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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39572   clinical trials with a EudraCT protocol, of which   6487   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).
     
    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:2019-002477-56
    Sponsor's Protocol Code Number:IMGN632-0802
    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:2019-10-21
    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 number2019-002477-56
    A.3Full title of the trial
    A Phase 1b/2 Study of IMGN632 as Monotherapy or Combination with Venetoclax and/or Azacitidine for Patients with CD123-Positive Acute Myeloid Leukemia
    Estudio de fase 1b/2 de IMGN632 como monoterapia o en combinación con venetoclax y/o azacitidina en pacientes con leucemia mieloide aguda con valor positivo de CD123
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of IMGN632 alone or in combination with Venetoclax and/or Azacitidine for Patients with CD123-Positive Acute Myeloid Leukemia
    Estudio de IMGN632 solo o en combinación con venetoclax y/o azacitidina para pacientes con leucemia mieloide aguda positiva a CD123
    A.4.1Sponsor's protocol code numberIMGN632-0802
    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 SponsorImmunoGen, Inc.
    B.1.3.4CountryUnited States
    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 supportImmunoGen, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationImmunoGen, Inc.
    B.5.2Functional name of contact pointKen Dhimitri
    B.5.3 Address:
    B.5.3.1Street Address830 Winter Street
    B.5.3.2Town/ cityWaltham
    B.5.3.3Post code02451
    B.5.3.4CountryUnited States
    B.5.4Telephone number001781895-0600
    B.5.5Fax number001781207-5341
    B.5.6E-mailIMGN0802@immunogen.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 nameIMGN632
    D.3.2Product code IMGN632
    D.3.4Pharmaceutical form Powder 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 INNIMGN632
    D.3.9.2Current sponsor codeIMGN632
    D.3.9.3Other descriptive nameG4723A-DGN549-C
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 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 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 nameVidaza
    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 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 Venclyxto
    D.2.1.1.2Name of the Marketing Authorisation holderAbbVie Deustchland GmbH & Co. KG
    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 nameVenclyxto
    D.3.4Pharmaceutical form Tablet
    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 INNVENETOCLAX
    D.3.9.1CAS number 1257044-40-8
    D.3.9.4EV Substance CodeSUB176260
    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.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
    CD123 positive Acute Myeloid Leukemia
    leucemia mieloide aguda con valor positivo de CD123
    E.1.1.1Medical condition in easily understood language
    Acute Myeloid Leukemia
    leucemia mieloide aguda
    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 SOC
    E.1.2Classification code 10029104
    E.1.2Term Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. Dose Escalation Cohorts:
    Evaluate the safety and tolerability and identify an RP2D of IMGN632 when administered in combination with azacitidine (Regimen A), venetoclax (Regimen B), azacitidine+venetoclax (Regimen C) in patients with relapsed AML.

    2. Dose Expansion Cohorts:
    a. Assess preliminary antileukemia activity of IMGN632 when administered in combination with azacitidine (Regimen A), venetoclax (Regimen B), azacitidine+venetoclax (Regimen C) in patients with either relapsed or untreated AML and assess MRD levels.
    b. Regimen D (IMGN632 monotherapy in MRD + maintenance): Assess preliminary antileukemia activity of IMGN632 when administered as monotherapy in patients with MRD + AML after frontline therapy
    1. Cohortes de aumento escalonado de la dosis:
    Evaluar la seguridad y tolerabilidad e identificar una RP2D) del IMGN632 cuando se lo administra en combinación con azacitidina (Régimen A), venetoclax (Régimen B), azacitidina + venetoclax (Régimen C) en pacientes con LMA recidivante

    2. Cohortes de expansión de la dosis
    a. Evaluar la actividad preliminar contra la leucemia del IMGN632 cuando se lo administra en combinación con azacitidina (Régimen A), venetoclax (Régimen B), azacitidina + venetoclax (Régimen C) en pacientes con LMA recidivante o sin tratamiento previo y evaluar los niveles de MRD
    b. Régimen D (IMGN632 como monoterapia de mantenimiento para ERM+): Evaluar la actividad preliminar contra la leucemia del IMGN632 cuando se lo administra como monoterapia a pacientes con LMA con ERM+ después de la primera línea de tratamiento
    E.2.2Secondary objectives of the trial
