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    Summary
    EudraCT Number:2020-004954-31
    Sponsor's Protocol Code Number:DS3201-A-U202
    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:2021-08-04
    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 number2020-004954-31
    A.3Full title of the trial
    Single-Arm, Phase 2 Study of Valemetostat Tosylate Monotherapy in Subjects with Relapsed/Refractory Peripheral T-Cell Lymphoma
    Estudio de fase 2 de un solo brazo en monoterapia con tosilato de valemetostat en sujetos con linfoma periférico de células T en recaída / refractario
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of Valemetostat Tosylate Monotherapy in Subjects with Relapsed/Refractory Peripheral T-Cell Lymphoma
    Estudio de tosilato de valemetostat en sujetos con linfoma periférico de células T en recaída / refractario
    A.3.2Name or abbreviated title of the trial where available
    Valemetostat tosylate (DS-3201b), an enhancer of zeste homolog (EZH) 1/2 dual inhibitor, for R/R PTC
    Valemetostat tosilato [DS-3201b], un inhibidor dual del potenciador del homólogo Zeste [EZH] 1/2
    A.4.1Sponsor's protocol code numberDS3201-A-U202
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04703192
    A.5.4Other Identifiers
    Name:IND numberNumber:132312
    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 SponsorDAIICHI SANKYO, 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 supportDAIICHI SANKYO, INC.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDAIICHI SANKYO, INC.
    B.5.2Functional name of contact pointClinical Trial Information Contact
    B.5.3 Address:
    B.5.3.1Street Address211 Mt. Airy Road
    B.5.3.2Town/ cityBasking Ridge, New Jersey
    B.5.3.3Post codeNJ 07920-2311
    B.5.3.4CountryUnited States
    B.5.4Telephone number+19089926400
    B.5.6E-maileu-cta@dsi.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 nameValemetostat tosylate
    D.3.2Product code DS-3201b
    D.3.4Pharmaceutical form Film-coated 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 INNValemestostat Tosylate
    D.3.9.1CAS number 1809336-93-3
    D.3.9.2Current sponsor codeDS-3201b
    D.3.9.3Other descriptive nameValemetostat tosylate
    D.3.9.4EV Substance CodeSUB194708
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP 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 nameValemetostat tosylate
    D.3.2Product code DS-3201b
    D.3.4Pharmaceutical form Film-coated 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 INNValemestostat Tosylate
    D.3.9.1CAS number 1809336-93-3
    D.3.9.2Current sponsor codeDS-3201b
    D.3.9.3Other descriptive nameValemetostat tosylate
    D.3.9.4EV Substance CodeSUB194708
    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
    Relapsed/Refractory Peripheral T-Cell Lymphoma
    linfoma periférico de células T en recaída / refractario
    E.1.1.1Medical condition in easily understood language
    Relapsed/Refractory Peripheral T-Cell Lymphoma
    linfoma periférico de células T en recaída / refractario
    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 PT
    E.1.2Classification code 10025310
    E.1.2Term Lymphoma
    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 estimate the objective response rate (ORR) with valemetostat tosylate monotherapy treatment in R/R PTCL, including R/R ATL. Subjects with R/R ATL are to be enrolled in a separate cohort and will be analyzed independently.
    Estimar la tasa de respuesta objetiva (TRO) con el tratamiento con tosilato de valemetostat en monoterapia en el LLTP R/R, incluida la ALT R/R. Los pacientes con ALT R/R deben inscribirse en una cohorte independiente y se analizarán de forma independiente.
    E.2.2Secondary objectives of the trial
    - To evaluate the duration of response (DoR);
    - To assess the CR rate;
    - To evaluate the duration of CR (DoCR);
    - To assess the PR rate;
    - To assess the safety and tolerability of valemetostat tosylate monotherapy.
    -Evaluar la duración de la respuesta (DR).
    -Evaluar la tasa de RC
    -Evaluar la duración de la RC (DRC)
    -Evaluar la tasa de RP
    -Evaluar la seguridad y tolerabilidad de la monoterapia con tosilato de valemetostat
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Sign and date the ICF, prior to the start of any study-specific qualification procedures.
    2. Subjects ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
    3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
    4. Cohort 1 (R/R PTCL): Should be pathologically confirmed by the local pathologist/investigators; local histological diagnosis will be used for eligibility determination. Subjects with the following subtypes of PTCL are eligible, according to 2016 World Health Organization classification prior to the initiation of study drug. Any T-cell lymphoid malignancies not listed below are excluded. Below is the complete list of eligible subtypes:
    - Enteropathy-associated T-cell lymphoma
    - Monomorphic epitheliotropic intestinal T-cell lymphoma
    - Hepatosplenic T-cell lymphoma
    - Primary cutaneous γδ T-cell lymphoma
    - Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma
    - PTCL, not otherwise specified
    - Angioimmunoblastic T-cell lymphoma
    - Follicular T-cell lymphoma
    - Nodal PTCL with TFH phenotype
    - Anaplastic large cell lymphoma, ALK positive
    - Anaplastic large cell lymphoma, ALK negative
    5. Cohort 2 (R/R ATL): (acute, lymphoma, or unfavorable chronic type). R/R ATL should be pathologically or hematocytologically confirmed by the local pathologist/investigators; local histological/ hematocytologically diagnosis will be used for eligibility determination. The positivity of anti-HTLV-1 antibody will be locally determined for eligibility.
    6. Must have at least 1 of the following lesions which are measurable in 2 perpendicular dimensions on CT (or MRI) based on local radiological read:
    - Longest diameter (LDi) ≥2.0 cm for a nodal lesion
    - LDi >1.0 cm for an extranodal lesion
    For Cohort 2 (ATL), subjects who had disease only in peripheral blood or/and skin lesions are eligible, as defined below.
    o An abnormal lymphocyte count (actual number) is ≥1.0 × 10^9 /L and the abnormal lymphocyte-to-leucocyte ratio is ≥5%.
    o Skin lesion(s) measured by modified severity weighted assessment tool (mSWAT) score.
    7. Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy.
    Refractory is defined as
    • Failure to achieve CR (or uncertified CR [CRu] for ATL) from prior systemic lymphoma therapy, or relapsed disease (after CR or CRu for ATL), or progressive disease (after first-line therapy
    • Failure to reach at least PR or stable disease).following second-line therapy or beyond
    8. Must have at least 1 prior line of systemic therapy for PTCL or ATL.
    • Subjects must also be considered as HCT ineligible during Screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented.
    • In Cohort 1, subjects with ALCL must have prior brentuximab vedotin treatment.

    Please refer to the protocol for the full list of inclusion criteria.
    1. Firmar y fechar el ICF, antes del inicio de cualquier procemiento especifico del estudio
    2. Sujetos >/=18 años de edad o edad minima legal (la que sea mayor) en el momento de la firma del ICF
    3. Estado funcional de 0, 1 o 2 según el Grupo Oncológico Cooperativo del Este (Eastern Cooperative Oncology Group, ECOG).
    4. Cohorte 1 (LLTP R/R): Debe ser confirmada patológicamente por el anatomopatólogo/investigador local; el diagnóstico histológico local se utilizará para determinar la aptitud. Los sujetos con los siguientes subtipos de LLTP son aptos según la clasificación de la OMS de 2016 antes del inicio del fármaco del estudio. Cualquier neoplasia maligna linfoide de linfocitos T que no se mencione a continuación queda excluida. A continuación, se muestra la lista completa de los subtipos aptos:
    -Linfoma de linfocitos T asociado a enteropatía
    -Linfoma intestinal de linfocitos T monomórfico epiteliotrópico
    -Linfoma hepatoesplénico de linfocitos T
    -Linfoma cutáneo de linfocitos T γδ primario
    -Linfoma cutáneo de linfocitos T primario CD8+ epidermotrópico agresivo citotóxico
    -LLTP, sin especificar
    -Linfoma de linfocitos T angioinmunoblástico
    -Linfoma de linfocitos T folicular
    -LLTP ganglionar con fenotipo de linfocitos T cooperadores (T-follicular helper, TFH)
    -Linfoma anaplásico de células grandes, positivo para cinasa de linfoma anaplásico (anaplastic lymphoma kinase, ALK)
    -Linfoma anaplásico de células grandes, negativo para cinasa de linfoma anaplásico (anaplastic lymphoma kinase, ALK)
    5. Cohorte 2 (ATL R/R): aguda, linfoma o tipo crónico desfavorable. La ATL R/R debe ser confirmada patológica o hematocitologógicamente por el anatomopatólogo/investigador local; el diagnóstico mediante histología/hemocitología local se utilizará para determinar la aptitud. La positividad del anticuerpo anti- virus linfotrópico T humano de tipo 1 (HTLV-1) se determinará localmente para establecer la aptitud.
    6. Deben tener, al menos, una de las siguientes lesiones que sean medibles en 2 dimensiones perpendiculares en la tomografía axial computarizada (o resonancia magnética) según la lectura radiológica local:
    − Diámetro mayor (DM) >/=2,0 cm para una lesión ganglionar
    − DM >1,0 cm para una lesión extraganglionar
    Para la cohorte 2 (ATL), los pacientes que presentaban enfermedad solo en sangre periférica y/o lesiones cutáneas son aptos según las condiciones descritas a continuación.
    -Un recuento anormal de linfocitos (número real) es >/=1,0 × 109/l y la relación anómala entre linfocitos y leucocitos es >/=5 %.
    -Lesión(es) cutánea(es) medida(s) mediante la puntuación de la herramienta de evaluación ponderada por gravedad modificada.
    7. Enfermedad resistente, recidivante o progresiva confirmada después de al menos 1 línea previa de tratamiento sistémico.
    El término recidivante se define de la siguiente manera:
    - Fracaso en la consecución de RC (o RCsc para el ATL) después del tratamiento de primera línea.
    - Fracaso en la consecución de al menos RP tras la segunda línea de tratamiento o posterior.
    8. Debe haber recibido, al menos, 1 línea previa de tratamiento sistémico para LLTP o ATL.
    Los sujetos deben ser considerados no aptos para el trasplante de células hematopoyéticas (TCH) durante la selección debido al estado de la enfermedad (enfermedad activa), comorbilidades u otros factores; el motivo por el que el paciente no es apto para el TCH debe documentarse claramente.
    En la cohorte 1, los pacientes con linfoma anaplásico de células grandes (LACG) deben haber recibido tratamiento previo con brentuximab vedotina.

    Para la lista completa de criterios por favor refiérase al protocolo
    E.4Principal exclusion criteria
    1. Diagnosis of mycosis fungoides, Sézary syndrome, and primary cutaneous ALCL and systemic dissemination of primary cutaneous ALCL
    2. Diagnosis of precursor T-cell lymphoblastic leukemia and lymphoma (T-cell acute lymphoblastic leukemia and T-cell lymphoblastic leukemia), T-cell prolymphocytic leukemia, or T-cell large granular lymphocytic leukemia
    3. Prior malignancy active within the previous 2 years except for locally curable cancer that is currently considered as cured, such as cutaneous basal or squamous cell carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental histological finding of prostate cancer
    4. Presence of active central nervous system (CNS) involvement of lymphoma
    5. History of autologous HCT within 60 days prior to first dose of study drug
    6. History of allogeneic HCT within 90 days prior to the first dose of study drug
    7. Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic immunosuppressive prophylaxis or treatment
    8. Inadequate washout period from prior lymphoma-directed therapy before enrollment, defined as follows:
    - Prior systemic therapy (eg, chemotherapy, immunomodulatory therapy, or monoclonal antibody therapy) within 3 weeks prior to the first dose of study drug
    - Had curative radiation therapy or major surgery within 4 weeks or palliative radiation therapy within 2 weeks prior to the first dose of study drug
    9. Uncontrolled or significant cardiovascular disease, including the following:
    - Evidence of prolongation of QT/QTc interval (eg, repeated episodes of QT corrected for heart rate using Fridericia’s method [QTcF] >450 ms) (average of triplicate determinations)
    - Diagnosed or suspected long QT syndrome, or known family history of long QT syndrome
    - History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes
    - Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrial fibrillation may be enrolled), or asymptomatic persistent ventricular tachycardia
    - Subject has clinically relevant bradycardia of <50 bpm unless the subject has a pacemaker
    - History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers, and have no history of fainting or clinically relevant arrhythmia with pacemakers, within 6 months prior to Screening
    - Myocardial infarction within 6 months prior to Screening
    - Angioplasty or stent graft implantation within 6 months prior to Screening
    - Uncontrolled angina pectoris within 6 months prior to Screening
    - New York Heart Association (NYHA) Class 3 or 4 congestive heart failure
    - Coronary/peripheral artery bypass graft within 6 months prior to Screening
    - Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
    - Complete left or right bundle branch block
    10. History of treatment with other EZH inhibitors
    11. Current use of moderate or strong cytochrome P450 (CYP)3A inducers (Table 10.4)
    12. Systemic treatment with corticosteroids (>10 mg daily prednisone equivalents). Note: Short-course systemic corticosteroids (eg, prevention/treatment for transfusion reaction) or use for a non-cancer indication (eg, adrenal replacement) is permissible.

    Please refer to the protocol for the full list of exclusion criteria.
    1.Diagnóstico de micosis fungoide, síndrome de Sézary y LACG cutáneo primario y diseminación sistémica de LACG cutáneo primario.
    2.Diagnóstico de leucemia y linfoma linfoblásticos de precursores de linfocitos T (leucemia linfoblástica aguda de linfocitos T y linfoma linfoblástico de linfocitos T), leucemia prolinfocítica de linfocitos T o leucemia linfocítica granular grande de linfocitos T.
    3.Neoplasia maligna previa activa en los 2 años anteriores, excepto cáncer localmente curable evaluado como curado, como carcinoma cutáneo basocelular o carcinoma epidermoide, cáncer superficial de vejiga o carcinoma cervicouterino in situ, o un hallazgo histológico casual de cáncer de próstata.
    4.Presencia de afectación activa del sistema nervioso central por el linfoma.
    5.Antecedentes de trasplante autólogo de células hematopoyéticas (TCH) en los 60 días anteriores a la primera dosis del fármaco del estudio.
    6.Antecedentes de TCH alogénico en los 90 días previos a la primera dosis del fármaco del estudio.
    7.Enfermedad de injerto contra huésped (EICH) clínicamente significativa o EICH que requiera profilaxis o tratamiento inmunosupresor sistémico. 8.Periodo de reposo farmacológico inadecuado del tratamiento anterior dirigido al linfoma antes de la inscripción, según los criterios siguientes:
    -Tratamiento sistémico previo (p. ej., quimioterapia, tratamiento inmunomodulador o tratamiento con anticuerpos monoclonales) en las 3 semanas previas a la primera dosis del fármaco del estudio.
    -Haber recibido radioterapia curativa o cirugía mayor en las 4 semanas previas o radioterapia paliativa en las 2 semanas previas a la primera dosis del fármaco del estudio.
    9.Enfermedad no controlada o enfermedad cardiovascular significativa, incluyendo:
    -Indicios de prolongación del intervalo QT/Qtc (p. ej., episodios repetidos de QT corregido para la frecuencia cardíaca utilizando el método de Fridericia >450 ms) (media de determinaciones por triplicado).
    -Diagnóstico o sospecha de síndrome de QT largo o antecedentes familiares conocidos de síndrome de QT largo.
    -Antecedentes de arritmias ventriculares clínicamente relevantes, como taquicardia ventricular, fibrilación ventricular o Torsade de Pointes.
    -Arritmia no controlada (se puede inscribir a sujetos con fibrilación auricular asintomática controlable) o taquicardia ventricular persistente asintomática.
    -El sujeto tiene bradicardia clínicamente relevante de <50 lpm, a menos que el sujeto tenga un marcapasos.
    -Antecedentes de bloqueo cardíaco de segundo o tercer grado. Los candidatos con antecedentes de bloqueo cardíaco pueden ser aptos si actualmente tienen marcapasos y no tienen antecedentes de desmayo o arritmia clínicamente relevante con marcapasos en los 6 meses anteriores a la selección.
    -Infarto de miocardio en los 6 meses anteriores a la selección.
    Angioplastia o implantación de stent en los 6 meses anteriores a la selección.
    -Angina de pecho no controlada en los 6 meses anteriores a la selección.
    -Insuficiencia cardíaca congestiva de clase III o IV según la New York Heart Association.
    -Revascularización coronaria/arterial periférica en los 6 meses anteriores a la selección.
    -Hipertensión no controlada (tensión arterial sistólica en reposo >180 mmHg y/o tensión arterial diastólica en reposo >110 mmHg).
    -Bloqueo completo de rama izquierda o derecha
    10.Antecedentes de tratamiento con otros inhibidores de EZH
    11.Uso actual de inductores moderados o potentes del citocromo P450 (CYP)3A (Tabla 10.4)
    12.Tratamiento sistémico con corticoesteroides (equivalentes a >10 mg diarios de prednisona). Nota: Se permite el uso de corticoesteroides sistémicos de corta duración (p. ej., prevención/tratamiento para la reacción a la transfusión) o uso para una indicación distinta al cáncer (p. ej., sustitución suprarrenal).

    Para la lista completa de criterios por favor refiérase al protocolo
    E.5 End points
    E.5.1Primary end point(s)
    Cohort 1
    ORR is defined as the proportion of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR), assessed by BICR, among subjects with centrally confirmed PTCL-eligible histology.

    Cohort 2
    ORR is defined as the proportion of subjects with a BOR of CR, uncertified CR (CRu), or PR, assessed by BICR, among subjects with centrally confirmed histology/peripheral blood assessment.
    Cohorte 1
    La TRO se define como la proporción de sujetos con una mejor respuesta global (MRG) de respuesta completa (RC) o respuesta parcial (RP), evaluada mediante RCIE, entre los sujetos con histología acorde a LLTP confirmada centralmente.

    Cohorte 2
    La TRO se define como la proporción de sujetos con una MRG de RC, RC sin certificar (RCsc) o RP, evaluada mediante RCIE, entre los sujetos con anticuerpos positivos contra el virus de la leucemia de linfocitos T humano (HTLV-1).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Cohort 1: At least 10 months after the first dose of valemetostat tosylate of the last subject enrolled into Cohort 1

    Cohort 2: At least 10 months after the first dose of valemetostat tosylate of the last subject enrolled into Cohort 2
    Cohorte 1: Como mínimo 10 meses después de la primera dosis de tosilato de valemetostat del último paciente inscrito en la cohorte 1.
    Cohorte 2: Como mínimo 10 meses después de la primera dosis de tosilato de valemetostat del último paciente inscrito en la cohorte 2.
    E.5.2Secondary end point(s)
    - DoR is defined as the time from the date of the first documentation of objective response (CR, CRu [ATL only] or PR) to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first.
    - Complete response rate is the percentage of subjects achieving CR (and CRu, in Cohort 2) as the BOR based on BICR.
    - DoCR, is defined as the time from the date of the first documentation of CR (also CRu, in Cohort 2) to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs
    first.
    - Partial response rate is the percentage of subjects achieving PR as the BOR based on BICR assessment.
    - All safety assessments, including AE reporting (TEAEs; treatment-emergent adverse events of special interest [TEAESI]; treatment emergent serious adverse events [TESAEs]; TEAEs by severity [CTCAE grading, including Grade 3 and Grade 4]; fatal events; and TEAEs leading to treatment discontinuation, interruption, or reduction), laboratory assessments, vital signs and electrocardiogram (ECG) (including corrected QT interval [QTcF] by central ECG reading)
    -La DR se define como el tiempo transcurrido desde la fecha de la primera documentación de respuesta objetiva (RC, RCsc [solo ATL] o RP) hasta la fecha de la primera documentación de progresión de la enfermedad (enfermedad progresiva o recidivante) en base a las evaluaciones de RCIE o hasta la muerte por cualquier causa, lo que ocurra primero.
    -La tasa de respuesta completa es el porcentaje de sujetos que logran RC (y RCsc, en la cohorte 2) como MRG según las evaluaciones de RCIE.
    -La DRC se define como el tiempo transcurrido desde la fecha de la primera documentación de RC (también RCsc en la cohorte 2) hasta la fecha de la primera documentación de progresión de la enfermedad (enfermedad progresiva o recidivante) en base a las evaluaciones de RCIE o hasta la muerte por cualquier causa, lo que ocurra primero.
    -La tasa de respuesta parcial es el porcentaje de sujetos que logran RC como MRG según las evaluaciones de RCIE.
    -Todas las evaluaciones de la seguridad, incluida la notificación de AA (AAST; acontecimientos adversos surgidos durante el tratamiento de interés especial [AASTIE]; acontecimientos adversos graves surgidos durante el tratamiento [AAGST]; AAST según la intensidad [Criterios terminológicos comunes para acontecimientos adversos {Common Terminology Criteria for Adverse Events, CTCAE}, incluidos grado 3 y grado 4], pruebas analíticas, constantes vitales y electrocardiograma (ECG) (incluido el intervalo QT corregido [QTcF] mediante lectura central del ECG)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Cohort 1: At least 10 months after the first dose of the last subject enrolled into Cohort 1

    Cohort 2: At least 10 months after the first dose of the last subject enrolled into Cohort 2
    Cohorte 1: Como mínimo 10 meses después de la primera dosis del último sujeto inscrito en la cohorte 1.
    Cohorte 2: Como mínimo 10 meses después de la primera dosis del último sujeto inscrito en la cohorte 2.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Este estudio incluirá 2 cohortes
    This study will include 2 cohorts
    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 trial1
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Canada
    France
    Germany
    Italy
    Japan
    Korea, Republic of
    Netherlands
    Spain
    Taiwan
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The last subject’s last visit is defined as the completion of survival follow-up of at least 3 years after the first dose of the last subject either from Cohort 1 or Cohort 2, whichever occurs later.
    The subject’s EOS is defined as the date of his/her last study visit/contact.
    La última visita del último paciente se define como la finalización del seguimiento de la supervivencia de, al menos, 3 años después de la primera dosis del último sujeto, ya sea de la cohorte 1 o de la cohorte 2, lo que ocurra más tarde.
    El FdE del sujeto se define como la fecha de su última visita/contacto del estudio.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days0
    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: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 106
    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 state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 176
    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)
    Subject will be treated as clinically indicated by investigator after the study
    Los sujetos serán tratados según lo indicado clinicamente por el investigador después 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 Decision2021-08-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-08
    P. End of Trial
    P.End of Trial StatusOngoing
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