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    Summary
    EudraCT Number:2019-000473-23
    Sponsor's Protocol Code Number:74494550AML2001
    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:2019-07-04
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2019-000473-23
    A.3Full title of the trial
    A Phase 2 Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia who are not Candidates for Intensive Chemotherapy
    Estudio fase 2 de Cusatuzumab más Azacitidina en Pacientes de Nuevo Diagnóstico de Leucemia Mieloide Aguda que no son candidatos a Quimioterapia Intensiva
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia who are not Candidates for Intensive Chemotherapy.
    Un estudio clínico de Cusatuzumab más azacitidina en pacientes con leucemia mieloide aguda recién diagnosticada que no son candidatos para quimioterapia intensiva
    A.4.1Sponsor's protocol code number74494550AML2001
    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 SponsorJanssen-Cilag International N.V.
    B.1.3.4CountryBelgium
    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 supportJanssen Research & Development, LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag, S.A.
    B.5.2Functional name of contact pointGlobal Clinical Operations Spain
    B.5.3 Address:
    B.5.3.1Street AddressAv. Paseo de las Doce Estrellas, 5-7
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28042
    B.5.3.4CountrySpain
    B.5.4Telephone number003491722 78 81
    B.5.5Fax number003491722 86 28
    B.5.6E-mailmcampagn@its.jnj.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCusatuzumab
    D.3.2Product code JNJ-74494550
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCUSATUZUMAB
    D.3.9.1CAS number 1864871-20-4
    D.3.9.2Current sponsor codeJNJ-74494550
    D.3.9.4EV Substance CodeSUB195527
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 20
    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 Vidaza
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene US, Celgene BV
    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 nameAzacitidine
    D.3.4Pharmaceutical form Powder for suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAZACITIDINE
    D.3.9.1CAS number 320-67-2
    D.3.9.4EV Substance CodeSUB05624MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Vidaza
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe B.V.
    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 nameAzacitidine
    D.3.4Pharmaceutical form Powder for 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 INNAZACITIDINE
    D.3.9.1CAS number 320-67-2
    D.3.9.4EV Substance CodeSUB05624MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.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
    Acute Myeloid Leukemia
    Leucemia mieloide aguda
    E.1.1.1Medical condition in easily understood language
    Blood cancer
    cancer en la sangre
    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 10000886
    E.1.2Term Acute myeloid 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 efficacy of cusatuzumab in combination with azacitidine in patients with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy
    Determinar la eficacia del cusatuzumab en combinación con azacitidina en pacientes con leucemia mieloide aguda (LMA) no tratada previamente que no son elegibles para la quimioterapia intensiva.
    E.2.2Secondary objectives of the trial
    1) To determine the below responses
    a) Complete response (CR)
    b) CR with incomplete recovery (CRi)
    c) CR with partial hematological revovery (CRh)
    d) CR without MRD (CRMRD-)
    e) Morphologic leukemia-free state (MLFS)
    f) Partial response (PR)
    g) Stable disease
    h) Relapse after CR, CRi, CRh
    i) Progressive Disease
    2) To assess time to response and duration of response
    3) To assess the safety profile of cusatuzumab in combination with azacitidine
    4) To assess the pharmacokinetics of cusatuzumab alone and in combination with azacitidine
    5) To assess the immunogenicity of cusatuzumab alone and in combination with azacitidine
    1) Determinar las siguientes respuestas
    a) Respuesta completa (RC)
    b) RC con recuperación incompleta (RCi)
    c) RC con recuperación hematológica parcial (RCh)
    d) RC sin MRD (RCMRD-)
    e) Estado morfológico libre de leucemia (MLFS)
    f) Respuesta parcial (RP)
    g) Enfermedad estable
    h) Recaída después de RC, RCi, RCh
    i) Enfermedad Progresiva
    2) Evaluar el tiempo de respuesta y la duración de la respuesta
    3) Evaluar el perfil de seguridad del cusatuzumab en combinación con azacitidina
    4) Evaluar la farmacocinética del cusatuzumab solo y en combinación con azacitidina.
    5) Evaluar la inmunogenicidad del cusatuzumab solo y en combinación con azacitidina.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each potential participant must satisfy all of the following criteria to be enrolled in the study:
    1. ≥18 years of age
    2. AML according to WHO 2016 criteria and fulfilling all of the following criteria that defines “not candidates for intensive chemotherapy”:
    ● ≥75 years of age or
    ● Comorbidity of at least one of the following:
    o Eastern Cooperative Oncology Group (ECOG) Performance Status of 2
    o Severe cardiac comorbidity defined as congestive heart failure or ejection fraction ≤50%
    o Severe pulmonary comorbidity defined as documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected, or forced expiratory volume in 1 second (FEV1) ≤65% of expected or dyspnea at rest requiring oxygen
    o Moderate hepatic impairment defined according to National Cancer Institute (NCI) organ dysfunction classification criteria (total bilirubin ≥1.5 up to 3 times upper lmit of normal [ULN])
    o Creatinine clearance <45 mL/ min/1.73 m² (by MDRD formula)
    o Comorbidity that, in the Investigator’s opinion, makes the patient unsuitable for intensive chemotherapy and must be documented and approved by the Sponsor before randomization
    ● De novo or secondary AML;
    ● Previously untreated AML (except: emergency leukapheresis, 1 low dose of cytarabine and/or hydroxyurea during the screening phase to control hyperleukocytosis but must be discontinued at least one day prior to start of azacitidine). All trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia is permitted but must be discontinued at least 1 day prior to the start of azacitidine;
    ● Not eligible for an allogeneic hematopoietic stem cell transplantation.
    3. ECOG Performance Status score of 0, 1 or 2.
    4. The following clinical laboratory values at screening:
    ● Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 times ULN; for participants with leukemic infiltration of the liver (documented by biopsy or imaging), AST and ALT <5 times ULN is permitted
    ● Total bilirubin ≤ 3 times ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin or in case of liver infiltration by AML (documented by biopsy or imaging) serum total bilirubin <5 times ULN
    ● Creatinine Clearance >30 mL/min (by MDRD formula)
    5. A woman must be either:
    ● Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 12 months);
    ● Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies for at least 3 months: eg, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that participant); true abstinence (when this is in line with the preferred and usual lifestyle of the participant).
    A woman of childbearing potential must have a negative highly-sensitive serum (β-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at screening.
    Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin a highly effective method of birth control, as described above.
    6. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for at least 3 months after last study treatment.
    7. Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
    Cada participante potencial debe satisfacer todos los siguientes criterios para ser reclutado en el estudio:
    1. ≥18 años de edad
    2. LMA de acuerdo con los criterios de la OMS 2016 y cumpliendo con todos los siguientes criterios que definen "no candidatos para quimioterapia intensiva":
    ● ≥75 Años de edad o
    ● Comorbilidad de al menos uno de los siguientes factores:
    estado funcional según el Eastern Cooperative Oncology Group (ECOG) de 2
    o Comorbilidad cardíaca severa definida como insuficiencia cardíaca congestiva o fracción de eyección ≤50%.
    o Comorbilidad pulmonar severa definida como enfermedad pulmonar documentada con capacidad de difusión pulmonar de monóxido de carbono (DLCO) ≤65% del volumen esperado, o volumen espiratorio forzado en 1 segundo (VEF1) ≤65% del volumen esperado o disnea en reposo que requiere oxígeno.
    o Deficiencia hepática moderada definida según los criterios de clasificación de disfunción de órganos del Instituto Nacional del Cáncer (NCI) (bilirrubina total ≥1.5 hasta 3 veces el limite superior de lo normal[ULN]).
    o Aclaramiento de creatinina <45 mL/ min/1.73 m² (por fórmula MDRD)
    o Comorbilidad que, en opinión del Investigador, hace que el paciente no sea apto para quimioterapia intensiva y debe ser documentada y aprobada por el Promotor antes de la aleatorización.
    ● AML de Novo o secundaria;
    ● LMA no tratada previamente (excepto: leucaféresis de emergencia, 1 dosis baja de citarabina y/o hidroxiurea durante la fase de detección para controlar la hiperleucocitosis, pero debe suspenderse al menos un día antes del comienzo de la azacitidina). Se permite todo tratamiento con ácido transretinoico (ATRA) para la presunta leucemia promielocítica aguda, pero debe suspenderse al menos un día antes del inicio de la azacitidina;
    ● No es elegible para un trasplante alogénico de células madre hematopoyéticas.
    3. Puntuación de estado funcional ECOG de 0, 1 ó 2.
    4. Los siguientes valores de laboratorio clínico en la seleccion:
    ● Aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) <3 veces ULN; para los pacientes con infiltración leucémica del hígado (documentada por biopsia o imágenes), se permite AST y ALT <5 veces ULN.
    ● Bilirrubina total ≤ 3 veces ULN a menos que el aumento de la bilirrubina se deba al síndrome de Gilbert o de origen no hepático o en caso de infiltración hepática por LMA (documentada mediante biopsia o imágenes) bilirrubina total en suero <5 veces ULN
    ● Depuración de creatinina >30 mL/min (por fórmula MDRD)
    5. Una mujer debe ser cualquiera de los dos:
    ● No en edad fértil: postmenopáusica (>45 años de edad con amenorrea durante al menos 12 meses);
    ● Del potencial de maternidad y la práctica de un método altamente efectivo de control de la natalidad consistente con las regulaciones locales con respecto al uso de métodos de control de la natalidad para las participantes que participan en estudios clínicos durante al menos 3 meses: por ejemplo, el uso establecido de métodos anticonceptivos hormonales orales, inyectados o implantados; la colocación de un dispositivo intrauterino (DIU) o un sistema intrauterino (SIU); los métodos de barrera: preservativo con espuma/gel/película/crema/ supositorio oclusivo (diafragma o cápsulas cervicales/bóveda) con espuma/gel/crema/supositorio espermicida; esterilización de la pareja masculina (la pareja vasectomizada debe ser la única pareja de ese participante); verdadera abstinencia (cuando esto esté en consonancia con el estilo de vida preferido y habitual del participante).
    Una mujer en edad fértil debe tener un suero negativo altamente sensible (β - gonadotropina coriónica humana[β-hCG]) o una prueba de embarazo en orina en el momento de la evaluación.
    Nota: Si el potencial de maternidad cambia después del inicio del estudio (por ejemplo, la mujer que no es heterosexualmente activa se vuelve activa, la mujer premenarcal experimenta la menarquía), la mujer debe comenzar un método altamente efectivo de control de la natalidad, como se describió anteriormente.
    6. Un hombre que es sexualmente activo con una mujer en edad fértil y no se ha sometido a una vasectomía debe estar de acuerdo en usar un método anticonceptivo de barrera, por ejemplo, ya sea un condón con espuma/gel/película/crema/supositorio espermicida o una pareja con capuchón oclusivo (diafragma o capuchón cervical/bóveda) con espuma/gel/película/crema/supositorio espermicida por lo menos durante los 3 meses posteriores al último tratamiento del estudio.
    7. Debe firmar un formulario de consentimiento informado (ICF) indicando que entiende el propósito y los procedimientos requeridos para el estudio y que está dispuesto a participar en el mismo.
    E.4Principal exclusion criteria
    Any potential participant who meets any of the following criteria will be excluded from participating in the study:
    1. Acute promyelocytic leukemia with t (15;17), or its molecular equivalent (PML-RARα).
    2. Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system.
    3. Use of immune suppressive agents for the past 4 weeks before the first administration of cusatuzumab on Cycle 1 Day 1. For regular use of systemic corticosteroids, participants may only be included if free of systemic corticosteroids for a minimum of 5 days before the first administration of cusatuzumab.
    4. Prior treatment with a hypomethylating agent for treatment of AML or MDS
    5. A diagnosis of other malignancy that requires concurrent non surgical treatment
    6. Any active untreated systemic infection
    7. A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV if tested at screening
    8. Active systemic hepatitis infection requiring treatment or other clinically active liver disease
    9. New York Heart Association Class IV heart failure or ongoing unstable angina
    10. Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (ie, mannitol, an excipient of azacitidine).
    11. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments.
    12. Major surgery, (eg, requiring general anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.
    Note: participants with planned surgical procedures to be conducted under local
    anesthesia may participate. In such cases, the investigator must notify the Sponsor before randomization.
    Cualquier participante potencial que cumpla con cualquiera de los siguientes criterios será excluido de participar en el estudio:
    1. Leucemia promielocítica aguda con t (15;17), o su equivalente molecular (PML-RARα).
    2. Afectación leucémica o síntomas clínicos de afectación leucémica del sistema nervioso central.
    3. Uso de agentes inmunosupresores durante las últimas 4 semanas antes de la primera administración de cusatuzumab en el ciclo 1 Día 1. Para el uso regular de corticosteroides sistémicos, los participantes sólo pueden ser incluidos si están libres de corticosteroides sistémicos durante un mínimo de 5 días antes de la primera administración de cusatuzumab.
    4. Tratamiento previo con un agente hipometilante para el tratamiento de la LMA o los SMD
    5. Un diagnóstico de otra neoplasia maligna que requiere tratamiento concurrente no quirúrgico
    6. Cualquier infección sistémica activa no tratada
    7. Antecedentes de anticuerpos contra el virus de la inmunodeficiencia humana (VIH) positivos o pruebas positivas para el VIH si se realizan en el momento de la prueba.
    8. Infección activa por hepatitis sistémica que requiere tratamiento u otra enfermedad hepática clínicamente activa
    9. New York Heart Association Insuficiencia cardíaca de clase IV o angina inestable continua
    10. Alergias conocidas, hipersensibilidad o intolerancia al cusatuzumab o azacitidina o sus excipientes (es decir, manitol, un excipiente de azacitidina).