    Dose Escalation Cohorts (Regimen A, B and C)
    1. Evaluate the safety and tolerability of IMGN632 when administered in combination with azacitidine (Regimen A), venetoclax (Regimen B), azacitidine + venetoclax (Regimen C) in patients with AML
    2. Characterize the PK of IMGN632 in combination with azacitidine (Regimen A), venetoclax (Regimen B), azacitidine + venetoclax (Regimen C)
    3. Evaluate azacitidine, venetoclax and azacitidine + venetoclax concentrations when administered in combination with IMGN632
    4. Characterize the immunogenicity of IMGN632
    5. Assess MRD levels during the Escalation Phase

    Dose Expansion Cohort: Regimen D (IMGN632 monotherapy in MRD+ maintenance)
    1. Evaluate the safety and tolerability of IMGN632 when administered as monotherapy in patients with MRD + AML
    2. Characterize the PK of IMGN632
    3. Characterize the immunogenicity of IMGN632
    Cohortes de aumento escalonado de la dosis (Régimen A, B y C):
    1. Evaluar la seguridad y tolerabilidad del IMGN632 cuando se lo administra en combinación con azacitidina (Régimen A), venetoclax (Régimen B), azacitidina + venetoclax (Régimen C) en pacientes con LMA
    2. Caracterizar la farmacocinética del IMGN632 en combinación con azacitidina (Régimen A), venetoclax (Régimen B), azacitidina + venetoclax (Régimen C)
    3. Evaluar las concentraciones de la azacitidina, venetoclax y azacitidina + venetoclax cuando se la administra en combinación con el IMGN632
    4. Caracterizar la inmunogenia del IMGN632
    5. Evaluar los niveles de ERM durante la fase de aumento escalonado de la dosis
    Cohortes de expansión de la dosis: Régimen D (IMGN632 como monoterapia de mantenimiento para ERM+)
    1. Evaluar la seguridad y tolerabilidad del IMGN632 cuando se lo administra como monoterapia a pacientes con LMA con ERM+
    2. Caracterizar la PK del IMGN632
    3. Caracterizar la inmunogenia del IMGN632
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patient must be ≥ 18 years of age.
    2. Patients must have confirmed diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization classification.
    3. Disease characteristics and allowable prior therapy:
    a. Patients must be evaluated for any available standard of care therapies and, in the opinion of the treating physician, be deemed appropriate for this experimental therapy.
    b. Treatment-naïve (untreated) patients will be allowed in the Expansion Phase for Regimens A (IMGN632 + azacitidine) and C (IMGN632 + azacitidine + venetoclax). No prior treatments with HMAs for MDS are allowed.
    c. Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry [IHC]).
    d. Patients may have received prior CD123-targeted therapies, except IMGN632, as long as CD123 remains detectable during screening.
    e. Relapsed AML patients will be allowed to enroll in the Escalation Phase of Regimens A, B, and C (IMGN632 + azacitidine, venetoclax, or azacitidine + venetoclax, respectively) and the Expansion Phase of Regimens A and B and may have received up to 2 prior lines of therapy, eg, frontline treatment (induction, consolidation [including transplant], and maintenance) and 1 salvage regimen.
    f. Patients enrolling in Regimen D must be in CR (CR/CRi) for no more than 6 months and be MRD+, confirmed by central laboratory testing, after intensive induction/consolidation therapy.
    4. Patients enrolling on Regimen D (MRD+ AML), must first have an evaluable screening bone marrow sample confirmed as MRD+ by central flow testing of MRD.
    5. Eastern Cooperative Oncology Group performance status ≤ 1. If nonambulatory due to a chronic disability, must be Karnofsky performance status > 70.
    6. Previous treatment-related toxicities must have resolved to Grade 1 or baseline (excluding alopecia).
    7. Total white blood cell count must be less than 25 x 10e9 cells/L. Hydroxyurea may be used to control blood counts before Cycle 1 Day 1, at the discretion of the treating physician, according to institutional practice. During the Escalation Phase in Regimens A-C, hydroxyurea may also be used during Cycle 1.
    8. Liver enzymes (AST and ALT) ≤ 3 × the upper limit of normal (ULN).
    9. Total bilirubin ≤ 1.5 × the ULN within 14 days of enrollment.
    10. Serum creatinine ≤ 1.5 mg/dL within 14 days of enrollment.
    11. Echocardiogram or multigated acquisition scan (MUGA) demonstrating an ejection fraction ≥ 45%.
    12. Patients with prior autologous and allogeneic bone marrow transplant are eligible. Patients with an allogeneic transplant must meet the following conditions: The transplant must have been performed more than 120 days before the date of dosing on this study, the patient must not have active ≥ Grade 2 graft versus host disease, and the patient must be off all systemic immunosuppression for at least 2 weeks before dosing.
    1. El paciente debe ser ≥ 18 años.
    2. Los pacientes deben tener un diagnóstico confirmado de LMA (excluida la leucemia promielocítica aguda) de acuerdo con la clasificación de la Organización Mundial de la Salud.
    3. Características de la enfermedad y terapia previa permitida:
    a. Los pacientes deben ser evaluados para los tratamientos de referencia disponibles y deben considerarse adecuados para este tratamiento experimental según el criterio del médico a cargo del tratamiento.
    b. Los pacientes sin tratamiento previo podrán ingresar en la Fase de Expansión del Régimen A (IMGN632 + azacitidina) y del Régimen C (IMGN632 + azacitidina + venetoclax). No se permiten tratamientos anteriores con agentes hipometilantes para el síndrome mielodisplásico.
    c. Los pacientes deberán tener LMA CD123 positiva confirmada por citometría de flujo local (o inmunohistoquímica [IHC]).
    d. Los pacientes pueden haber recibido terapias dirigidas contra CD123 previas, excepto IMGN632, siempre y cuando CD123 siga siendo detectable durante la selección.
    e. Los pacientes con LMA recidivante podrán ser incluidos en la Fase de Escalado de los Regímenes A, B y C (IMGN632 + azacitidina, venetoclax, o azacitidina + venetoclax, respectivamente) y en la Fase de Expansión para los Regímenes A y B y pueden haber recibido hasta 2 líneas de terapia previas, por ejemplo, tratamiento de primera línea (inducción, consolidación [incluido el trasplante], y el mantenimiento) y 1 régimen de rescate.
    f. Los pacientes incluidos en el Régimen D deben estar en RC (RC/RCi) durante no más de 6 meses y con EMR+, confirmada por el laboratorio central, tras la terapia intensiva de inducción/consolidación.
    4. Los pacientes incluidos en el Régimen D (LMA EMR+) primero deben tener una muestra de cribado de médula ósea evaluable confirmada como EMR+ por el test de EMR del laboratorio central.
    5. Tener un estado funcional del Eastern Cooperative Oncology Group (ECOG) ≤ 1. Si no pudiera ser ambulatorio por una discapacidad crónica, deberá tener un estado funcional Karnofsky > 70.
    6. Las toxicidades relacionadas con el tratamiento previo deben haberse resuelto a Grado 1 o a estado basal (excluyendo alopecia).
    7. El recuento leucocitario debe ser menor a 25 x 10e9 células/L. El uso de hidroxiurea está permitido para controlar los recuentos sanguíneos antes del Ciclo 1 Día 1, a discreción del médico tratante, según la práctica habitual del centro. Durante la Fase de Escalado de los Regímenes A-C puede utilizarse la hidroxiurea durante el Ciclo 1.
    8. Tener un nivel de enzimas hepáticas (ALT y AST) ≤ 3 veces el límite superior de la normalidad (LSN).
    9. Tener un nivel de bilirrubina total ≤ 1.5 veces el LSN durante los 14 días previos a la inclusión.
    10. Tener un nivel de creatinina sérica ≤ 1.5 mg/dL durante los 14 días previos a la inclusión.
    11. Tener una fracción de eyección ventricular izquierda (FEVI) > 45 % evaluada mediante ecocardiograma (Ecocardio) o ventriculografía nuclear (VRN).
    12. Los pacientes con trasplante de médula ósea autólogo o alogénico previo son elegibles. Los pacientes con trasplante alogénico deben cumplir los siguientes requisitos: El trasplante debe haberse realizado más de 120 días antes de la fecha de la primera dosis en este estudio, el paciente no debe tener enfermedad activa del injerto contra el huésped ≥ Grado 2, y el paciente debe estar fuera de toda inmunosupresión sistémica durante al menos 2 semanas antes del tratamiento de estudio.
    E.4Principal exclusion criteria
    1. Patients who have received any anticancer therapy, including investigational agents, within 14 days (or within 28 days for checkpoint inhibitors) before drug administration on this study (hydroxyurea is allowed before beginning study treatment). Patients must have recovered to baseline from all acute toxicity from this prior therapy.
    2. Patients who have been previously treated with IMGN632.
    3. Patients with myeloproliferative neoplasm–related secondary AML are excluded from the Dose Expansion Phase of the study.
    4. Patients with active central nervous system (CNS) AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgement. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor.
    5. Patients with a history of sinusoidal obstruction syndrome/venous occlusive disease of the liver.
    6. Myocardial infarction within 6 months before enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities before study entry.
    7. Clinically relevant active infection including known active hepatitis B or C, HIV infection, or cytomegalovirus or any other known concurrent infectious disease that, in the judgment of the investigator, would make a patient inappropriate for enrollment into this study (testing not required).
    8. Patients who have undergone a major surgery within 4 weeks (or longer if not fully recovered) before study enrollment.
    1. Los pacientes que hayan recibido cualquier terapia anticancerígena, incluyendo agentes en investigación, dentro de los 14 días (o dentro de 28 días para inhibidores controlados) previos a la administración del fármaco del estudio (la hidroxiurea está permitida antes del inicio del tratamiento del estudio). Los pacientes deben haber recuperado su estado basal de todas las toxicidades agudas de esta terapia previa.
    2. Los pacientes que hayan sido tratados previamente con IMGN632.
    3. Los pacientes con neoplasmo mieloproliferativo relacionado con LMA secundaria estarán excluidos de la Fase de Expansión de Dosis de este estudio.
    4. Los pacientes con afectación por LMA del sistema nervioso central (SNC) están excluidos. No es necesaria una punción lumbar a no ser que haya una sospecha clínica de afectación del SNC a criterio del investigador. La terapia concurrente para la profilaxis del SNC o la continuación de la terapia para la LMA del SNC controlada se permite con la aprobación del promotor.
    5. Pacientes con antecedentes de síndrome de obstrucción sinusoidal/enfermedad oclusiva venosa del hígado.
    6. Infarto de miocardio dentro de los 6 meses anteriores a la inclusión o insuficiencia cardíaca de clase III o IV de la New York Heart Association, angina no controlada, arritmias ventriculares no controladas graves o evidencia electrocardiográfica de isquemia aguda o anormalidades en el sistema de conducción activa antes de la inclusión en el estudio.
    7. Infecciones activas clínicamente relevantes como hepatitis B o C activas, infección por VIH, o citomegalovirus o cualquier otra infección concurrente que, en opinión del investigador, haga inapropiada la inclusión del paciente en este estudio (pruebas no necesarias).
    8. Pacientes que se han sometido a una cirugía mayor dentro de las 4 semanas (o más si no se han recuperado completamente) antes de la inclusión en el estudio.
    E.5 End points
    E.5.1Primary end point(s)
    1. Dose Escalation Cohorts
    a. RP2D of IMGN632 when administered in combination with azacitidine azacitidine (Regimen A), venetoclax (Regimen B), azacitidine+venetoclax (Regimen C)
    b. Treatment-emergent adverse events (TEAEs), laboratory test results, physical examination, electrocardiograms (ECGs), and vital signs

    2. Dose Expansion Cohorts
    a. Regimen A (IMGN632+azacitidine), Regimen B (IMGN632+ venetoclax), Regimen C (IMGN632+ azacitidine+venetoclax)
    i. Full CR (CRMRD- or CR) rate, best response (CRMRD-, CR, CRh, complete remission with incomplete recovery [CRi], morphologic leukemia-free state [MLFS], partial response [PR]), and duration of response (DOR)
    ii. MRD levels using central flow cytometry–based testing
    b. Regimen D (IMGN632 monotherapy in MRD+ maintenance)
    i. MRD+ to MRD- conversion rate, relapse-free survival (RFS) in patients with MRD+ AML
    1. Cohortes de Escalado de Dosis
    a. Dosis Recomendada para la Fase 2 (RP2D) de IMGN632 cuando se administra en combinación con azacitidina (Régimen A), venetoclax (Régimen B), azacitidina + venetoclax (Régimen C).
    b. Acontecimientos adversos que surjan durante el tratamiento (TEAEs por sus siglas en inglés), resultados de test de laboratorio, exámenes físicos, electrocardiogramas (ECGs), y signos vitales.

    2. Cohortes de Expansión de Dosis
    a. Régimen A (IMGN632 + azacitidina), Régimen B (IMGN632 + venetoclax), Régimen C (IMGN632 + azacitidina + venetoclax)
    i. Ratio de RC completa (RC EMR- o RC), mejor respuesta (RC EMR-, CR, RCh, respuesta completa con recuperación incompleta [RCi], estado morfológico libre de leucemia [MLFS], respuesta parcial [RP]), y la duración de la respuesta (DOR).
    ii. Niveles de EMR utilizando las pruebas de citometría de flujo central.
    b. Régimen D (mantenimiento con IMGN632 en monoterapia con EMR+)
    i. Tasa de conversión de EMR+ a EMR-, supervivencia libre de recaída (RFS) en pacientes con LMA EMR+.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Safety and Tolerability are assessed throughout the study and at the end of the treatment and end of the study
    2. Anti-tumor activity data will be collected at the end of each cycle until a response or progression has reached.
    1. La Seguridad y la Tolerabilidad se evalúan a lo largo del estudio, al final del tratamiento y al final del estudio.
    2. Los datos de actividad antitumoral se recogerán al final de cada ciclo hasta que se alcance una respuesta o progresión.
    E.5.2Secondary end point(s)
    1. Dose Escalation+ Dose Expansion Cohorts
    a. Regimen A (IMGN632+azacitidine), Regimen B (IMGN632+ venetoclax), Regimen C (IMGN632+ azacitidine+venetoclax )
    i. TEAEs
    ii. IMGN632 PK parameters for intact ADC, total antibody, and free payload (FGN849) include, but are not limited to, Cycle 1 and Cycle 3 maximum plasma concentration (Cmax), area under the time-concentration curve (AUC), terminal half-life (t½), clearance (CL), volume of distribution at steady state (Vss), and time that Cmax occurs (tmax)
    iii. Blood concentration of azacitidine, venetoclax, azacitidine and venetoclax measured before and after their administration
    iv. ADA response
    v. MRD levels using central flow cytometry–based testing during dose escalation
    b. Regimen D (IMGN632 monotherapy in MRD+ maintenance)
    i. IMGN632 PK parameters for intact ADC, total antibody, and free payload (FGN849) include, but are not limited to, Cycle 1 and Cycle 3 Cmax, AUC, t½, CL, Vss, and tmax
    ii. ADA response
    1. Escalado de Dosis + Cohortes de Expansión de Dosis
    a. Régimen A (IMGN632 + azacitidina), Régimen B (IMGN632 + venetoclax), Régimen C (IMGN632+ azacitidina + venetoclax)
    i. Acontecimientos adversos que surjan durante el tratamiento (TEAEs)
    ii. Los parámetros IMGN632 PK para ADC intacto, anticuerpos totales y carga útil libre (FGN849) incluyen, pero no se limitan a, Concentración plasmática máxima del Ciclo 1 y Ciclo 3 (Cmax), área bajo la curva de concentración-tiempo (AUC), vida media terminal (t½), aclaramiento (CL), volumen de distribución en estado estacionario (Vss) y tiempo en el que ocurre el Cmax (tmax).
    iii. Concentración en sangre de azacitidina, venetoclax, y azacitidina y venetoclax medido antes y después de su administración.
    iv. Respuesta ADA.
    v. Niveles de EMR utilizando los test de citometria de flujo central durante el escalado de dosis.
    b. Régimen D (mantenimiento con IMGN632 en monoterapia con EMR+)
    i. Los parámetros IMGN632 PK para ADC intacto, anticuerpos totales y carga útil libre (FGN849) incluyen, pero no se limitan a, Cmax del Ciclo 1 y Ciclo 3, AUC, t½, CL, Vss y tmax.
    ii. Respuesta ADA.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Safety and Tolerability are assessed throughout the study and at the end of the treatment and end of the study

    2. Anti-tumor activity data will be collected at the end of each cycle until a response or progression has reached.
    1. La Seguridad y la Tolerabilidad se evalúan a lo largo del estudio, al final del tratamiento y al final del estudio.
    2. Los datos de actividad antitumoral se recogerán al final de cada ciclo hasta que se alcance una respuesta o progresión.
    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 Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase 1b/2 safety and tolerability
    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 No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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 trial4
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    France
    Germany
    Italy
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study will be defined as the latter of the completion of the safety follow-up visit for the last patient remaining on treatment or 1 year from the last accrued patient’s first visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months21
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months21
    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: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 162
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 212
    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)
    There are no plans for treatment or care after subjects have ended their participation in the study.
    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 Decision2020-01-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-12-18
    P. End of Trial
    P.End of Trial StatusOngoing
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA