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    Summary
    EudraCT Number:2019-003576-40
    Sponsor's Protocol Code Number:74494550MDS2001
    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:2020-01-23
    Trial results View 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 number2019-003576-40
    A.3Full title of the trial
    A Phase 2, Randomized, Open-label Study of Cusatuzumab in Combination with Azacitidine Compared with Azacitidine Alone in Patients with Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and who are not candidates for Hematopoietic Stem Cell Transplantation (HSCT)
    Estudio fase II, aleatorizado y abierto de cusatuzumab en combinacion con azacitdina comparados con azacitidina en monoterapia en pacientes con sindrome sindrome mielodisplasico (SMD) o leucemia mielomonocitica cronica (LMMC) de alto riesgo que no son candidatos para un trasplante de celulas madre hematopoyeticas (TCMH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical Study of Cusatuzumab in Combination with Azacitidine Compared with Azacitidine Alone in Patients with Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and who are not candidates for Hematopoietic Stem Cell Transplantation (HSCT)
    Un estudio clinico de Cusatuzumab en combinacion con azacitidina comparado con azacitidina sola en pacientes con sindrome mielodisplasico (SMD) o leucemia mielomonocitica cronica (LMMC) de alto riesgo y que no son candidatos para el traasplante de celulas madre hematopoyeticas (TCMH)
    A.4.1Sponsor's protocol code number74494550MDS2001
    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 number+34917227881
    B.5.5Fax number+34917228628
    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/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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.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
    Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
    Síndrome mielodisplásico (SMD) o leucemia mielomonocítica crónica (LMMC)
    E.1.1.1Medical condition in easily understood language
    Blood Cancer
    Cáncer de Sangre
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10028533
    E.1.2Term Myelodysplastic syndrome
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10054350
    E.1.2Term Chronic myelomonocytic leukemia
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare overall response rate (ORR) between treatment groups in subjects with higher-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who are not eligible for hematopoietic stem cell transplantation (HSCT)
    Comparar la tasa de respuesta global (ORR) entre los grupos de tratamiento en pacientes con síndrome mielodisplásico (SMD) o leucemia mielomonocítica crónica (LMMC) de alto riesgo que no son elegibles para trasplante de células madre hematopoyéticas (TCMH).
    E.2.2Secondary objectives of the trial
    1. To compare the following between treatment groups:
    • Proportion of subjects achieving complete remission (CR)+partial remission (PR)
    • Proportion of subjects achieving CR
    • Time to response
    • Duration of response
    • Transfusion (red blood cell [RBC] or platelets) independence
    • Transformation to acute myeloid leukemia (AML) according to World Health Organization (WHO) criteria
    • Progression-free survival (PFS)
    • Overall survival (OS)
    • Hematologic improvement
    2. To assess the safety profile of cusatuzumab in combination with azacitidine
    3. To assess changes in physical function/symptoms
    4. To assess the pharmacokinetics (PK) of cusatuzumab in combination with azacitidine
    5. To assess the immunogenicity of cusatuzumab
    1. Comparar lo siguiente entre los grupos de tratamiento:
    - Proporción de pacientes que lograron la remisión completa (RC) + remisión parcial (RP)
    - Proporción de pacientes que logran la RC
    - Tiempo de respuesta
    - Duración de la respuesta
    - Independencia de la transfusión (glóbulos rojos[RBC] o plaquetas)
    - Transformación a leucemia mieloide aguda (LMA) según los criterios de la Organización Mundial de la Salud (OMS)
    - Supervivencia libre de progresión (PFS)
    - Supervivencia global (SG)
    - Mejoramiento hematológico
    2. Evaluar el perfil de seguridad de custuzumab en combinacion con azacitidina
    3. Evaluar los cambios en las funciones/sintomas fisicos.
    4. Evaluar la farmacocinetca (PK) de cusatuzumab en combinacion con azacitidina
    5. Evaluar la inmunogenecidad de cusatuzumab.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each potential subject must satisfy all of the following criteria to be randomized in the study:
    1. Age ≥18 years.
    2. Diagnosis of de novo or secondary higher-risk MDS or CMML per WHO 2016 criteria.
    3. At study entry, higher-risk MDS (intermediate, high, and very high risk MDS per IPSS-R) OR higher-risk CMML (intermediate-2 or high risk CMML per CPSS-Mol). Appendix 5 of the protocol presents the relevant prognostic tools. Subjects with previous lower-risk MDS or CMML that has evolved to higher-risk MDS or CMML are eligible.
    4. At study entry, not a candidate for HSCT.
    5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
    6. Adequate liver and renal function defined as follows:
    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3× upper limit of normal (ULN)
    • Total bilirubin ≤1.5×ULN, unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
    • Creatinine clearance (CrCl) >30 mL/min/1.73 m² (by Modification of Diet in Renal Disease formula).
    7. A woman of childbearing potential must have a negative highly-sensitive serum (β-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at screening.
    8. Women of childbearing potential (defined as: fertile, following menarche and until becoming postmenopausal unless permanently sterile):
    a. Must be practicing a highly-effective method of birth control (failure rate of <1% per year when used consistently and correctly) during treatment and for 3 months after the last dose of study drug. Examples of highly effective methods of contraception are located in Appendix 6 of the protocol.
    b. Must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during treatment and for 3 months after the last dose of study drug.
    c. Must not be breastfeeding and not planning to become pregnant during treatment and for 3 months after the last dose of study drug.
    9. Men who are sexually active with women of childbearing potential and have not had a vasectomy, must:
    a. 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) during treatment and for 3 months after the last dose of study drug
    b. Agree to not donate sperm during treatment and for 3 months after the last dose of study drug
    c. Not plan to father a child during treatment or within 3 months after the last dose of study drug
    10. The potential subject or a legally authorized representative 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.
    Cada paciente potencial debe satisfacer todos los siguientes criterios para ser incluido en el estudio:
    1. Edad ≥18 años.
    2. Diagnostico de MDS o CMML de alto riesgo de novo o secundario segundo los criterios de la OMS 2016.
    3. Al inicio del estudio, MDS de riesgo alto(MDS de riesgo intermedio, alto y muy alto según IPSS-R) O CMML de riesgo alto (CMML de riesgo intermedio-2 o alto según CPSS-Mol). El anexo 5 del protocolo presenta las herramientas de pronóstico pertinentes. Los pacientes con MDS o CMML previos de bajo riesgo que han evolucionado a MDS o CMML de riesgo alto son elegibles.
    4. En el momento de ingresar al estudio, no es un candidato para TCMH.
    5. Puntuación del estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0, 1 ó 2
    6. Función hepática y renal adecuada definida como:
    - Aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) <3× límite superior de lo normal (ULN)
    - Bilirrubina total ≤1.5×ULN, a menos que el aumento de la bilirrubina se deba al síndrome de Gilbert o de origen no hepático.
    - Aclaramiento de creatinina (CrCl) >30 mL/min/1.73 m² (mediante la modificación de la fórmula Diet in Renal Disease).
    7. 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 durante el periodo de seleccion.
    8. Mujeres con potencial para procrear (definidas como: fértiles, después de la menarquia y hasta llegar a ser postmenopáusicas, a menos que sean permanentemente estériles):
    a. Deben estar practicando un método altamente efectivo de control de la natalidad (tasa de fracaso de <1% por año cuando se usa consistente y correctamente) durante el tratamiento y durante 3 meses después de la última dosis del medicamento en estudio. En el Apéndice 6 del protocolo se presentan ejemplos de métodos anticonceptivos altamente eficaces.
    b. Deben aceptar no donar óvulos (óvulos, ovocitos) para fines de reproducción asistida durante el tratamiento y durante los 3 meses posteriores a la última dosis del medicamento en estudio.
    c. No debe estar amamantando y no planear quedar embarazada durante el tratamiento y durante 3 meses después de la última dosis del medicamento en estudio.
    9. Los hombres que son sexualmente activos con mujeres en edad fértil y que no se han sometido a una vasectomía, deben:
    a. Aceptar el uso de un método anticonceptivo de barrera (p. ej., condón con espuma/gel/película/crema/supositorio espermicida o pareja con capuchón oclusivo[diafragma o capuchón cervical/bóveda] con espuma/gel/película/crema/supositorio espermicida) durante el tratamiento y durante 3 meses después de la última dosis del fármaco del estudio.
    b. Aceptar no donar esperma durante el tratamiento y durante 3 meses después de la última dosis del medicamento en estudio.
    c. No planear engendrar un hijo durante el tratamiento o dentro de los 3 meses después de la última dosis del medicamento en estudio.
    10. El posible paciente o un representante legalmente autorizado debe firmar un documento de consentimiento informado (ICF) indicando que entiende el propósito y los procedimientos requeridos para el estudio y que está dispuesto a participar.
    E.4Principal exclusion criteria
    Any potential subject who meets any of the following criteria will be excluded from participating in the study:
    1. Received prior HSCT or any prior treatment, including HMAs, for higher-risk MDS or CMML. Prior supportive therapies including transfusion and growth factors are acceptable.
    2. Received prior treatment with cusatuzumab.
    3. Presence of any of the following genetic abnormalities regardless of blast count:
    a. t(8;21)(q22;q22); RUNX1-RUNX1T1 (previously AML1-ETO)
    b. inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
    c. t(15;17)(q22;q21.1); PML-RARA
    4. Presence of the bcr-abl rearrangement (ie, Philadelphia chromosome).
    5. Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug.
    6. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
    a. Non-muscle invasive bladder cancer
    b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured
    c. Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.
    d. Localized prostate cancer (N0M0):
    • With a Gleason score of 6, treated within the last 24 months or untreated and under surveillance
    • With a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence
    • Or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy and considered to have a very low risk of recurrence
    e. Breast cancer:
    • Adequately treated lobular carcinoma in situ or ductal carcinoma in situ
    • Or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence
    f. Malignancy that is considered cured with minimal risk of recurrence.
    7. Any active systemic infection.
    8. History of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV at screening.
    9. Known hepatitis C infection or positive serologic testing for hepatitis C (anti-hepatitis C virus antibody).
    10. Seropositive for hepatitis B, defined by a positive test for hepatitis B surface antigen [HBsAg]. Subjects with resolved infection (ie, subjects who are HBsAg negative with antibodies to total hepatitis B core antigen [anti-HBc] with or without the presence of hepatitis B surface antibody [anti-HBs]) must be screened using real-time polymerase chain reaction (RT-PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are RT-PCR positive will be excluded. Subjects with serologic findings suggestive of HBV vaccination (ie, anti-HBs positivity as the only serologic marker) and a known history of prior HBV vaccination do not need to be tested for HBV DNA by RT-PCR.
    11. New York Heart Association Class 4 heart failure or ongoing unstable angina.
    12. Known allergies, hypersensitivity, or intolerance to cusatuzumab, azacitidine, or their excipients (eg, mannitol, an excipient of azacitidine).
    13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments.
    14. Major surgery (eg, requiring general anesthesia) within 4 weeks prior to initiation of study treatment.
    Cualquier paciente potencial que cumpla con cualquiera de los siguientes criterios será excluido de participar en el estudio:
    1. Recibió antes TCMH o cualquier tratamiento previo, incluyendo HMAs, para MDS o CMML de alto riesgo. Las terapias de apoyo previas, incluyendo transfusiones y factores de crecimiento, son aceptables.
    2. Recibió tratamiento previo con cusatuzumab.
    3. Presencia de cualquiera de las siguientes anomalías genéticas, independientemente del número de blastos:
    a. t(8;21)(q22;q22); RUNX1-RUNX1T1 (anteriormente AML1-ETO)
    b. inv(16)(p13.1q22) o t(16;16)(p13.1;q22); CBFB-MYH11
    c. t(15;17)(q22;q21.1); PML-RARA
    4. Presencia del reordenamiento bcr-abl (es decir, el cromosoma Filadelfia).
    5. Recibió una vacuna viva atenuada dentro de las 4 semanas anteriores al inicio del medicamento en estudio.
    6. Malignidades activas (es decir, que progresan o requieren cambio de tratamiento en los últimos 24 meses) que no sean la enfermedad que se está tratando en estudio. Las únicas excepciones permitidas son:
    a. Cáncer de vejiga que no haya invadido el musculo.
    b. Cáncer de piel (no melanoma o melanoma) tratado en los últimos 24 meses que se considera completamente curado
    c. Cáncer de cuello uterino no invasivo tratado en los últimos 24 meses que se considera completamente curado.
    d. Cáncer de próstata localizado (N0M0):
    - Con un puntaje de Gleason de 6, tratados en los últimos 24 meses o no tratados y bajo vigilancia
    - Con una puntuación de Gleason de 3+4 que ha sido tratada más de 6 meses antes de la seleccion completa del estudio y se considera que tiene un riesgo muy bajo de recurrencia.
    - O antecedentes de cáncer de próstata localizado (N0M0) y de recibir terapia de privación de andrógenos y se considera que tienen un riesgo muy bajo de recurrencia.
    e. Cáncer de mama:
    - Carcinoma lobullilar in situ o carcinoma ductal in situ tratados adecuadamente.
    - O antecedentes de cáncer de mama localizado y de recibir agentes antihormonales y se considera que tienen un riesgo muy bajo de recurrencia.
    f. Malignidad que se considera curada con un riesgo mínimo de recurrencia.
    7. Cualquier infección sistémica activa.
    8. Antecedentes de anticuerpos contra el virus de inmunodeficiencia humana (VIH) positivos o pruebas positivas para el VIH durante la selección.
    9. Infección conocida de hepatitis C o pruebas serológicas positivas para hepatitis C (anticuerpos contra el virus de la hepatitis C).
    10. Seropositivo para hepatitis B, definido por una prueba positiva para el antígeno de superficie de la hepatitis B[HBsAg]. Los pacientes con infección resuelta (es decir, los pacientes que son negativos al HBsAg con anticuerpos contra el antígeno del core de la hepatitis B total[anti-HBc] con o sin la presencia de anticuerpos de superficie de la hepatitis B[anti-HBBs]) deben ser examinados utilizando la medición en tiempo real de los niveles de ADN del virus de la hepatitis B (VHB) por reacción en cadena de la polimerasa (RT-PCR). Se excluirá a los que sean positivos a la RT-PCR. Los pacientes con hallazgos serológicos que sugieran la vacunación contra el VHB (es decir, la positividad frente al VHB como único marcador serológico) y un historial conocido de vacunación previa contra el VHB no necesitan ser sometidos a pruebas de ADN del VHB mediante RT-PCR.
    11. insuficienca cardiaca de clase 4 segun la Asociacion Cardiaca de Nueva York (New York Heart Association) o angina inestable en curso.
    12. Alergias conocidas, hipersensibilidad o intolerancia al cusatuzumab, azacitidina o sus excipientes (p. ej., manitol, un excipiente de azacitidina).
    13. Cualquier condición para la cual, en la opinión del investigador, la participación no sería en el mejor interés del paciente (p.e., comprometer el bienestar) o limitaciones físicas que podrían prevenir, limitar o confundir los procedimientos especificos del ensayo.
    14. Cirugias mayores (por ejemplo que requieran anestesia general) en las 4 semansa anteriores al incio del tratamiento del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Overall response rate (ORR) (rate of Complete remission [CR] + partial remission [PR] + marrow complete remission [mCR]), per modified International Working Group (IWG) criteria
    Tasa de respuesta global (ORR) (tasa de remisión completa[RC] + remisión parcial[RP] + remisión completa de la médula ósea[mRC]), según los criterios modificados del Grupo Internacional de Trabajo (GIT).
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Within 14 days of Cycle (C)1 Day (D)1; Cycles 4, 8, and 12, then every 6 cycles until disease relapse from CR, PR, or mCR; progression; or transformation to AML or death, End of treatment
    1. Dentro de los 14 días del Ciclo (C)1 Día (D)1; Ciclos 4, 8, y 12, luego cada 6 ciclos hasta que la enfermedad recaiga por RC, RP, o mRC; progresión; o transformación a LMA o muerte, Fin del tratamiento.
    E.5.2Secondary end point(s)
    1. a) CR + PR rate, per modified IWG criteria
    b) CR rate, per modified IWG criteria
    c) Time to response for subjects who achieved such responses, defined as time from randomization to achieving the first response of CR, PR, or mCR, per modified IWG criteria
    d) Time from achieving the first response of CR, PR, or mCR to relapse or death from any cause for those subjects who responded
    e) Transfusion independence, defined as a period of ≥56 consecutive days with no transfusion occurring between the first and last dose of study drug +30 days
    f) Transformation to AML, defined as ≥20% bone marrow blasts
    g) Progression-free survival (PFS), defined as the time from randomization to disease progression; relapse from CR, PR, or mCR; or death from any cause
    h) OS, defined as the time from randomization to death
    i) Hematologic improvement rate, per modified IWG criteria
    2. Safety parameters, including AEs and laboratory tests
    3. Proportion of subjects achieving a clinically meaningful improvement in Functional Assessment of Cancer Therapy-Anemia -Trial Outcome Index (FACT-An TOI)
    4. Serum concentration-time profile and PK parameters for cusatuzumab
    5. Characterization and quantification of anti-drug antibodies (ADAs)
    1. a) Tasa de RC + RP, por criterios GIT modificados
    b) Tasa de RC, según criterios GIT modificados
    c) Tiempo de respuesta para los pacientes que lograron dichas respuestas, definido como el tiempo transcurrido desde la aleatorización hasta la obtención de la primera respuesta de RC, RP o mRC, según los criterios modificados del GIT.
    d) Tiempo desde que se obtiene la primera respuesta del RC, RP o mRC hasta la recaída o muerte por cualquier causa de los pacientes que respondieron.
    e) Independencia de la transfusión, definida como un período de ≥56 días consecutivos sin que se produzca ninguna transfusión entre la primera y la última dosis del fármaco en estudio +30 días.
    f) Transformación a LMA, definida como ≥20% de blastos de médula ósea
    g) Supervivencia libre de progresión (SLP), definida como el tiempo transcurrido desde la aleatorización hasta la progresión de la enfermedad; recaída de la RC, RP o mRC; o muerte por cualquier causa.
    h) SG, definida como el tiempo transcurrido desde la aleatorización hasta la muerte
    i) Tasa de mejora hematológica, según criterios modificados del GIT
    2. Parámetros de seguridad, incluidos los EA y las pruebas de laboratorio
    3. Proporción de pacientes que logran una mejora clínicamente significativa en la Evaluación Funcional de la Terapia del Cáncer - Anemia - Índice de Resultados de Ensayos (FACT-An TOI)
    4. Perfil concentración-tiempo en suero y parámetros PK para cusatuzumab
    5. Caracterización y cuantificación de anticuerpos antifarmaco (ADAs)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Within 14 days of Cycle (C)1 Day (D)1; Cycles 4, 8, and 12, then every 6 cycles until relapse or disease progression; or transformation to AML or death, End of treatment
    2. Screening Day 1 of each 28 day cycle until 30 days after end of treatment or death
    3. C1D1; Cycles 4, 8 and 12, then every 6 cycles until relapse or disease progression, transformation to AML or death; End of treatment
    4. Screening, Cycle 1: Day 3, Day 4 and Day 17, C2D3, C3D3, C4D3, C4D21 to Cycle 5 Day 1 at disease evaluation, C8D3, C11D3, and End of treatment
    5. C1D3, C1D17, C2D3, C3D3, C4D3, C8D3, C11D3, and End of treatment
    1. Dentro de los 14 días del Ciclo (C)1 Día (D)1; Ciclos 4, 8 y 12, luego cada 6 ciclos hasta la recaída o progresión de la enfermedad; o transformación a LMA o muerte, Fin del tratamiento.
    2. Selección día 1 de cada ciclo de 28 días hasta 30 días después del final del tratamiento o de la muerte
    3. C1D1; Ciclos 4, 8 y 12, luego cada 6 ciclos hasta la recaída o progresión de la enfermedad, transformación a LMA o muerte; Fin del tratamiento.
    4. Selección, Ciclo 1: Día 3, Día 4 y Día 17, C2D3, C3D3, C4D3, C4D21 al Ciclo 5 Día 1 en la evaluación de la enfermedad, C8D3, C11D3, y Fin del tratamiento
    5. C1D3, C1D17, C2D3, C3D3, C4D3, C8D3, C11D3 y Fin del tratamiento
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic 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
    Immunogenicity, Biomarker Evaluation, Patient-Reported Outcomes (PRO) Evaluation, Medical Resource Utilization Evaluation and Receptor Occupancy
    Inmunogenicidad, Evaluación de Biomarcadores, Evaluación de Resultados Reportados por el Paciente (PRO), Evaluación de Utilización de Recursos Médicos y Ocupación del Receptor
    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 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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA42
    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
    Brazil
    Czech Republic
    France
    Germany
    Italy
    Japan
    Russian Federation
    Saudi Arabia
    Spain
    Switzerland
    Turkey
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study (study completion) is defined as the time at which 50% of subjects have died or when the Sponsor decides to stop the study, whichever occurs first. The Sponsor will ensure that subjects benefiting from study treatment will be able to continue receiving study therapy.
    El final del estudio (finalización del estudio) se define como el momento en que el 50% de los sujetos han fallecido o cuando el Patrocinador decide interrumpir el estudio, lo que ocurra primero. El Patrocinador se asegurará de que los sujetos que se benefician del tratamiento del estudio puedan continuar recibiendo la terapia del estudio.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days13
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days13
    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: 60
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 90
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Refer to protocol and informed consent form.
    Consulte el protocolo y el formulario de consentimiento informado.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state17
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 66
    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)
    The Sponsor will ensure that subjects benefiting from study treatment will be able to continue receiving study therapy.
    El Promotor se asegurará de que los sujetos que se benefician del tratamiento del estudio puedan continuar recibiendo la terapia del estudio.
    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 Decision2020-03-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-02-25
    P. End of Trial
    P.End of Trial StatusOngoing
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