    11. Cualquier condición para la cual, en la opinión del investigador, la participación no sería en el mejor interés del participante (p.e., comprometer el bienestar) o limitaciones físicas que podrían prevenir, limitar o confundir las evaluaciones especificadas en el protocolo.
    12. Cirugía mayor, (por ejemplo, que requiere anestesia general) dentro de las 4 semanas anteriores a la seleccion, o que no se haya recuperado completamente de la cirugía, o que tenga una cirugía planeada durante el tiempo que se espera que el paciente participe en el estudio.
    Nota: los participantes con procedimientos qurúrgicos planificados bajo anestesia local podrán participar. En tales casos, el investigador debe notificar al Patrocinador antes de la aleatorizacion al azar.
    E.5 End points
    E.5.1Primary end point(s)
    Complete response (CR) rate per ELN 2017 (Dohner 2017)
    Índice de respuesta completa (CR) según ELN 2017 (Dohner 2017)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Every 2 cycles (approximately every 2 months)
    Cada 2 Ciclos (aproximadamente cada 2 meses)
    E.5.2Secondary end point(s)
    1. Rate of CRh
    2. Rate of CR + CRh
    3. Rate of CRi
    4. Overall response rate (ORR) = Rate of CR+ CRh+ CRi
    5. Rate of CR without MRD
    6. Rate of MRD negativity among participants achieving CR, CRh, CRi, or MLFS ; defined as less than 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3)
    7. Time to response, defined as time from randomization to achieving the best response; duration of response, defined as time from achieving best response to disease relapse
    8. Safety profile of Adverse Events (AE) and Serious Adverse Events (SAE)
    9. Pharmacokinetics
    10. Immunogenicity / anti-drug antibody testing
    1. Tasa de RCh
    2. Tasa de RC + RCh
    3. Tasa de RCi
    4. Tasa de respuesta global (ORR) = Tasa de RC+ RCh+ RCi
    5. Tasa de RC sin MRD
    6. Tasa de negatividad de MRD entre los participantes que logran RC RCi, RCh, o MLFS; definida como menos de 1 blastos o celulas madres leucemica o leucocitos (nivel de MRD <10^-3)
    7. Tiempo de respuesta, definido como el tiempo transcurrido entre la aleatorización y haber alcanzado la mejor respuesta; duración de la respuesta, definida como el tiempo transcurrido desde haber alcanzado la mejor respuesta a la recaída de la enfermedad.
    8. Perfil de seguridad de los Eventos Adversos (EA) y de los Eventos Adversos Graves (EAG)
    9. Farmacocinética
    10. Pruebas de inmunogenicidad / anticuerpos anti Farmaco
    E.5.2.1Timepoint(s) of evaluation of this end point
    1 to 7. Every 2 cycles (approximately every 2 months)
    8. Throughout the study
    9. Cycle (C) 1 Day (D) 1, C1D3, C1D4, C1D7, C1D10, C1D17, Cycle ≥2 D3, Cycle ≥2 D17, C3D21 to C4D1, C5D21 to C6D1, and EOT (end of treatment)
    10. C1D3, C1D17, Cycle ≥2 D3, and EOT
    De 1 a 7. Cada 2 ciclos (aproximadamente cada 2 meses)
    8. A lo largo del estudio
    9. Ciclo (C) 1 día (D) 1, C1D3, C1D4, C1D7, C1D10, C1D17, Ciclo ≥2 D3, Ciclo ≥2 D17, C3D21 a C4D1, C5D21 a C6D1 y EOT (final del tratamiento)
    10. C1D3, C1D17, ciclo ≥2 D3, y EOT
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability and Biomarker evaluations
    Evaluaciones de tolerabilidad y Biomarcadores
    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 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) No
    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 EEA24
    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 Information not present in EudraCT
    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
    Brazil
    France
    Israel
    Italy
    Russian Federation
    Spain
    Switzerland
    Turkey
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study (study completion) is defined as the time at which 50% of participants have died.
    El final del estudio (finalización del estudio) se define como el momento en que el 50% de los participantes han fallecido.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    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: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 120
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 53
    F.4.2.2In the whole clinical trial 150
    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)
    Participants who are continuing to derive benefit from treatment with cusatuzumab, azacitidine or both agents as assessed by their investigator may continue to receive these medications.
    Los participantes que continúan obteniendo beneficios del tratamiento con cusatuzumab, azacitidina o ambos agentes según lo evaluado por su investigador pueden continuar recibiendo estos medicamentos.
    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 Decision2019-08-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-25
    P. End of Trial
    P.End of Trial StatusOngoing
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