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    Summary
    EudraCT Number:2021-000043-49
    Sponsor's Protocol Code Number:LOXO-BTK-20022
    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:2021-07-08
    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 number2021-000043-49
    A.3Full title of the trial
    A Phase 3 Open-Label, Randomized Study of Fixed Duration Pirtobrutinib (LOXO-305) plus Venetoclax and Rituximab versus Venetoclax and Rituximab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-322)
    Estudio en fase III, abierto y aleatorizado de pirtobrutinib de duración determinada (LOXO 305) con venetoclax más rituximab frente a venetoclax más rituximab en pacientes con leucemia linfocítica crónica o linfoma linfocítico de células pequeñas (BRUIN CLL-322) previamente tratados
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Trial of Fixed Duration Pirtobrutinib (LOXO-305) plus Venetoclax and Rituximab versus Venetoclax and Rituximab in Previously Treated CLL/SLL
    Ensayo en fase III de pirtobrutinib de duración determinada (LOXO 305) con venetoclax más rituximab frente a venetoclax más rituximab en pacientes con LLC / LLCP previamente tratados
    A.4.1Sponsor's protocol code numberLOXO-BTK-20022
    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 SponsorLoxo Oncology 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 supportLoxo Oncology Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIQVIA RDS GmbH
    B.5.2Functional name of contact pointMedical and Scientific Services
    B.5.3 Address:
    B.5.3.1Street AddressUnterschweinstiege 2-14.
    B.5.3.2Town/ cityFrankfurt am Main
    B.5.3.3Post code60549
    B.5.3.4CountryGermany
    B.5.4Telephone number+34916635000
    B.5.6E-mailmarialeticia.solari@iqvia.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 namePirtobrutinib
    D.3.2Product code LOXO-305
    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 INNPirtobrutinib
    D.3.9.1CAS number 2101700-15-4
    D.3.9.2Current sponsor codeLOXO-305
    D.3.9.3Other descriptive nameLY3527727
    D.3.9.4EV Substance CodeSUB215610
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 namePirtobrutinib
    D.3.2Product code LOXO-305
    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 INNPirtobrutinib
    D.3.9.1CAS number 2101700-15-4
    D.3.9.2Current sponsor codeLOXO-305
    D.3.9.3Other descriptive nameLY3527727
    D.3.9.4EV Substance CodeSUB215610
    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: 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.3.1Product namePirtobrutinib
    D.3.2Product code LOXO-305
    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 INNPirtobrutinib
    D.3.9.1CAS number 2101700-15-4
    D.3.9.2Current sponsor codeLOXO-305
    D.3.9.4EV Substance CodeSUB215610
    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: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name MabThera
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRituximab
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product 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: 5
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name MabThera
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Pharma (Switzerland) AG, Basel
    D.2.1.2Country which granted the Marketing AuthorisationSwitzerland
    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 nameRituximab
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product 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: 6
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Venclyxto
    D.2.1.1.2Name of the Marketing Authorisation holderAbbVie Deutschland GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameVenclyxto
    D.3.4Pharmaceutical form 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 INNVENETOCLAX
    D.3.9.1CAS number 1257044-40-8
    D.3.9.4EV Substance CodeSUB176260
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration 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.IMP: 7
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Venclyxto
    D.2.1.1.2Name of the Marketing Authorisation holderAbbVie Deutschland GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameVenclyxto
    D.3.4Pharmaceutical form 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 INNVENETOCLAX
    D.3.9.1CAS number 1257044-40-8
    D.3.9.4EV Substance CodeSUB176260
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
    leucemia linfocítica crónica / linfoma linfocítico de células pequeñas
    E.1.1.1Medical condition in easily understood language
    Chronic lymphocytic leukaemia/Small Lymphocytic Lymphoma is a type of cancer that affects the white blood cells and tends to progress slowly over many years.
    leucemia linfocítica crónica / linfoma linfocítico de células pequeñas es un tipo de cáncer que afecta a los glóbulos blancos y tiende a progresar lentamente durante muchos años.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10008976
    E.1.2Term Chronic lymphocytic leukemia
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To evaluate PFS of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B)
    • Evaluar (SSP) de pirtobrutinib más venetoclax y rituximab (grupo A) en comparación con venetoclax y rituximab (grupo B)
    E.2.2Secondary objectives of the trial
    • To evaluate the effectiveness of Arm A compared to Arm B based on overall response rate (ORR) and time to event(s) outcomes
    • To evaluate the safety and tolerability of each treatment arm
    • To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms and physical functioning
    • Evaluar la efectividad del grupo A en comparación con el grupo B con base en la tasa de respuesta global (TRG) y el tiempo hasta el resultado del (los) acontecimiento(s)
    • Evaluar la seguridad y la tolerabilidad de cada grupo de tratamiento
    • Evaluar la efectividad del grupo A en comparación con el grupo B en los síntomas relacionados con la enfermedad notificados por el paciente y el funcionamiento físico
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 18 and older at time of enrollment.
    Type of Patient and Disease Characteristics
    2. Confirmed diagnosis by redacted local laboratory report of CLL/SLL as defined by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria including the following:
    a) B-cells coexpressing the surface antigen CD5 together with at least one B-cell antigen (CD19, CD20, CD23) and either κ or λ light-chain restricted (for CLL/SLL patients).
    b) ≥ 5 × 109 B lymphocytes/L (5000/μL) in the peripheral blood (for CLL patients).
    c) Prolymphocytes may comprise ≤ 55% of blood lymphocytes (for CLL patients).
    3. A requirement for therapy consistent with iwCLL 2018 criteria for initiation of therapy such that at least 1 of the following should be met:
    a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (such as hemoglobin < 10 g/dL) and/or thrombocytopenia (such as platelets ≤ 100 × 109/L).
    b) Massive (i.e., spleen edge ≥ 6 cm below the left costal margin) or progressive or symptomatic splenomegaly (> 13 cm).
    c) Massive nodes (i.e., ≥ 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
    d) Progressive lymphocytosis with an increase of > 50% over a 2-month period, or lymphocyte doubling time < 6 months. Factors contributing to lymphocytosis other than CLL/SLL (e.g., infections, steroid administration) should be excluded.
    e) Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids.
    f) Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, spine).
    g) Disease-related symptoms (also known as B-symptoms) as defined by any of the following:
    i. Unintentional weight loss ≥ 10% within the previous 6 months.
    ii. Significant fatigue (i.e., Eastern Cooperative Oncology Group performance status [ECOG PS] 2 or worse; cannot work or unable to perform usual activities).
    iii. Fevers ≥ 100.5°F or 38.0°C for 2 or more weeks without evidence of infection.
    iv. Night sweats for ≥ 1 month without evidence of infection.
    4. Known 17p deletion status as indicated in Section 1.2.2.
    5. Previously treated with at least one line of therapy that may include a covalent BTK inhibitor (patients may be eligible if they have previously received a covalent BTK inhibitor or if they have not previously received a covalent BTK inhibitor). There is no limit on prior number of lines of therapy.
    6. Eastern Cooperative Oncology Group (ECOG) 0-2.
    7. Must have adequate organ function, as defined in the protocol. These values must be met during the Screening Period as well as pre-dose on C1D1 (see table).
    8. Patients who have received investigational agents, anticancer treatment and/or radiotherapy are required the have the following washout periods prior to planned C1D1:
    a) Targeted agents: 5 half-lives or 14 days, whichever is shorter
    b) Cytotoxic chemotherapy: 28 days
    c) Therapeutic monoclonal antibodies: 28 days
    d) Palliative limited field radiation: 7 days
    e) Broad field radiation (≥ 30% of bone marrow or whole brain radiotherapy): 28 days
    9. Prior treatment related AEs must have recovered to Grade ≤ 1 or pretreatment baseline with the exception of alopecia
    Contraception
    10. Willingness of men and women of childbearing potential (WOCBP), and their partners, to both observe highly effective birth control methods as outlined in Section 10.2 (Appendix 2; and below) for the duration of treatment and for 6 months following the last dose of study treatment or 12 months after the last dose of rituximab, whichever is later.
    When pirtobrutinib is taken with hormonal contraceptives (e.g., birth control pills), pirtobrutinib might affect the birth control. More effective birth control, such as using 2 birth control methods should be considered.
    WOCBP are defined as those women following menarche, and who are not postmenopausal (or 2 years of non-therapy-induced amenorrhea, or surgically sterile). WOCBP must utilize highly effective contraception methods as outlined below. In addition, male partners must use a barrier method (condoms) for the duration of treatment and for 6 months following the last dose of study treatment or 12 months after the last dose of rituximab, whichever is later. Male patients with partners who are WOCBP must use a barrier method (condoms) and their partner must also use a highly effective form of contraception as listed below for the duration of treatment and for 6 months following the last dose of study treatment or 12 months after the last dose of rituximab, whichever is later.
    Please refer to Protocol
    1.Tener ≥18 años en la inscripción.
    Tipo paciente y características enfermedad
    2.Diagnóstico confirmado mediante informe por escrito del lab local de LLC/LLCP definido según siguientes criterios del Taller internacional sobre la leucemia linfocítica crónica (iwCLL) 2018:
    a)Linfocitos B que coexpresan el antígeno de superficie CD5 junto con, al menos,un antígeno de linfocitos B (CD19,CD20,CD23) y restringidos a la cadena ligera o (pacientes con LLC/LLCP)
    b)≥5 × 109 linfocitos B/l (5000/μl) en sangre periférica(para pacientes con LLC)
    c)prolinfocitos pueden comprender ≤55 % de linfocitos sanguíneos (pacientes con LLC)
    3.Necesidad de tratamiento en consonancia con los criterios del iwCLL 2018 para el inicio del tratamiento,de modo que se cumpla al menos 1 de los siguientes criterios:
    a)Indicios de insuficiencia medular progresiva, manifestada por el desarrollo de anemia(ej, hemoglobina <10 g/dl) o trombocitopenia (ejemplo,plaquetas ≤100 × 109/l),o el agravamiento de las mismas
    b)Bazo masivo (margen del bazo a ≥6 cm por debajo del margen costal izquierdo) o esplenomegalia progresiva o sintomática (>13 cm)
    c)Ganglios masivos (≥10 cm en su diámetro mayor) o linfadenopatía progresiva o sintomática
    d)Linfocitosis progresiva con un incremento de >50 % durante un periodo 2 meses o un tiempo de duplicación de linfocitos <6 meses. Deben excluirse los factores que contribuyen a la linfocitosis distintos de la LLC/LLCP (ej.,infecciones, administración de esteroides)
    e)Complicaciones autoinmunitarias,incluida la anemia o la trombocitopenia que responden mal a los corticoesteroides
    f)Afectación extraganglionar sintomática o funcional (ej. piel riñón,pulmón,columna vertebral)
    g)Síntomas relacionados con la enfermedad (también conocidos como síntomas B) definidos por cualquiera de los siguientes:
    i.Pérdida de peso involuntaria ≥10 % en los últimos 6 meses
    ii.Cansancio significativo (ej,estado funcional del Grupo Oncológico Cooperativo del Este [ECOG PS] de 2 o peor; no puede trabajar o no puede realizar las actividades habituales)
    iii.Fiebre ≥100,5 °F o 38,0 °C durante 2 o más semanas sin signos de infección
    iv.Sudores nocturnos durante ≥1 mes sin signos de infección
    4.Eliminación comprobada de 17p como se indica en el apartado 1.2.2
    5.Pacientes tratados previamente con al menos una línea de tratamiento que pueda incluir un inhibidor covalente de BTK (los pacientes pueden ser aptos si han recibido previamente un inhibidor covalente de BTK o si no lo han recibido).No existe límite en cuanto al número anterior de líneas de tratamiento
    6.Grupo Oncológico Cooperativo del Este (ECOG) de 0-2
    7.Debe presentar una función orgánica adecuada, según se define a continuación. Estos valores deberán cumplirse durante el periodo de selección, así como antes de la dosis el D1C1. (tabla)
    8.Es necesario que los pacientes que hayan recibido fármacos en investigación, antineoplásicos o radioterapia realicen los siguientes periodos de reposo farmacológico antes del D1C1 previsto:
    a)Fármacos selectivos:5 semividas o 14 d, lo que sea más corto
    b)Quimioterapia citotóxica: 8d
    c)Anticuerpos monoclonales terapéuticos:28d
    d)Radioterapia paliativa de campo limitado:7d
    e)Radioterapia de campo extendido (≥30 % médula ósea o radioterapia en todo el cerebro):28d
    9.Los AA relacionados con el tratamiento previo deben haberse recuperado hasta grado ≤1 o valores iniciales previos al tratamiento, con la excepción alopecia
    Anticoncepción
    10.Voluntad de los hombres y las mujeres en edad fértil (MEF) y sus parejas, emplear métodos anticonceptivos de alta eficacia, como se describen en el apartado10.2 (Anexo 2; y a continuación) durante el tratamiento y durante 6 meses después de la última dosis del tratamiento del estudio o 12 meses después de la última dosis de rituximab, lo que sea más tarde
    Cuando el pirtobrutinib se toma con anticonceptivos hormonales (ej, píldora anticonceptiva), podría afectar al método anticonceptivo.Se debe considerar un método anticonceptivo más eficaz, tal como el uso de 2 métodos anticonceptivos
    Las MEF se definen como las mujeres después de la menarquia y que no se encuentran en periodo posmenopáusico (o tras 2 años de amenorrea no inducida por fármacos o quirúrgicamente estériles) Las MEF deben utilizar métodos anticonceptivos de alta eficacia, como se indica a continuación.Además, las parejas masculinas deben usar un método de barrera (preservativos) durante el tratamiento y hasta 6 meses después de la última dosis del tratamiento del estudio o 12 meses después de la última dosis de rituximab, lo que ocurra más tarde. Los pacientes varones con parejas femeninas en edad fértil deben usar un método de barrera (preservativo) y su pareja también debe usar un método anticonceptivo altamente eficaz, como se indica a continuación, durante el tratamiento y hasta 6 meses después última dosis del tratamiento del estudio o 12 meses después última dosis de rituximab, lo que ocurra más tarde.Referirse Protocolo
    E.4Principal exclusion criteria
    1. Known or suspected Richter’s Transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin lymphoma at any time preceding enrollment.
    2. Known or suspected history of central nervous system (CNS) involvement by CLL/SLL.
    3. History of Grade ≥2 arrhythmia on prior covalent BTK inhibitor.
    4. Patients who experienced a major bleeding event on a prior BTK inhibitor.
    NOTE: Major bleeding is defined as bleeding having one or more of the following features: life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2 g/dL; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome).
    5. Active second malignancy. Patients with treated second malignancy who are in remission with life expectancy > 2 years and with documented Sponsor approval are eligible. Examples include:
    a) Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease.
    b) Adequately treated cervical carcinoma in situ without current evidence of disease.
    c) Localized (e.g., lymph node negative) breast cancer treated with curative intent with no evidence of active disease present for more than 3 years and receiving adjuvant hormonal therapy.
    d) Localized prostate cancer undergoing active surveillance.
    e) History of treated and cured Hodgkin's disease or NHL < 5 years from diagnosis.
    6. Major surgery within 4 weeks of planned start of study therapy.
    7. A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic, that, in the opinion of the Investigator, would adversely affect the patient’s participation in this study or interpretation of study outcomes.
    8. History of allogeneic or autologous SCT or CAR-T therapy within the past 60 days.
    9. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) not on a stable regimen and dose for at least 4 weeks prior to study enrollment.
    10. Significant cardiovascular disease, defined as any of the following:
    a) Unstable angina or acute coronary syndrome within the past 2 months
    b) History of myocardial infarction within 3 months prior to planned start of study treatment
    c) Documented left ventricular ejection fraction (LVEF) by any method of ≤ 40% in the 12 months prior to planned start of study treatment
    d) ≥ Grade 3 New York Heart Association (NYHA) functional classification system of heart failure, uncontrolled or symptomatic arrhythmias
    11. Prolongation of the QT interval corrected (QTc) for heart rate using Fredericia’s Formula (QTcF) > 470 msec on at least 2 of 3 consecutive electrocardiograms (ECGs), and mean QTcF > 470 msec on all 3 ECGs, during Screening.
    a) QTcF is calculated using Fredericia’s Formula (QTcF = QT/(RR^0.33)
    b) Correction of suspected drug-induced QTcF prolongation or prolongation due to electrolyte abnormalities can be attempted at the Investigator’s discretion, and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation or electrolyte supplementation.
    c) Correction of QTc for underlying bundle branch block (BBB) permissible.
    12. Hepatitis B or hepatitis C testing indicating active/ongoing infection based on screening laboratory tests as defined as:
    a) Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before randomization. Patients who are hepatitis B PCR positive will be excluded.
    b) Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA positive will be excluded.
    13. Known active cytomegalovirus (CMV) infection. Unknown or negative status eligible.
    14. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal) or other clinically significant
    active disease process which in the opinion of the Investigator and Medical Monitor may pose a risk for patient participation. Screening for chronic conditions is not required.
    15. Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count. Patients with unknown or negative status are eligible.
    16. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the oral administered study treatments.
    Please refer to Protocol
    1.Sospecha de,o confirmación de transformación de Richter a (LDLBG),leucemia prolinfocítica o linfoma de Hodgkin en cualquier momento antes de la inscripción
    2.Sospecha de,o confirmación de antecedentes de afectación del SNC por LLC/LLCP
    3.Antecedentes de arritmia de grado ≥2 durante el tto anterior con el inhibidor covalente de BTK
    4.Pacientes que experimentaron un episodio hemorrágico grave con un inhibidor de la BTK anterior
    NOTA:episodio hemorrágico grave se define como una hemorragia que presenta una o más de las siguientes características:hemorragia potencialmente mortal con signos o síntomas de afectación hemodinámica;hemorragia asociada con una disminución del nivel de hemoglobina de al menos 2 g/dl;o bien,hemorragia en un área u órgano crítico
    5.Segunda neoplasia maligna activa. Son aptos los pacientes con una segunda neoplasia maligna tratada que estén en remisión con una esperanza de vida >2 años y con la autorización documentada del promotor. Entre los ejemplos se incluyen:
    a)Cáncer de piel no melanomatoso adecuadamente tratado o melanoma sobre lentigo maligno sin indicios actuales de enfermedad
    b)Carcinoma cervicouterino in situ tratado adecuadamente y sin indicios actuales de enfermedad
    c)Cáncer de mama localizado tratado con intención curativa sin indicios de enfermedad activa presente durante más de 3 años y que reciba tratamiento hormonal complementario
    d)Cáncer de próstata localizado sometido a vigilancia activa
    e)Antecedentes de enfermedad de Hodgkin o LNH tratados y curados <5 años desde el diagnóstico
    6.Cirugía mayor en las 4 semanas anteriores al inicio previsto del tratamiento del estudio
    7.Antecedentes importantes de afecciones renales,neurológicas,psiquiátricas,endocrinas, metabólicas o inmunitarias que,a criterio del investigador,podrían afectar de forma negativa a la participación del paciente en este estudio o a la interpretación de los resultados del estudio.
    8.Antecedentes de tratamiento con SCT o CAR-T alogénicas o autólogas en los últimos 60 días
    9.Citopenia autoinmunitaria activa no controlada
    10.Enfermedad cardiovascular importante, definida como cualquiera de los siguientes:
    a)Angina inestable o síndr. coronario agudo en los últimos 2 meses
    b)Antecedentes de infarto de miocardio en los 3 meses anteriores al inicio previsto del tto del estudio
    c)Fracción de expulsión del ventrículo izquierdo (FEVI) documentada mediante cualquier método ≤40 % en los 12 meses anteriores al inicio previsto del tratamiento del estudio
    d)Insuficiencia cardíaca de grado ≥3 según el sistema de clasificación funcional de la NYHA, arritmias no controladas o sintomáticas
    11.Prolongación del intervalo QTc para la QTcF >470 ms en al menos 2 de 3 ECG)consecutivos y QTcF medio >470 ms en los 3 ECG durante la selección.
    a)El QTcF se calcula mediante la fórmula de Fredericia (QTcF = QT/(RR^0,33)
    b)Se puede intentar corregir la prolongación de QTcF inducida por fármacos o la prolongación inducida por anomalías electrolíticas, según el criterio del investigador y solo si es clínicamente seguro hacerlo mediante la interrupción del fármaco causante o el cambio a otro fármaco sin asociación documentada con la prolongación del QTcF o el suplemento de electrolitos
    c)permite la corrección del QTc para el hemibloqueo ventricular (HV) subyacente.
    12.Pruebas de hepatitis B o C que indican una infección activa/en curso en función de las pruebas analíticas de la selección, definidas como:
    a)VHB: se excluyen aquellos pacientes con resultado positivo para el HBsAg. Los pacientes con presencia de anticuerpos contra el anti-HBc y negativo para el HbsAg requieren evaluación mediante PCR para la hep B antes de la aleatorización. Se excluirá a los pacientes con resultados + para la hep B mediante PCR
    b)VHC: presencia de anticuerpos contra la hep C.En caso de que haya presencia de anticuerpos contra la hep C, será necesario que no haya en el paciente presencia de ARN)del virus de la hep C antes de la aleatorización. Se excluirá a aquellos pacientes con resultado + para el ARN del virus de la hep C.
    13.Infección activa conocida por CMV. Son aptos los pacientes en situación desconocida o negativa.
    14.Indicios de otras afecciones clínicamente significativas no controladas, entre las que se incluyen, pero sin limitarse a estas, infección diseminada incontrolada (vírica, bacteriana o fúngica) u otros procesos patológicos activos clínicamente representativos que según el criterio del investigador y del supervisor médico, puedan suponer un riesgo para la participación de los pacientes. No necesario un proceso de identificación para las enfermedades crónicas.
    15.Infección por el virus de VIH comprobada, independientemente del recuento de CD4. Son aptos los pacientes en situación desconocida o negativa.
    16.Sínd. de malabsorción activo clínicamente importante u otra enfermedad que pueda afectar a la GI de los tratamientos del estudio administrados por vía oral.
    Referirse al Protocolo
    E.5 End points
    E.5.1Primary end point(s)
    PFS per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018, assessed by Independent Review Committee (IRC)
    • SSP según los criterios de 2018 del Taller Internacional sobre Leucemia Linfocítica Crónica (iwCLL), según la evaluación del Comité de Revisión Independiente (CRI)
    E.5.1.1Timepoint(s) of evaluation of this end point
    The time from the date of randomization until disease progression or death from any cause, whichever occurs first.
    el tiempo transcurrido desde la fecha de aleatorización hasta la fecha de la progresión de la enfermedad o muerte por cualquier causa, lo que ocurra primero.
    E.5.2Secondary end point(s)
    • Assessed by Investigator:
    - Progression free survival (PFS)
    - Overall survival (OS)
    - Time to next treatment (TTNT), defined as time from the date of randomization to the date of the next non-protocol-specified therapy for CLL/SLL (Section 9.4.4 for full definition).
    - Event free survival (EFS) defined as the time from date of randomization to the date of disease progression (PD) or start of new treatment for CLL/SLL or discontinuation from trial due to toxicity or death, whichever occurs first.
    • Assessed by Investigator and IRC:
    - ORR
    • Including but not limited to SAEs, AEs, deaths and clinical laboratory abnormalities per National Cancer Institute Common Terminology Criteria in Adverse Events version 5.0 (NCI CTCAE v5.0)
    • Time to worsening (TTW) of CLL/SLL-related symptoms
    • TTW of physical functioning
    Evaluado por el investigador:
    - Supervivencai sin progresión (SSP)
    - Supervivencia general (SG)
    - Tiempo hasta el siguiente tratamiento (TST), definido como el tiempo transcurrido desde la fecha de aleatorización hasta la fecha del siguiente tratamiento no especificado en el protocolo para la LLC/el LLCP (ver Sección 9.4.4 para la definición completa)
    - Supervivencia libre de acontecimientos (SLA) definida como el tiempo transcurrido desde la fecha de aleatorización hasta la fecha de la progresión de la enfermedad (PE) o el inicio de un nuevo tratamiento para la LLC/el LLCP o la interrupción del ensayo debido a toxicidad o muerte, lo que ocurra primero.
    • Evaluado por el investigador y el CRI:
    - TRG
    • Incluidos, entre otros, acontecimientos adversos graves (AAG), acontecimientos adversos (AA), muertes y anomalías analíticas clínicas según los criterios terminológicos comunes para acontecimientos adversos del Instituto Nacional del Cáncer de los EE. UU., versión 5.0 (NCI CTCAE v5.0)
    • Tiempo hasta el empeoramiento (ThE) de los síntomas relacionados con la LLC/el LLCP
    • ThE del funcionamiento físico
    E.5.2.1Timepoint(s) of evaluation of this end point
    PFS - The time from the date of randomization until disease progression or death from any cause, whichever occurs first.
    ORR - The number of patients who achieve a best overall response (BOR) of CR, CRi, nPR, or partial remission (PR) divided by the total number of patients randomized to each treatment arm.
    OS- The time from randomization until death from any cause.
    TTNT - Time from the date of randomization to the date of the initiation of the next non-protocol-specified therapy for CLL/SLL or death from any cause, whichever occurred first.
    EFS - The time from date of randomization to the date of disease progression or start of new treatment for CLL/SLL or withdrawal from study due to toxicity or death, whichever occurs first.
    SSP-tiempo transcurrido desde fecha de aleatorización hasta fecha de progresión de enfermedad o muerte por cualquier causa,lo que ocurra primero
    TRG-nº de pacientes que logran una mejor respuesta global de RC, RCi, nPR o remisión parcial dividido por el número total de pacientes asignados al azar a cada brazo de tto
    SG-tiempo transcurrido desde aleatorización hasta muerte por cualquier causa
    TNT-Tiempo transcurrido desde fecha de aleatorización hasta fecha de inicio del siguiente tto no especificado en protocolo para LLC/LLCP o muerte por cualquier causa,lo que ocurra primero
    EFS-Tiempo transcurrido desde fecha de aleatorización hasta fecha de progresión de enfermedad o el inicio de un nuevo tto para LLC/LLCP o retirada de estudio debido a toxicidad o muerte,lo que ocurra primero
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA56
    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
    China
    Israel
    Japan
    Korea, Republic of
    Russian Federation
    Singapore
    Taiwan
    United States
    Belgium
    Denmark
    France
    Germany
    Hungary
    Ireland
    Italy
    Netherlands
    Norway
    Poland
    Spain
    Sweden
    Switzerland
    United Kingdom
    Czechia
    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 end of the study is defined as the date of the last visit of the last participant in the study or last scheduled procedure shown in the Schedule of Assessments (SoA) for the last participant in the trial globally, which is estimated at approximately 60 months from the first patient randomized to allow approximately 17 months recruitment and 43 months of follow-up (i.e., at least 3.5 years follow up for all enrolled patients).
    El final del estudio se define como la fecha de la última visita del último participante en el estudio o del último procedimiento programado que figura en el Calendario de Evaluaciones (SoA) para el último participante en el ensayo de forma global, que se estima en aproximadamente 60 meses desde el primer paciente aleatorizado para permitir aproximadamente 17 meses de reclutamiento y 43 meses de seguimiento (es decir, al menos 3,5 años de seguimiento para todos los pacientes inscritos).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    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 years5
    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: 180
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 420
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 226
    F.4.2.2In the whole clinical trial 600
    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)
    Arms A and B are time-limited regimens and treatment is considered complete when patients complete treatment cycles
    The Sponsor reserves the right to discontinue the study for clinical or administrative reasons at any time.
    Los brazos A y B son regímenes de tiempo limitado y el tratamiento se considera completo cuando los pacientes completan los ciclos de tratamiento
    El Promotor se reserva el derecho de interrumpir el estudio por razones clínicas o administrativas en cualquier momento.
    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 Decision2021-08-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-08-18
    P. End of Trial
    P.End of Trial StatusOngoing
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