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   36060   clinical trials with a EudraCT protocol, of which   5926   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:2017-001468-39
    Sponsor's Protocol Code Number:GS-US-313-1090
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-04-17
    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 number2017-001468-39
    A.3Full title of the trial
    Phase 1b trial evaluating idelalisib in children and adolescents with relapsed or refractory diffuse large B-cell lymphoma or mediastinal B-cell lymphoma in combination with RICE
    Ensayo en fase Ib para evaluar idelalisib en niños y adolescentes con linfoma difuso de células B grandes o linfoma mediastínico de células B recidivante o resistente en combinación con RICE
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 1b trial evaluating idelalisib in children and adolescents with relapsed or refractory diffuse large B-cell lymphoma or mediastinal B-cell lymphoma in combination with RICE
    Ensayo en fase Ib para evaluar idelalisib en niños y adolescentes con linfoma difuso de células B grandes o linfoma mediastínico de células B recidivante o resistente en combinación con RICE
    A.4.1Sponsor's protocol code numberGS-US-313-1090
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/018/2017
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGilead Sciences, 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 supportGilead Sciences, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGilead Sciences International Ltd.
    B.5.2Functional name of contact pointClinical Trial Mailbox
    B.5.3 Address:
    B.5.3.1Street AddressFlowers Building, Granta Park
    B.5.3.2Town/ cityAbington, Cambridge
    B.5.3.3Post codeCB21 6GT
    B.5.3.4CountryUnited Kingdom
    B.5.5Fax number+441223897284
    B.5.6E-mailclinical.trials@gilead.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 Yes
    D.2.1.1.1Trade name Zydelig 100 mg film-coated tablet
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences International Ltd
    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.3.2Product code IDELA, GS-1101
    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 INNIDELALISIB
    D.3.9.1CAS number 870281-82-6
    D.3.9.2Current sponsor codeGS-1101
    D.3.9.3Other descriptive nameIDELA
    D.3.9.4EV Substance CodeSUB126168
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Zydelig 150 mg film-coated tablet
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences International Ltd
    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.3.2Product code IDELA, GS-1101
    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 INNIDELALISIB
    D.3.9.1CAS number 870281-82-6
    D.3.9.2Current sponsor codeGS-1101
    D.3.9.3Other descriptive nameIDELA
    D.3.9.4EV Substance CodeSUB126168
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation 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.3.2Product code IDELA, GS-1101
    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 INNIDELALISIB
    D.3.9.1CAS number 870281-82-6
    D.3.9.2Current sponsor codeGS-1101
    D.3.9.3Other descriptive nameIDELA
    D.3.9.4EV Substance CodeSUB126168
    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: 4
    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.3.2Product code IDELA, GS-1101
    D.3.4Pharmaceutical form Dispersible tablet
    D.3.4.1Specific paediatric formulation Yes
    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 INNIDELALISIB
    D.3.9.1CAS number 870281-82-6
    D.3.9.2Current sponsor codeGS-1101
    D.3.9.3Other descriptive nameIDELA
    D.3.9.4EV Substance CodeSUB126168
    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 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    B-cell malignancies
    Neoplasias de células B
    E.1.1.1Medical condition in easily understood language
    B-cell malignancies
    Neoplasias de células B
    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 10036714
    E.1.2Term Primary mediastinal large B-cell lymphoma refractory
    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 10012822
    E.1.2Term Diffuse large B-cell lymphoma refractory
    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
    - Evaluate safety, tolerability, and pharmacokinetics (PK) of idelalisib during an initial 3-week course of idelalisib monotherapy in pediatric subjects 1 to less than 18 years of age with relapsed or refractory DLBCL or MBCL
    - Establish the safety, tolerability, and preliminary efficacy (complete response (CR)/partial response (PR) utilizing the International Pediatric Non-Hodgkin Lymphoma Response Criteria of idelalisib monotherapy and idelalisib in combination with RICE (rituximab, ifosfamide, carboplatin and etoposide) chemoimmunotherapy
    - Establish recommended Phase 2 doses of idelalisib in combination with RICE
    Evaluar la seguridad, la tolerabilidad y la farmacocinética (FC) de idelalisib durante un ciclo inicial de 3 semanas de idelalisib en monoterapia en sujetos pediátricos de 1 a menos de 18 años de edad con LDCBG o LMCB recidivante o resistente.
    • Evaluar la seguridad, la tolerabilidad y la eficacia preliminar (respuesta completa [RC]/respuesta parcial [RP] utilizando los criterios internacionales de respuesta en el linfoma no Hodgkin pediátrico {Sandlund 2015}) de idelalisib en monoterapia y de idelalisib en combinación con la quimioinmunoterapia de rescate RICE (rituximab, ifosfamida, carboplatino y etopósido).
    • Establecer las dosis recomendadas para la fase 2 (DRF2) de idelalisib en combinación con RICE.
    E.2.2Secondary objectives of the trial
    - Evaluate the PK of idelalisib during combination therapy
    - Perform exploratory biomarker analyses during idelalisib monotherapy
    - Evaluate palatability and acceptability of idelalisib 10-mg dispersible tablets in pediatric subjects
    • Evaluar la FC de idelalisib durante la politerapia.
    • Realizar análisis de biomarcadores exploratorios durante la monoterapia con idelalisib.
    • Evaluar la palatabilidad y la aceptabilidad de los comprimidos dispersables de 10 mg idelalisib en sujetos pediátricos.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Male or female subjects 1 to less than 18 years of age
    2) Histologically confirmed diagnosis of DLBCL, or MBCL established by the World Health Organization 2008 classification of tumors of hematopoietic and lymphoid tissues
    3) Relapsed or refractory DLBCL or MBCL
    a) Refractory disease is defined as a < 50% decrease in lesion size with first-line therapy.
    b) Relapsed reflects progressive disease or the appearance of new lesions after attainment of complete or partial remission.
    c) Subjects who fail first line therapy may be categorized into 3 distinct groups: those who relapsed after complete remission, partial response with persistent disease and refractory.
    4) Measurable or evaluable disease based on imaging, bone marrow examination.
    5) Karnofsky ≥ 60% for patients > 16 years of age or Lansky ≥ 60 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
    6) A negative serum pregnancy test is required for female subjects of child bearing potential.
    7) Male subjects and female subjects of child bearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 5 of the protocol.
    8) Lactating females must agree to discontinue nursing before idelalisib is administered
    9) Adequate bone marrow function defined as:
    a) For subjects without bone marrow involvement:
    o Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL, in the absence of growth factors
    o Platelet count ≥ 100,000/μL (transfusion independent)
    o Hemoglobin ≥ 8.0 gm/dL (RBC transfusion independent)
    b) For subjects with bone marrow involvement (requires BM documentation):
    o Platelet count ≥ 20,000/μL (may receive platelet transfusions or thrombopoietic growth factors)
    o Hemoglobin ≥ 8.0 gm/dL (may receive RBC transfusions or erythropoietic growth factors)
    10) Adequate renal function defined as: Estimated creatinine clearance (CrCL) ≥ 70 mL/min/1.73m2 (using the Schwartz formula; =k x L/sCr) ([k is proportionality constant: for children 1-12 years old or adolescent females ≥ 12 years old, k=0.55, and for adolescent males ≥ 12 years old, k=0.70]; L is height in centimeters [cm]; and sCr is serum creatinine [mg/dL])
    11) Parent/legal guardian must provide written informed consent prior to screening evaluations. Subject will provide assent/consent if applicable.
    1) Sujetos de ambos sexos de 1 año a menos de 18 años de edad.
    2) Diagnóstico histológicamente confirmado de LDCBG o LMCB, establecido según la clasificación de tumores de tejido hematopoyético y linfoide de 2008 de la Organización Mundial de la Salud.
    3) LDCBG o LMCB recidivante o resistente
    a) La enfermedad resistente se define como una disminución <50% en el tamaño de la lesión con terapia de primera línea.
    b) Recidivante refleja la enfermedad progresiva o la aparición de nuevas lesiones después de lograr la remisión completa o parcial.
    c) Los sujetos que fracasan en la terapia de primera línea pueden clasificarse en 3 grupos distintos: los que recidivaron después de la remisión completa, los con respuesta parcial a la enfermedad resistente y los con enfermedad resistente .
    4) Enfermedad mensurable o evaluable mediante estudios de imagen o mielograma.
    5) Puntuación de Karnofsky ≥ 60% para pacientes > 16 años de edad o puntuación de Lansky ≥ 60 para pacientes ≤ 16 años de edad. Los pacientes que no puedan caminar debido a parálisis pero que vayan en silla de ruedas se considerarán ambulatorios a efectos de evaluación de la escala funcional.
    6) En las pacientes con capacidad de concebir, se requiere una prueba de embarazo en suero con resultado negativo.
    7) Los varones y las mujeres con capacidad de concebir que mantengan relaciones heterosexuales deberán comprometerse a usar uno o más métodos anticonceptivos especificados en el protocolo, según se describe en el Apéndice 5.
    8) Las mujeres en período de lactancia deberán comprometerse a dejar de amamantar antes de la administración de idelalisib.
    9) Función medular adecuada de la médula ósea, definida como:
    a) En sujetos sin afectación de la médula ósea:
    o Recuento absoluto de neutrófilos (RAN) en sangre periférica ≥ 1000/μl, en ausencia de factores de crecimiento
    o Recuento de plaquetas ≥ 100 000/μl (independiente de transfusión)
    o Hemoglobina ≥ 8,0 g/dl (independiente de transfusión de eritrocitos)
    b) En sujetos con afectación de la médula ósea (se requiere documentación de la MO):
    o Recuento de plaquetas ≥ 20 000/μl (puede recibir transfusiones de plaquetas o factores de crecimiento trombopoyéticos)
    o Hemoglobina ≥ 8,0 g/dl (puede recibir transfusiones de eritrocitos o factores de crecimiento eritropoyéticos)
    10) Función renal adecuada, definida como: Aclaramiento de creatinina calculado (CrCL) ≥ 70 ml/min/1,73 m2 (usando la fórmula de Schwartz; = k x L/sCr)
    ([k es la constante de proporcionalidad: en niños/as de 1-12 años o chicas adolescentes ≥ 12 años, k = 0,55, y en chicos adolescentes ≥ 12 años k = 0,70]; L es la estatura en centímetros [cm]; y sCr es la creatinina sérica [mg/dl])
    11) El progenitor/tutor legal debe proporcionar el consentimiento informado por escrito antes de las evaluaciones de selección. Si procede, el sujeto dará su asentimiento/consentimiento.
    E.4Principal exclusion criteria
    1) Subjects previously treated with ICE, with or without an anti-CD20 antibody, or history of hypersensitivity to any components of RICE
    2) Known active central nervous system or leptomeningeal lymphoma
    3) Active infection with HIV, HBV, HCV or CMV based on screening serology and PCR results
    4) Evidence of uncontrolled systemic bacterial, fungal, or viral infection at the time of treatment start (Day 1)
    5) Ongoing or history of drug-induced pneumonitis
    6) Ongoing or history of inflammatory bowel disease
    7) Pregnancy or breastfeeding
    8) Currently receiving other anti-cancer agents or other investigational drug
    9) Prior solid organ transplantation
    10) Prior allogeneic stem cell transplantation within 60 days or active acute graft versus host disease (GVHD) grade 3 or higher (see Appendix 6 for GVHD grading)
    11) Known hypersensitivity to idelalisib, the metabolites, or formulation excipients.
    12) Urinary outflow obstruction or inflammation of the urinary bladder
    (cystitis)
    1) Sujetos tratados previamente con ICE, con o sin un anticuerpo anti-CD20, o antecedentes de hipersensibilidad a cualquiera de los componentes de RICE.
    2) Afectación activa conocida del sistema nervioso central por el linfoma, incluida afectación leptomeníngea.
    3) Infección activa por VIH, CMV, VHB o VHC según los resultados serológicos y de PCR de la selección.
    4) Indicios de infección sistémica bacteriana, fúngica o vírica en el momento del inicio del tratamiento (día 1).
    5) Presencia o antecedentes de neumonitis inducida por fármacos.
    6) Presencia o antecedentes de enfermedad inflamatoria intestinal.
    7) Embarazo o lactancia.
    8) El sujeto recibe actualmente otro antineoplásico u otro fármaco en investigación.
    9) Trasplante de órgano sólido previo.
    10)Alotrasplante de células madre en los 60 días previos o enfermedad de injerto contra huésped (EICH) aguda activa de grado 3 o mayor (véase la gradación de la EICH en el Apéndice 6).
    11)Hipersensibilidad conocida al idelalisib, sus metabolitos o los excipientes de su formulación.
    12) Obstrucción del flujo urinario o inflamación de la vejiga urinaria
    (cistitis)
    E.5 End points
    E.5.1Primary end point(s)
    - Incidence rate of Dose Limiting Toxicities (DLTs)
    - Overall safety profile of idelalisib as measured by the incidence of AEs, serious AEs (SAEs), AEs leading to idelalisib interruption, idelalisib dose reduction, premature discontinuation of idelalisib, or death
    - Tasa de incidencia de toxicidad limitante de la dosis (TLD)
    - Perfil de seguridad global de idelalisib medido por la incidencia de acontecimientos adversos (AA), acontecimientos adversos graves (AAG), acontecimientos adversos que conducen a la interrupción de idelalisib, reducción de dosis de idelalisib, interrupción prematura de idelalisib o muerte.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Subjects will be seen in the clinic at least once per week during Weeks 1 through 4. Subsequent visits will occur at least every 3 weeks through EOS. Subjects will be assessed for safety at each visit. Subjects will be assessed for disease status by continuous utilization of a single modality including CT or MRI at screening, at Day 21 (or earlier if there is evidence of clinical progression), and up to 1 week prior to Day 1 of Cycles 3, 5, 8, 11, and 14 to evaluate response to study treatment. EOS imaging will be done only if imaging was not performed within 9 weeks of the EOS visit. Subjects with bone marrow involvement at baseline will require marrow evaluation at each response assessment time point.
    Los sujetos acudirán a visitas al centro al menos 1vez a la semana durante las semanas 1 a 4.Posteriormente,las visitas serán al menos cada 3 semanas hasta la visita de FDE. Se evaluará la seguridad de los sujetos en todas las visitas. Se evaluará el estado de la enfermedad mediante el uso continuado de 1única modalidad como TC o RM en la selección, el día 21 o antes si hay indicios de progresión clínica y hasta 1 semana antes del día 1 de los ciclos 3, 5, 8, 11 y14 para evaluar la respuesta al tratamiento del estudio. Se hará 1estudio de imagen en la visita de FDE solo si no se ha realizado ya uno en las 9semanas previas a tal visita.En los sujetos con afectación de médula ósea en el momento basal se requerirá 1evaluación de la médula ósea en cada momento de evaluación de la respuesta.
    E.5.2Secondary end point(s)
    - Rate of Grade ≥ 3 transaminase elevations based on laboratory findings
    - Overall response rate (ORR) – defined as the proportion of subjects who achieve a best response of Complete Response (CR) or Partial Response (PR) after the first dose of idelalisib (either as a result of monotherapy or in combination with RICE chemoimmunotherapy). The screening imaging study will serve as the reference for ORR.
    - Overall Survival (OS) – defined as the interval from the first dose date of idelalisib to death from any cause.
    - Progression-Free Survival (PFS) – defined as the interval from the start date of RICE to the earlier of the first documentation of disease progression or death from any cause. CT/MRI scan at the conclusion of idelalisib monotherapy will serve as the reference for progression.
    - Pharmacokinetic parameters (Cmax, Ctrough and AUC) for idelalisib and metabolite GS-563117
    - Optional exploratory biomarkers (eg pAKT, pS6 ribosomal protein) on bone marrow samples at baseline and Day 21, for subjects with marrow involvement at baseline
    - Acceptability and palatability of idelalisib 10-mg dispersible tablet at Day 1 of idelalisib monotherapy and at Day 1, Cycle 1 of idelalisib in combination with RICE chemoimmunotherapy
    - Tasa de Grado ≥ 3 elevaciones de transaminasas en base a los hallazgos de laboratorio
    Tasa de respuesta global (TRG): se define como la proporción de sujetos que logran una mejor respuesta de respuesta completa (RC) o respuesta parcial (RP) después de la primera dosis de idelalisib (como resultado de monoterapia o en combinación con quimioinmunoterapia con RICE) . El estudio de imaginología de detección servirá como referencia para TRG.
    - Supervivencia global (SG): se define como el intervalo desde la fecha de la primera dosis de idelalisib hasta la muerte por cualquier causa.
    - Supervivencia sin progresión (SSP): se define como el intervalo desde la fecha de inicio de RICE hasta la primera documentación inicial de la progresión de la enfermedad o muerte por cualquier causa. La tomografía computarizada / MRI al final de la monoterapia con idelalisib servirá como referencia para la progresión.
    - Parámetros farmacocinéticos (Cmax, Ctrough y AUC) para idelalisib y metabolito GS-563117
    - Biomarcadores exploratorios opcionales (p. Ej., PAKT, proteína ribosomal pS6) en muestras de médula ósea al inicio del estudio y el día 21, para sujetos con afectación medular al inicio del estudio
    - Aceptabilidad y palatabilidad de la tableta dispersable de 10 mg de idelalisib en el día 1 de monoterapia con idelalisib y en el día 1, ciclo 1 de idelalisib en combinación con quimioinmunoterapia con RICE
    E.5.2.1Timepoint(s) of evaluation of this end point
    Subjects will be seen in the clinic at least once per week during Weeks 1 through 4. Subsequent visits will occur at least every 3 weeks through EOS. Subjects will be assessed for safety at each visit. Subjects will be assessed for disease status by continuous utilization of a single modality including CT or MRI at screening, at Day 21 (or earlier if there is evidence of clinical progression), and up to 1 week prior to Day 1 of Cycles 3, 5, 8, 11, and 14 to evaluate response to study treatment. EOS imaging will be done only if imaging was not performed within 9 weeks of the EOS visit. Subjects with bone marrow involvement at baseline will require marrow evaluation at each response assessment time point.
    Los sujetos acudirán a visitas al centro al menos 1vez a la semana durante las semanas 1 a 4.Posteriormente,las visitas serán al menos cada 3 semanas hasta la visita de FDE. Se evaluará la seguridad de los sujetos en todas las visitas. Se evaluará el estado de la enfermedad mediante el uso continuado de 1única modalidad como TC o RM en la selección, el día 21 o antes si hay indicios de progresión clínica y hasta 1 semana antes del día 1 de los ciclos 3, 5, 8, 11 y14 para evaluar la respuesta al tratamiento del estudio. Se hará 1estudio de imagen en la visita de FDE solo si no se ha realizado ya uno en las 9semanas previas a tal visita. En los sujetos con afectación de médula ósea en el momento basal se requerirá 1evaluación de la médula ósea en cada momento de evaluación de la respuesta.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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
    Paediatric study to investigate safety in children
    E.7.2Therapeutic exploratory (Phase II) No
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    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
    Czech Republic
    France
    Germany
    Italy
    New Zealand
    Poland
    Spain
    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
    For each subject, end-of-study assessments will be completed once it has been determined that the subject will discontinue all study assessments. Survival follow-up will be conducted annually for a period of 5 years. The end of the study is defined when the last subject reaches the last scheduled follow-up time point, is lost to follow-up, withdraws from the study, dies or the time at which the sponsor closes the study.
    Para cada sujeto, las evaluaciones de fin de estudio se completará una vez que se ha determinado que el sujeto se interrumpirá todas las evaluaciones del estudio. El seguimiento de supervivencia se realizará anualmente por un período de 5 años. El final del estudio se define cuando el último sujeto alcanza el último punto programado de seguimiento, se pierde el seguimiento, se retira del estudio, fallece, o cuando el promotor cierra el estudio.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 36
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 6
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 15
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 15
    F.1.2Adults (18-64 years) No
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Each subject’s parents or legal guardian must sign and date the most recent IRB/IEC-approved informed consent form before any study procedures are performed. Each study subject will also sign an Assent Form, as required by IRB/IEC/local requirements.
    Los padres o tutores legales de cada sujeto deben firmar y fechar el FCI más reciente aprobado por CEIm antes de realizar cualquier procedimiento de estudio.Cada sujeto del estudio también firmará un FA,según lo requerido por CEIm/requisitos locales.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state21
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 60
    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)
    After withdrawal from the study, medical treatment of the subject is left to the investigator’s discretion.
    Después de la retirada del estudio, el tratamiento médico del sujeto se deja a discreción del investigador.
    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 Decision2018-04-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-04-03
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2018-11-16
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA