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    Summary
    EudraCT Number:2021-000870-27
    Sponsor's Protocol Code Number:D361FC00001
    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:2021-06-23
    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 number2021-000870-27
    A.3Full title of the trial
    A Modular Phase II, Open-Label, Multicentre Study to Assess the Efficacy and Safety of Capivasertib in Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (CAPITAL)
    Estudio de fase II, modular, abierto y multicéntrico para evaluar la eficacia y la seguridad del capivasertib en pacientes con linfoma no Hodgkin de células B en recidiva o refractario (CAPITAL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase 2 trial to study safety and efficacy of Capivasertib in patients with blood cancer where disease or cancer cell grows after a period of remission or response to treatment does not last very long
    Ensayo de fase 2 para evaluar la seguridad y la eficacia del capivasertib en pacientes con cáncer de la sangre cuya enfermedad o las células del cáncer hayan vuelto a crecer tras un periodo de remisión o de respuesta al tratamiento de duración no muy prolongada
    A.3.2Name or abbreviated title of the trial where available
    CAPITAL
    CAPITAL
    A.4.1Sponsor's protocol code numberD361FC00001
    A.5.4Other Identifiers
    Name:INDNumber:154612
    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 SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    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 supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca
    B.5.2Functional name of contact pointClinical Study Information Center
    B.5.3 Address:
    B.5.3.1Street AddressN/A
    B.5.3.2Town/ cityN/A
    B.5.3.3Post codeN/A
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1877 240 9479
    B.5.6E-mailInformation.Center@astrazeneca.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 nameCapivasertib
    D.3.2Product code AZD5363
    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 INNCapivasertib
    D.3.9.1CAS number 1143532-39-1
    D.3.9.2Current sponsor codeAZD5363
    D.3.9.3Other descriptive nameAZ12952302
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    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 nameCapivasertib
    D.3.2Product code AZD5363
    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 INNCapivasertib
    D.3.9.1CAS number 1143532-39-1
    D.3.9.2Current sponsor codeAZD5363
    D.3.9.3Other descriptive nameAZ12952302
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 or Refractory B-cell Non-Hodgkin Lymphoma
    Linfoma no Hodgkin de células B en recidiva o refractario
    E.1.1.1Medical condition in easily understood language
    Non-Hodgkin Lymphoma
    Linfoma no Hodgkin
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 24.0
    E.1.2Level LLT
    E.1.2Classification code 10067070
    E.1.2Term Follicular B-cell non-Hodgkin's lymphoma
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10076596
    E.1.2Term Marginal zone lymphoma
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10061275
    E.1.2Term Mantle cell 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 effectiveness of the module-defined study treatment by assessment of Objective Response Rate (ORR) based on Lugano 2014 Classification response criteria in each cohort as determined by Blinded Independent Central Review (BICR)
    Estimar la eficacia del tratamiento del estudio definido por módulos mediante la evaluación de la ORR basada en los criterios de respuesta de la clasificación de Lugano 2014 en cada cohorte, determinada por BICR.
    E.2.2Secondary objectives of the trial
    1. To estimate the effectiveness of the module-defined study-treatment by assessment of Duration of Response (DoR)
    2. To estimate the effectiveness of the module-defined study treatment by assessment of Progression-Free Survival (PFS)
    3. To estimate the effectiveness of the module-defined study treatment by assessment of Overall Survival (OS)
    4. To assess patient-reported disease-related symptoms, functioning and health-related quality of life of the module-defined study treatment
    5. To assess patient-reported symptomatic AEs / tolerability of module-defined study treatment
    6. To estimate the effectiveness of the module-defined study treatment by assessment of Time to First Subsequent therapy or death (TFST) in each cohort
    7. To estimate the effectiveness of the module-defined study treatment by assessment of time to objective response (TTR) in each cohort
    8. To assess safety and tolerability of the module-defined study treatment
    9. To determine the PK of Capivasertib
    1. Estimar la eficacia del tratamiento del estudio definido por módulos mediante la evaluación de la DoR.
    2. Estimar la eficacia del tratamiento del estudio definido por módulos mediante la evaluación de la PFS.
    3. Estimar la eficacia del tratamiento del estudio definido por módulos mediante la evaluación de la OS.
    4. Evaluar los síntomas de la enfermedad, la capacidad funcional y la calidad de vida relacionada con la salud, percibidos por el paciente, del tratamiento del estudio.
    5. Evaluar los AEs sintomáticos/tolerabilidad, percibidos por el paciente, del tratamiento del estudio definido por módulos.
    6. Estimar la eficacia del tratamiento del estudio definido por módulos mediante la evaluación del TFST en cada cohorte.
    7. Estimar la eficacia del tratamiento del estudio definido por módulos mediante la evaluación del TR en cada cohorte.
    8. Evaluar la seguridad y la tolerabilidad del tratamiento del estudio definido por módulos.
    9. Determinar la PK del capivasertib.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Patient must be >/= 18 years of age, at the time of signing the informed consent
    - ECOG performance status </= 2
    - Life expectancy > 6 months
    - Female patients must not be breast-feeding and must have a negative pregnancy test prior to start of dosing

    Additional core inclusion criteria may apply, please refer to the protocol.

    Module 1 specific inclusion criteria:

    Additional Inclusion Criteria for Cohort 1A (R/R FL):
    1. Histologically confirmed diagnosis of FL Grade 1, 2, or 3a as assessed by investigator or local pathologist
    2. Current need for systemic treatment based on the Investigator’s opinion
    3. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy (including anti-CD20mAb and an alkylating agent)
    4. Patients should have received up to a maximum of 5 lines of prior therapies.
    5. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis.

    Additional Inclusion Criteria for Cohort 1B (R/R MZL):
    1. Histologically confirmed MZL including splenic, nodal, and extranodal subtypes as assessed by investigator or local pathologist.
    2. Current need for systemic treatment based on the Investigator’s opinion.
    3. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy (including at least one anti-CD20mAb directed regimen either as monotherapy or as chemoimmunotherapy; Helicobacter pylori eradication and radiation therapy alone will not be considered a systemic treatment regimen).
    4. Patients should have received up to a maximum of 5 lines of prior therapies.
    5. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis.

    Additional Inclusion Criteria for Cohort 1C (R/R MCL):
    1. Histologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, as assessed by investigator or local pathologist.
    2. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy.
    3. Patients should have received up to a maximum of 4 lines of prior therapies.
    Prior regimens must have included:
    - BTK inhibitor and
    - Anti-CD20 monoclonal antibody therapy
    4. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis.
    - Paciente de edad >/= 18 años en el momento de la firma del consentimiento informado
    - Estado funcional del ECOG </= 2
    - Esperanza de vida > 6 meses
    - Si se trata de una mujer, no podrá estar amamantando y deberá mostrar una prueba de embarazo negativa antes del inicio del tratamiento

    Hay también otros criterios principales adicionales; para ello, sírvanse ver el protocolo.

    Criterios de inclusión específicos para el Módulo 1:

    Criterios de inclusión adicionales para la Cohorte 1A (LF R/R):
    1. LF, histológicamente confirmado, de Grado 1, 2 o 3a según el investigador o el anatomopatólogo local
    2. Necesidad actual de tratamiento sistémico en opinión del investigador
    3. Tumor que ha recidivado o progresado o que se ha mostrado refractario (lo que se define como no haber alcanzado como mínimo una respuesta parcial) tras como mínimo 2 líneas de tratamiento sistémico previas (incluidos un anticuerpo monoclonal anti-CD20 y un alquilante)
    4. Recepción de un máximo de 5 líneas previas de tratamiento.
    5. Enfermedad medible bidimensionalmente en los cortes transversales por TAC o RM, con como mínimo una lesión nodal de eje mayor > 1.5 cm o como mínimo una lesión extranodal de eje mayor> 1 cm.

    Criterios de inclusión adicionales para la Cohorte 1B (LZM R/R):
    1. LZM, histológicamente confirmado, incluidos subtipos esplénico, nodal y extranodal, según el investigador o el anatomopatólogo local.
    2. Necesidad actual de tratamiento sistémico en opinión del investigador.
    3. Tumor que ha recidivado o progresado o que se ha mostrado refractario (lo que se define como no haber alcanzado como mínimo una respuesta parcial) tras como mínimo 2 líneas de tratamiento sistémico previas (lo que incluye como mínimo un régimen con un anticuerpo monoclonal anti-CD20, ya sea en monoterapia o como quimioinmunoterapia; la erradicación del Helicobacter pylori y la radioterapia sola no se considerarán como tratamiento sistémico).
    4. Recepción de un máximo de 5 líneas previas de tratamiento.
    5. Enfermedad medible bidimensionalmente en los cortes transversales por TAC o RM, con como mínimo una lesión nodal > 1.5 cm en su eje mayor o como mínimo una lesión extranodal de eje mayor> 1 cm.

    Criterios de inclusión adicionales para la Cohorte 1C (LCM R/R):
    1. LCM, histológicamente confirmado, con documentación de células B monoclonales con translocación cromosómica t(11;14)(q13;q32) y/o hiperexpresión de ciclina D1, en opinión del investigador o del anatomopatólogo local.
    2. Tumor que ha recidivado o progresado o que se ha mostrado refractario (lo que se define como no haber alcanzado como mínimo una respuesta parcial) tras como mínimo 2 líneas de tratamiento sistémico previas.
    3. Recepción de un máximo de 4 líneas previas de tratamiento.
    Los regímenes previos deben haber incluido:
    - inhibidor de BTK y
    - tratamiento con anticuerpo monoclonal anti-CD20
    4. Enfermedad medible bidimensionalmente en los cortes transversales por TAC o RM, con como mínimo una lesión nodal de eje mayor > 1.5 cm o como mínimo una lesión extranodal de eje mayor > 1 cm.
    E.4Principal exclusion criteria
    - Prior malignancy (other than the disease under study), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the patient has been disease free for >/= 2 years
    - With the exception of alopecia, any unresolved non-haematological toxicities from prior therapy >/= CTCAE Grade 2 at the time of starting study treatment
    - Known medically apparent CNS lymphoma or leptomeningeal disease
    - Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values at screening:
    a) Absolute neutrophil count < 1.0 × 10^9/L; < 0.75 × 10^9/L in participants with known bone marrow involvement of malignant disease
    b) Platelets < 75 × 10^9/L; < 50 × 10^9/L in participants with known bone marrow involvement of malignant disease
    c) Creatinine clearance < 50 mL/min per the Cockcroft and Gault formula

    - Clinically significant abnormalities of glucose metabolism as participants with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment and Glycosylated haemoglobin >/= 8.0% (63.9 mmol/mol)
    - Prior treatment with any of the following:
    a) Any investigational agents or study drugs from a previous clinical study within 5 half lives or 2 weeks from the first dose of capivasertib in this study
    b) Potent inhibitors or inducers of CYP3A4 and/or UGT2B7 within 2 weeks prior to the first dose of study treatment (3 weeks for St John’s wort), or sensitive substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week prior to the first dose of study treatment.
    c) Prior allogenic HSCT within 6 months from the first dose of capivasertib (patients > 6 months after allogenic HSCT are eligible in the absence of active graft-versus-host disease and concomitant immune suppressive therapy). Prior cellular therapies (eg, CAR-T therapy) and/or autologous HSCT within 3 months from the first dose of capivasertib.
    d) Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment(s).
    e) Patients who, due to other medical conditions /prior history /concomitant medications are, in the investigator's opinion, at a risk of a VTE and are not willing to accept the VTE prophylaxis, will be excluded. The initiation of an adequate VTE prophylaxis will be based on treating physician risk/benefit assessment and in agreement with the local management guidelines.

    Additional exclusion core criteria may apply, please refer to the protocol

    Module 1 specific exclusion criteria:
    1. Follicular lymphoma grade 3B.
    2. Known transformation to aggressive lymphoma, eg, large cell lymphoma.
    3. MCL patients with blastoid or pleiomorphic variant or documented TP53 mutation at study entry/most recent relapse.
    4. Patients who, in the Investigator’s opinion, require immediate cytoreductive therapy for disease control
    - Neoplasia maligna previa (distinta de la enfermedad en estudio), excepción hecha del cáncer cutáneo de células basales o de células escamosas adecuadamente tratado, cáncer in situ u otro cáncer del que el paciente se encuentre sin enfermedad desde hace >/= 2 años
    - Con la excepción de alopecia, toda toxicidad no hematológica no resuelta del tratamiento previo de Grado >/= 2 de los CTCAE en el momento de iniciar el tratamiento del estudio
    - Evidencia médica de linfoma en SNC o de enfermedad leptomeníngea
    - Reserva de médula ósea o función orgánica no adecuadas, lo que se evidencia por cualquiera de los siguientes valores de laboratorio en la selección:
    a) recuento absoluto de neutrófilos < 1.0 × 10^9/L; < 0.75 × 10^9/L en los participantes con conocimiento de afectación de médula ósea por la enfermedad maligna
    b) plaquetas < 75 × 10^9/L; < 50 × 10^9/L en los participantes con conocimiento de afectación de médula ósea por la enfermedad maligna
    c) aclaramiento de creatinina < 50 mL/min según la fórmula de Cockcroft-Gault
    - Anomalías clínicamente importantes del metabolismo de la glucosa, como participantes con diabetes mellitus de tipo I o tipo II que precisan insulina y con hemoglobina glucosilada >/= 8.0% (63.9 mmol/mol)
    - Tratamiento previo con cualquiera de los siguientes:
    a) Cualquier agente en investigación o fármaco experimental en un estudio clínico previo, en el plazo de 5 semividas de dicho producto o de las 2 semanas anteriores a la primera dosis del capivasertib en este estudio
    b) Inhibidores o inductores potentes de CYP3A4 y/o UGT2B7, en el plazo de las 2 semanas anteriores a la primera dosis del tratamiento del estudio (3 semanas en el caso del hipérico), o sustratos sensibles de CYP3A4, CYP2C9 y/o CYP2D6 de estrecho margen terapéutico, en el plazo de 1 semana previa a la primera dosis del tratamiento del estudio.
    c) Alotrasplante de células madre hematopoyéticas en el plazo de los 6 meses previos a la primera dosis del capivasertib (serán elegibles los pacientes sometidos a alotrasplante HSCT > 6 meses si no han presentado enfermedad injerto contra el huésped y no están recibiendo tratamiento inmunosupresor concomitante). Tratamientos celulares previos (por ejemplo, tratamiento con células CAR-T) y/o autotrasplante de células madre hematopoyéticas en el plazo de los 3 meses anteriores a la primera dosis del capivasertib.
    d) Recepción de vacuna con gérmenes vivos atenuados en el plazo de los 28 días anteriores a la primera dosis del tratamiento(s) del estudio.
    e) No podrán participar los pacientes que, como consecuencia de otras enfermedades/historia previa/medicamentos concomitantes se encuentrn, en opinión del investigador, en riesgo de tromboembolismo venoso (TEV) y que no desean recibir profilaxis frente al TEV. El inicio de una profilaxis anti-TEV adecuada se basará en la evaluación del riesgo/beneficio por el médico del paciente y en conformidad con las directrices terapéuticas locales.

    Hay también otros criterios de exclusión adicionales; para ello, sírvanse ver el protocolo

    Criterios de exclusión específicos del Módulo 1:
    1. Linfoma folicular de grado 3B.
    2. Conocimiento de transformación a linfoma agresivo, por ejemplo, a linfoma de células grandes.
    3. Paciente con LCM con variante blastoide o polimórfica o con mutación de TP53 documentada a la entrada en el estudio/última recidiva.
    4. Paciente que, en opinión del investigador, va a precisar de forma inmediata tratamiento citorreductor para el control de su enfermedad
    E.5 End points
    E.5.1Primary end point(s)
    Objective response rate is defined as the proportion of patients achieving either complete response or partial response according to the Lugano 2014 Classification for NHL as assessed by blinded independent central review (BICR)
    Tasa de respuesta objetiva, definida como porcentaje de pacientes que alcanzan una respuesta completa o respuesta parcial según la clasificación de Lugano 2014 para el LNH, evaluada por un comité de revisión central independiente desconocedor del tratamiento (blinded independent central review, BICR)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Assessment based on Lugano 2014 Classification:
    Weeks 8, 16, 24, 36, 48, and 60 and thereafter every 24 weeks for FL/MZL and every 12 weeks for
    MCL, or as clinically indicated until radiological progression of disease
    Evaluación basada en la Clasificación de Lugano 2014:
    Semanas 8, 16, 24, 36, 48 y 60; posteriormente, cada 24 semanas en el LF/LZM y cada 12 semanas en el LCM, o según indicación clínica, hasta la progresión radiológica de la enfermedad
    E.5.2Secondary end point(s)
    1. Duration of response is defined as the time from the date of first documented response until date of documented progression according to the Lugano 2014 Classification for NHL as assessed by BICR, or death due to any cause
    2. Progression-free survival is defined as the time from the date of first dose until documented disease progression according to the Lugano 2014 Classification for NHL as assessed by BICR, or death due to any cause
    3.Overall survival is defined as time from the date of first dose until the date of death due to any cause.
    4. Patient-reported disease-related symptoms, functioning and health-related quality of life as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
    5. Patient-reported symptomatic AEs and overall side effect burden as measured by PGI-TT and selected items from PRO CTCAE.
    6. Time to first subsequent therapy or death (TFST) is defined as time from date of first dose until the start date of first subsequent anti-lymphoma therapy after discontinuation of study treatment or death due to any cause
    7. Time to objective response (TTR) is defined as time from date of first dose until the date of first documented objective response per the Lugano 2014 Classification for NHL as assessed by BICR
    8. Safety and tolerability will be evaluated in terms of AEs, vital signs, clinical laboratory and ECGs
    9. Plasma concentration of capivasertib pre-dose and post-dose
    1. Duración de la respuesta, definida como el plazo desde la fecha de la primera respuesta documentada hasta la fecha de progresión documentada de acuerdo con la clasificación de Lugano 2014 para el LNH, evaluada por el BICR, o la muerte por cualquier causa
    2. Supervivencia sin progresión (progression-free survival, PFS), definida como el plazo desde la fecha de la primera dosis hasta la progresión documentada de la enfermedad de acuerdo con la clasificación de Lugano 2014 para el LNH, evaluada por el BICR, o la muerte por cualquier causa
    3. Supervivencia global (overall survival, OS), definida como el plazo desde la fecha de la primera dosis hasta la fecha de la muerte por cualquier causa.
    4. Síntomas de la enfermedad, capacidad funcional y calidad de vida relacionada con la salud percibidos por el paciente determinados por el QLQ-C30 de la EORTC (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30])
    5. Síntomas de acontecimientos adversos y carga general de efectos adversos comunicados por el paciente, en su medición mediante PGI-TT y determinados elementos de los PRO CTCAE.
    6. Tiempo hasta el primer tratamiento posterior o la muerte, que se define como el plazo desde la fecha de la primera dosis hasta la fecha de inicio del primer tratamiento posterior contra el linfoma después de la suspensión del tratamiento del estudio o la muerte por cualquier causa
    7. Tiempo hasta la respuesta objetiva, definido como el plazo desde la fecha de la primera dosis hasta la fecha de la primera respuesta objetiva documentada según la clasificación de Lugano 2014 para el LNH, evaluada por el BICR
    8. Seguridad y tolerabilidad, a evaluar en términos de acontecimientos adversos, constantes vitales, parámetros de laboratorio y ECG.
    9. Concentración plasmática de capivasertib antes de la administración y después de la administración
    E.5.2.1Timepoint(s) of evaluation of this end point
    1, 2, 7: based on Lugano 2014 Class.: Weeks 8, 16, 24, 36, 48, 60 and thereafter every 24 w for FL/MZL and every 12 w for MCL, or as clinically indicated until radiological progression of disease
    3. Patient survival is monitored throughout the study and in FU period
    4. C1D1 and every 4 weeks from C1D1 for the first 24 w and then every 12 w thereafter until 12 w post progression
    5. C1D1, every week from C1D1 for the first 4 weeks, every 4 weeks for the next 8 weeks, and every 12 weeks afterwards until EOT
    6. Monitored during follow up period
    8: AEs, vital signs, clinical laboratory: Every patient visit from screening until EOT; ECG: on screening, C1D1, C2D1, Pre-dose C3D1 and every 12 weeks thereafter or as clinically indicated
    9: C1D1: 1, 2 and 4 h post-dose; C1D8, 15, 22: pre-dose
    1,2,7:Según la Clasificación de Lugano 2014: Semanas 8,16,24,36,48y60, posteriormente,cada 24 semanas en el LF/LZM y cada 12 semanas en el LCM,o según esté clínicamente indicado,hasta la progresión radiológica de la enfermedad
    3.La supervivencia del paciente se observará a lo largo del estudio y durante el periodo de seguimiento
    4.En el C1D1 y cada 4 semanas a partir del C1D1 durante las primeras 24 semanas y,posteriormente, cada 12 semanas hasta 12 semanas después de la progresión
    5.En el C1D1,cada 4 semanas a partir del C1D1 durante las primeras 4 semanas; después, cada 4 semanas durante las siguientes 8 semanas y cada 12 semanas posteriormente,hasta el fin del tratamiento
    6.A supervisar durante el periodo de seguimiento.
    Consulte el protocolo para información más detallada.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    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
    Estudio de diseño modular
    Modular study design
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA14
    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
    Denmark
    France
    Korea, Republic of
    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 is defined as the last visit of the last patient in the study or last scheduled procedure shown in the Schedule of Activities in the relevant Module for the last patient in the study globally.
    Se define como fin del estudio la última visita del último paciente en el estudio o del último procedimiento programado especificado en el Calendario de Actividades del Módulo pertinente en el último paciente del estudio considerado globalmente.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months9
    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: 95
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 177
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 87
    F.4.2.2In the whole clinical trial 272
    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)
    No intervention is planned after the end of the study. However, provisions will be in place for patients still enrolled at the end of the study to continue to receive study treatment if, in the opinion of the investigator, they are continuing to receive benefit from treatment.
    No se ha previsto intervención alguna después del fin del estudio. No obstante, se adoptarán medidas para que los pacientes aún incluidos al término del estudio puedan seguir recibiendo tratamiento del estudio si, en opinión del investigador, continúa beneficiándose del tratamiento.
    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 Decision2021-09-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-27
    P. End of Trial
    P.End of Trial StatusOngoing
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