum aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) < 3.0 x upper limit of normal (ULN).
    oTotal bilirubin <= 2.5 x ULN.
    oEstimated creatinine clearance (ie, estimated glomerular filtration rate [eGFR] using Cockcroft-Gault) >= 30 mL/min.
    -Able to receive all outpatient treatment, all laboratory monitoring, and all radiologic evaluations at the institution that administers study drug for the entire study.
    -Women of childbearing potential who are sexually active with a male partner must have a negative serum pregnancy test and agree to simultaneously use 2 forms of acceptable methods of contraception (eg, condom and with either implants, injectable, oral, or intrauterine forms of contraceptives) while on the study and for 30 days after the last dose of ACP-196 or ibrutinib. Postmenopausal women (> 45 years of age and without menses for > 1 year) and surgically sterilized women are exempt from this criterion.
    -Men must agree to use acceptable methods of contraception during the study and for 30 days after the last dose of ACP-196 or ibrutinib if sexually active with a woman of childbearing potential.
    -Men must agree to refrain from sperm donation during the study and for 30 days after the last dose of ACP-196 or ibrutinib.
    -Are willing and able to adhere to the study visit schedule, understand and comply with other protocol requirements, and provide written informed consent and authorization to use protected health information. Note vulnerable subjects are not allowed on this protocol (eg, prisoners or institutionalized subjects).
    -Varones y mujeres >= 18 años.
    -Estado funcional del ECOG de 0 a 2.
    -Diagnóstico de LLC que cumpla criterios diagnósticos publicados (Hallek 2008):
    Linfocitos B monoclonales (con restricción de las cadenas ligeras kappa o lambda) con coexpresión clonal de al menos un marcador de los linfocitos B (CD19, CD20 o CD23) y CD5.
    Proporción de prolinfocitos equivalente a <= 55% de los linfocitos en sangre.
    Ausencia de datos de reordenamiento de la ciclina D1 o hiperexpresión de BCL 1.
    -Presencia de al menos uno de los siguientes factores pronósticos de alto riesgo:
    Presencia de la deleción 17p según el laboratorio central.
    Presencia de la deleción 11q según el laboratorio central.
    -Enfermedad activa que cumpla al menos uno de los siguientes criterios IWCLL 2008 de necesidad de tratamiento:
    Datos de insuficiencia medular progresiva,manifestada mediante la aparición, o el empeoramiento, de anemia (Hb<10 g/dl) o trombocitopenia (recuento de plaquetas < 100.000/µl)
    Esplenomegalia masiva (es decir, al menos 6 cm por debajo del reborde costal izquierdo), progresiva o sintomática.
    Adenopatías masivas (es decir, al menos 10 cm de diámetro mayor), progresivas o sintomáticas.
    Linfocitosis progresiva con aumento de más del 50% durante un período de dos meses o tiempo de duplicación de los linfocitos inferior a 6 meses. El TDL podrá obtenerse mediante extrapolación de regresión lineal de los recuentos absolutos de linfocitos (RAL) obtenidos a intervalos de 2 semanas durante un período de observación de 2 a 3 meses. En los sujetos con un recuento inicial de linfocitos en sangre < 30 X 109/l no podrá emplearse el TDL como único parámetro para definir la indicación de tratamiento. Además, han de descartarse factores que pudieran contribuir a la presencia de linfocitosis o adenopatías aparte de la LLC.
    Anemia o trombocitopenia autoinmunitaria con escasa respuesta al tratamiento convencional.
    Síntomas constitucionales documentados en la historia clínica del sujeto con medidas objetivas de apoyo, según proceda, definidos como uno o más de los siguientes síntomas o signos relacionados con la enfermedad:
    Pérdida de peso involuntaria >= 10% en los 6 meses previos a la selección
    Fiebre superior a 38,0 ºC durante 2 semanas o más antes de la selección sin signos de infección
    Sudores nocturnos durante más de un mes antes de la selección sin signos de infección
    -Afectación ganglionar mensurable mediante TC. Se entiende por afectación ganglionar mensurable la existencia de al menos un ganglio linfático con un diámetro > 1,5 cm en un lugar que no ha sido irradiado previamente. Una lesión irradiada solo podrá ser evaluada en cuanto a enfermedad mensurable si se ha producido progresión documentada en dicha lesión desde el final de la radioterapia
    Recepción de al menos un tratamiento previo contra la LLC
    Cumplimiento de los siguientes parámetros analíticos:
    RAN >= 750 células/µl ó >= 500 células/µl en los sujetos con afectación medular documentada e independientemente del apoyo con factores de crecimiento en los 7 días previos a la evaluación
    Recuento de plaquetas >= 30.000 células/µl sin apoyo con transfusiones en los 7 días previos a la evaluación. Quedan excluidos los sujetos con trombocitopenia dependiente de transfusiones
    AST/SGOT o ALT/SGPT en suero <= 3,0 veces el límite superior de la normalidad.
    Bilirrubina total <= 2,5 veces el LSN.
    Aclaramiento de creatinina calculado (es decir, filtración glomerular estimada [FGe] según la fórmula de Cockcroft Gault) >= 30 ml/min.
    -Voluntad y capacidad para recibir todo el tratamiento ambulatorio y de someterse a todos los controles analíticos y todas las evaluaciones radiológicas en el centro en el que se administre el fármaco del estudio durante todo el estudio.
    -Las mujeres en edad fértil que mantengan relaciones heterosexuales deberán dar negativo en una prueba de embarazo y comprometerse a utilizar simultáneamente dos métodos anticonceptivos aceptables (por ejemplo, preservativo y anticonceptivo implantable, inyectable, oral o intrauterino) durante el estudio y hasta 30 días después de la última dosis de ACP 196 o Ibrutinib. Las mujeres posmenopáusicas (mayores de 45 años y sin menstruación durante más de un año) y las esterilizadas quirúrgicamente quedan exentas de cumplir este criterio.
    -Los varones que mantengan relaciones sexuales con mujeres en edad fértil deberán comprometerse a utilizar métodos anticonceptivos aceptables durante el estudio y hasta 30 días después de la última dosis de ACP 196 o Ibrutinib.
    -Los varones deberán comprometerse a abstenerse de donar semen durante el estudio y hasta 30 días después de la última dosis de ACP 196 o Ibrutinib.
    -Voluntad y capacidad para cumplir el calendario de visitas del estudio, entender y cumplir los demás requisitos del protocolo y otorgar el consentimiento informado y la autorización para utilizar información sanitaria protegida. Hay que señalar que en este protocolo no podrán participar sujetos vulnerables
    E.4Principal exclusion criteria
    -Known central nervous system (CNS) lymphoma or leukemia.
    -Known prolymphocytic leukemia or history of, or currently suspected, Richters syndrome.
    Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone daily or equivalent).
    -Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor (eg, Bruton tyrosine kinase [Btk] inhibitors or phosphoinositide-3 [PI3] kinase inhibitors or Syk inhibitors) or a BCL-2 inhibitor (eg, ABT-199).
    -Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
    -Corticosteroid use > 20 mg within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. Subjects requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell count lowering are excluded.
    -Prior radio- or toxin-conjugated antibody therapy.
    -Prior allogeneic stem cell transplant or autologous transplant.
    -Major surgery within 4 weeks before first dose of study drug.
    -History of prior malignancy except for the following:
    oMalignancy treated with curative intent and with no evidence of active disease present for more than 3 years before Screening and felt to be at low risk for recurrence by treating physician
    oAdequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer
    oAdequately treated cervical carcinoma in situ without current evidence of disease
    -Currently active clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months before first dose with study drug.
    -Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
    -Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) or ongoing intravenous anti-infective treatment.
    -Known history of infection with human immunodeficiency virus (HIV).
    -Serologic status reflecting active hepatitis B or C infection. Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded.
    -History of stroke or intracranial hemorrhage within 6 months before randomization.
    -History of bleeding diathesis (eg, hemophilia, von Willebrand disease).
    -Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 28 days of first dose of study drug.
    -Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
    -Requires treatment with long-acting proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole)
    -Breast feeding or pregnant.
    -Concurrent participation in another therapeutic clinical trial.
    Leucemia o linfoma del sistema nervioso central conocido.
    Leucemia prolinfocítica conocida o antecedentes, o sospecha presente, de síndrome de Richter
    Anemia hemolítica autoinmunitaria o púrpura trombocitopénica idiopática no controladas, definidas como una reducción de la hemoglobina o el recuento de plaquetas secundaria a destrucción autoinmunitaria durante el período de selección o la necesidad de dosis altas de esteroides (> 20 mg al día de prednisona o equivalente)
    Exposición previa a Ibrutinib, a un inhibidor de los receptores de los linfocitos B (por ejemplo, inhibidores de la tirosina quinasa de Bruton [Btk], inhibidores de la fosfoinosítido 3 [PI3] quinasa o inhibidores de Syk) o a un inhibidor de BCL 2 (por ejemplo, ABT 199)
    Tratamiento con cualquier tipo de quimioterapia, radioterapia externa, anticuerpo contra el cáncer o fármaco experimental en los 30 días previos a la primera dosis del fármaco del estudio
    Uso de corticoides en dosis superiores a 20 mg en la semana previa a la primera dosis del fármaco del estudio, salvo los indicados por otros problemas médicos, como esteroides inhalados para tratar el asma, uso de esteroides tópicos o como premedicación antes de la administración del fármaco del estudio o de un medio de contraste. Quedan excluidos los sujetos que precisen esteroides en dosis diarias superiores a una exposición sistémica equivalente a 20 mg al día de prednisona o los que reciban esteroides para controlar la leucemia o reducir el recuento de leucocitos
    Tratamiento previo con anticuerpos conjugados con una sustancia radiactiva o toxina
    Alo o autotrasplante de células madre previo
    Intervención de cirugía mayor en las 4 semanas previas a la primera dosis del fármaco del estudio
    Antecedentes de neoplasias malignas, excepto lo siguiente:
    -Neoplasia maligna tratada con intención curativa, sin datos de enfermedad activa presente durante más de 3 años antes de la selección y que, según el médico encargado del tratamiento, tiene un riesgo bajo de recurrencia
    -Melanoma léntigo maligno debidamente tratado sin datos presentes de enfermedad o cáncer de piel distinto del melanoma debidamente controlado
    -Carcinoma in situ de cuello uterino debidamente tratado sin datos presentes de enfermedad
    Enfermedad cardiovascular de importancia clínica y activa, como arritmia no controlada o sintomática, insuficiencia cardíaca congestiva, cualquier cardiopatía en clase 3 o 4 conforme a la clasificación funcional de la New York Heart Association o antecedentes de infarto de miocardio en los 6 meses previos a la primera dosis del fármaco del estudio
    Incapacidad de tragar cápsulas, síndrome de malabsorción, enfermedad con afectación significativa de la función gastrointestinal, resección del estómago o intestino delgado, derivación gástrica, enfermedad intestinal inflamatoria sintomática u obstrucción intestinal parcial o completa
    Infección micótica, bacteriana, viral o de otro tipo sistémica, activa y no controlada (definida como la presencia de signos y síntomas persistentes relacionados con la infección sin mejoría a pesar de recibir un tratamiento apropiado con antibióticos u otros tratamientos) o tratamiento antiinfeccioso por vía intravenosa en curso
    Antecedentes de infección por el VIH
    Estado serológico indicativo de una infección activa por el virus de la hepatitis B o C. Los sujetos con resultados positivos para anticuerpos contra el antígeno nuclear del virus de la hepatitis B y negativos para el antígeno de superficie o con resultados positivos para anticuerpos contra el virus de la hepatitis C deberán tener un resultado negativo en una reacción en cadena de la polimerasa antes de su inclusión. Quedan excluidos los que den positivo para el antígeno de superficie del virus de la hepatitis B, así como aquellos con resultados positivos en la PCR para virus de la hepatitis B o virus de la hepatitis C
    Antecedentes de ictus o hemorragia intracraneal en los 6 meses previos a la aleatorización
    Antecedentes de diátesis hemorrágica (por ejemplo, hemofilia, enfermedad de von Willebrand)
    Necesidad o recepción de tratamiento anticoagulante con warfarina o un antagonista de la vitamina K equivalente (por ejemplo, fenprocumón) en los 28 días previos a la primera dosis del fármaco del estudio
    Necesidad de tratamiento con un inhibidor o inductor potente de la enzima 3A4 del citocromo P450 (CYP3A4).
    Necesidad de tratamiento con inhibidores de la bomba de protones de acción prolongada (por ejemplo, omeprazol, esomeprazol, lansoprazol, dexlansoprazol, rabeprazol o pantoprazol)
    Mujeres embarazadas o en período de lactancia
    Participación simultánea en otro ensayo clínico terapéutico
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the study is progression-free survival (PFS). The primary hypothesis is ACP-196 is non-inferior to ibrutinib with respect to PFS as assessed by IRC review per IWCLL 2008 criteria.
    El criterio de valoración principal de este estudio es la SLP. La hipótesis principal es que ACP 196 no es inferior a Ibrutinib con respecto a la SLP según la evaluación del CRI conforme a los criterios IWCLL 2008.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint of the study is progression-free survival (PFS). The primary hypothesis is ACP-196 is non-inferior to ibrutinib with respect to PFS as assessed by IRC review per IWCLL 2008 criteria. 48 months - estimated
    El criterio de valoración principal de este estudio es la SLP. La hipótesis principal es que ACP 196 no es inferior a Ibrutinib con respecto a la SLP según la evaluación del CRI conforme a los criterios IWCLL 2008. Estimado en 48 meses.
    E.5.2Secondary end point(s)
    To compare between ACP-196 and ibrutinib in terms of:
    -Incidence of Grade >= 3 infections
    -Incidence of Richter?s transformation
    -Incidence of atrial fibrillation
    -OS
    Comparar ACP 196 e Ibrutinib en cuanto a:
    -Incidencia de infecciones de grado >= 3.
    -Incidencia de transformación de Richter.
    -Incidencia de fibrilación auricular.
    -SG.
    E.5.2.1Timepoint(s) of evaluation of this end point
    estimated 48 months
    Estimado en 48 meses.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic 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 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group 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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA35
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    France
    Germany
    Israel
    Italy
    Netherlands
    New Zealand
    Poland
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    UVUP
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 400
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 500
    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)
    Treatment to continue as per normal treatment for this condition.
    Se continuará con el tratamiento habitual para esta condición
    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 Decision2015-07-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-07-13
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA