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   40651   clinical trials with a EudraCT protocol, of which   6635   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:2018-003993-29
    Sponsor's Protocol Code Number:207503
    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:2020-02-28
    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 number2018-003993-29
    A.3Full title of the trial
    DREAMM 7: A Multicenter, Open-Label, Randomized Phase III Study to Evaluate the Efficacy and Safety of the Combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone (B-Vd) Compared with the Combination of Daratumumab, Bortezomib and Dexamethasone (D-Vd) in Participants with Relapsed/Refractory Multiple Myeloma
    DREAMM 7: Estudio de fase III, multicéntrico, abierto y aleatorizado para evaluar la eficacia y la seguridad de la combinación de belantamab mafodotín, bortezomib y dexametasona (B-Vd) en comparación con la combinación de daratumumab, bortezomib y dexametasona (D-Vd) en participantes con mieloma múltiple en recaída o refractario.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase III study of belantamab mafodotin, bortezomib, and dexamethasone (B-Vd) versus daratumumab, bortezomib, and dexamethasone (D-Vd) in participants with relapsed/refractory multiple myeloma
    Estudio de fase III de belantamab mafodotín, bortezomib y dexametasona (B-Vd) frente a daratumumab, bortezomib y dexametasona (D-Vd) en participantes con mieloma múltiple en recaída o refractario.
    A.4.1Sponsor's protocol code number207503
    A.5.4Other Identifiers
    Name:Study acronymNumber:DREAMM 7
    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 SponsorGlaxoSmithKline, S.A.
    B.1.3.4CountrySpain
    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 supportGlaxoSmithKline
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline
    B.5.2Functional name of contact pointCentro de Información
    B.5.3 Address:
    B.5.3.1Street AddressC/Severo Ochoa, 2 (P.T.M.)
    B.5.3.2Town/ cityTres Cantos (Madrid)
    B.5.3.3Post code28760
    B.5.3.4CountrySpain
    B.5.4Telephone number+34 902202700
    B.5.5Fax number+34 918070479
    B.5.6E-mailes-ci@gsk.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1925
    D.3 Description of the IMP
    D.3.1Product namebelantamab mafodotin
    D.3.2Product code GSK2857916
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNbelantamab mafodotin
    D.3.9.2Current sponsor codeGSK2857916
    D.3.9.4EV Substance CodeSUB130430
    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) 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 Yes
    D.3.11.13.1Other medicinal product typeBelantamab mafodotin is a humanized afucosylated, maleimidocaproyl monomethyl auristatin phenylalanine (mcMMAF) conjugated IgG1 antibody
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameDexamethasone
    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 INNDexamethasone
    D.3.9.3Other descriptive nameDexamethasone
    D.3.9.4EV Substance CodeSUB07017MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDexamethasone
    D.3.9.3Other descriptive nameDexamethasone
    D.3.9.4EV Substance CodeSUB07017MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number8
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country 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 namebortezomib
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBORTEZOMIB
    D.3.9.1CAS number 179324-69-7
    D.3.9.4EV Substance CodeSUB20020
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3.5
    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.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameDexamethasone
    D.3.4Pharmaceutical form Solution for injection
    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 INNDexamethasone
    D.3.9.3Other descriptive nameDexamethasone
    D.3.9.4EV Substance CodeSUB07017MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number8
    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: 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.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1153
    D.3 Description of the IMP
    D.3.1Product namedaratumumab
    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 INNDARATUMUMAB
    D.3.9.1CAS number 945721-28-8
    D.3.9.4EV Substance CodeSUB175772
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Relapsed/Refractory Multiple Myeloma
    mieloma múltiple en recaída o refractario.
    E.1.1.1Medical condition in easily understood language
    Multiple Myeloma
    mieloma múltiple
    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 10028228
    E.1.2Term Multiple myeloma
    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 compare the efficacy of belantamab mafodotin in combination with bortezomib and dexamethasone (bor/dex) with that of daratumumab in combination with bor/dex in participants with RRMM
    Comparar la eficacia de belantamab mafodotín en combinación con bortezomib y dexametasona (bor/dex) con la de daratumumab en combinación con bor/dex en participantes con MMRR.
    E.2.2Secondary objectives of the trial
    -To further assess the efficacy of belantamab mafodotin in combination with bor/dex with that of daratumumab in combination with bor/dex in terms of other efficacy outcomes in participants with RRMM
    -To evaluate the safety and tolerability of belantamab mafodotin when administered in combination with bor/dex
    -To further describe the exposure to belantamab mafodotin when administered in combination with bor/dex
    -To assess anti-drug antibodies (ADAs) against belantamab mafodotin
    -To evaluate the safety and tolerability of belantamab mafodotin based on self-reported symptomatic adverse effects when administered in combination with bor/dex
    -To evaluate and compare changes in symptoms and health-related quality of life (HRQOL)
    - Evaluar más a fondo la eficacia de belantamab mafodotín en combinación con bor/dex en comparación con la de daratumumab en combinación con bor/dex en cuanto a otros criterios de valoración de la eficacia en participantes con MMRR.
    - Evaluar la seguridad y la tolerabilidad de belantamab mafodotín cuando se administra en combinación con bor/dex.
    - Definir con mayor precisión la exposición a belantamab mafodotín cuando se administra en combinación con bor/dex.
    - Evaluar la aparición de anticuerpos contra el fármaco (ACF) dirigidos contra belantamab mafodotín.
    - Evaluar la seguridad y la tolerabilidad de belantamab mafodotín cuando se administra en combinación con bor/dex, basándose en las reacciones adversas sintomáticas comunicadas por los pacientes.
    - Evaluar y comparar las variaciones de los síntomas y la calidad de vida relacionada con la salud (CVRS).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Capable of giving signed informed consent as described in Section 10.1.3 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
    2. Male or female, 18 years or older (at the time consent is obtained).
    3. Confirmed diagnosis of multiple myeloma as defined by the IMWG criteria.
    4. Previously treated with at least 1 prior line of multiple myeloma (MM) therapy, and must have documented disease progression during or after their most recent therapy according to the IMWG criteria. Note: induction + autologous stem cell transplant (ASCT) + maintenance is 1 line of therapy
    5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Section 10.6 of the protocol).
    6. Participants with a history of ASCT are eligible for study participation provided the following eligibility criteria are met:
    a. ASCT was >100 days prior to initiating study treatment, and
    b. No active bacterial, viral, or fungal infection(s) present.
    7. Must have at least ONE aspect of measurable disease, defined as one the following:
    a. Urine M-protein excretion ≥200 mg/24h, or
    b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or
    c. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65).
    8. All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0) must be ≤ Grade 1 at the time of enrollment, except for alopecia.
    9. Adequate organ system functions as defined by the laboratory assessments listed in Table 3 of the protocol.
    10. Female Participants:
    Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
    Is not a woman of childbearing potential (WOCBP)
    OR
    Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency (Section 10.3 of the protocol) during the intervention period and for 9 months after the last dose of belantamab mafodotin, and 7 months from the last dose of bortezomib, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
    WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1 and agree to use a highly effective method of contraception during the study and for 9 months after the last dose of belantamab mafodotin, and 7 months from the last dose of bortezomib.
    Additional requirements for pregnancy testing during and after study intervention are provided in Section 10.3 and the Schedule of Activities (SoA) of the protocol.
    The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
    11. Male Participants:
    Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    Male participants are eligible to participate if they agree to the following from the time of first dose of study until 6 months after the last dose of belantamab mafodotin, and 4 months from the last dose of bortezomib, to allow for clearance of any altered sperm:
    Refrain from donating sperm
    PLUS either:
    Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
    OR
    Must agree to use contraception/barrier as detailed below:
    Agree to use a male condom, even if they have undergone a successful vasectomy and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as described in Section 10.3 of the protocol when having sexual intercourse with a WOCBP (including pregnant females).
    1. Capaces de dar el consentimiento informado firmado como se indica en la sección 10.1.3 del Protocolo, lo que incluye el cumplimiento de los requisitos y restricciones enumerados en el documento de consentimiento informado (DCI) y en este protocolo.
    2. Varón o mujer mayor de 18 años (en el momento de obtener el consentimiento informado).
    3. Diagnóstico confirmado de mieloma múltiple según lo definido por los criterios del IMWG.
    4. Tratamiento previo con al menos una línea previa de tratamiento del MM y progresión documentada de la enfermedad durante o después del tratamiento más reciente según los criterios del IMWG. Nota: inducción + TAPH + mantenimiento es una línea de tratamiento
    5. Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 a 2 (sección 10.6 del Protocolo).
    6. Los participantes con antecedentes de transplante autólogo TAPH podrán ser incluidos en el estudio siempre que cumplan los siguientes criterios de elegibilidad:
    a. El TAPH se realizó >100 días antes de iniciar el tratamiento del estudio y
    b. Ausencia de infecciones bacterianas, virales o fúngicas activas.
    7. Presencia de al menos UN aspecto de enfermedad medible, definido como uno de los siguientes:
    a. Excreción urinaria de proteína M ≥200 mg/24 h
    b. Concentración sérica de proteína M ≥0,5 g/dl (≥5,0 g/l)
    c. Análisis de cadenas ligeras libres (CLL) en suero: concentración de CLL afectadas ≥10 mg/dl (≥ 100 mg/l) y cociente anormal de cadenas ligeras libres en suero (< 0,26 o >1,65).
    8. Todos los efectos tóxicos relacionados con el tratamiento previo (definidos por los Criterios de toxicidad comunes para acontecimientos adversos del National Cancer Institute [NCI-CTCAE] v5.0) deben ser de grado ≤1 en el momento de la inclusión, excepto la alopecia.
    9. Función orgánica adecuada, definida por las evaluaciones analíticas que se presentan en la Tabla 3 del Protocolo
    10. Mujeres participantes:
    El uso de anticonceptivos por las mujeres debe cumplir las normas locales referentes a los métodos anticonceptivos utilizados por participantes en estudios clínicos.
    Las mujeres podrán participar si no están embarazadas ni en periodo de lactancia y si se cumple al menos una de las condiciones siguientes:
    No es una mujer en edad fértil (MEF)
    O
    Es una MEF y utiliza un método anticonceptivo muy eficaz (con un índice de fallos <1% anual), preferiblemente con una baja dependencia de la usuaria (sección 10.3), durante el período de intervención y durante 9 meses después de la última dosis de belantamab mafodotín y 7 meses después de la última dosis de bortezomib, y se compromete a no donar óvulos (ovocitos) con fines reproductivos durante este período. El investigador deberá evaluar la eficacia del método anticonceptivo en relación con la primera dosis de la intervención del estudio.
    Las MEF deberán dar negativo en una prueba de embarazo en suero muy sensible en las 72 horas previas a la administración del D1C1 y comprometerse a utilizar un método anticonceptivo muy eficaz durante el estudio y durante 9 meses después de la última dosis de belantamab mafodotín y 7 meses después de la última dosis de bortezomib.
    En la sección 10.3 del Protocoloy en el calendario de actividades se indican otros requisitos para las pruebas de embarazo durante y después de la intervención del estudio.
    El investigador es responsable de revisar los antecedentes médicos, los antecedentes menstruales y la actividad sexual reciente para reducir el riesgo de inclusión de una mujer con un embarazo de poco tiempo no detectado.
    11. Varones participantes:
    El uso de anticonceptivos por los varones debe cumplir las normas locales referentes a los métodos anticonceptivos utilizados por participantes en estudios clínicos.
    Los varones podrán participar si se comprometen a todo lo siguiente desde el momento de la primera dosis del tratamiento del estudio hasta 6 meses después de la última dosis de belantamab mafodotín y 4 meses después de la última dosis de bortezomib para permitir que desaparezca cualquier alteración del esperma:
    Abstenerse de donar semen,
    MÁS:
    Abstinencia de relaciones heterosexuales como modo de vida habitual y preferido (abstinencia a largo plazo y persistente) y compromiso de mantenerla.
    O
    Compromiso de utilizar métodos anticonceptivos/de barrera tal como se detalla a continuación:
    Compromiso de utilizar preservativo masculino, aunque se haya sometido a una vasectomía eficaz, y de que la pareja femenina utilice otro método anticonceptivo muy eficaz con un índice de fallos < 1 % anual, descritos en la sección 10.3 del Protocolo, cuando mantenga relaciones sexuales con una MEF (incluso si está embarazada).
    E.4Principal exclusion criteria
    1. Intolerant to daratumumab.
    2. Refractory to daratumumab or any other anti-CD38 therapy (defined as progressive disease during treatment with anti-CD38 therapy, or within 60 days of completing that treatment).
    3. Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m2 twice weekly, or within 60 days of completing that treatment). Note: participants with progressive disease during treatment with a weekly bortezomib regimen are allowed.
    4. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain.
    5. Prior treatment with anti-BCMA therapy.
    6. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter.
    7. Plasmapheresis within 7 days prior to the first dose of study drug.
    8. Has received radiotherapy to a large pelvic area (check with sponsor). Bridging radiotherapy otherwise is allowed. NOTE: Disease assessment should be repeated if RT is done prior to first dose of study drug within screening window.
    9. Prior allogenic stem cell transplant. NOTE – Participants who have undergone syngeneic transplant will be allowed, only if no history of GvHD.
    10. Any major surgery within 4 weeks prior to the first dose of study drug. Exception allowed for bone stabilizing surgery after consultation with medical monitor.
    11. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil criteria given in Table 3 of the protocol.
    12. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures.
    13. Evidence of active mucosal or internal bleeding.
    14. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
    15. Previous or concurrent malignancies other than multiple myeloma, unless the second malignancy has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. NOTE: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.
    16. Evidence of cardiovascular risk including any of the following:
    a. Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including second degree (Mobitz Type II) or third degree atrioventricular (AV) block.
    b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.
    c. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Section 10.8 of the protocol).
    d. Uncontrolled hypertension.
    17. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, daratumumab, bortezomib, boron or mannitol or any other components of the study treatment.
    18. Active infection requiring treatment.
    19. Known HIV infection.
    20. Presence of hepatitis B surface antigen (HbsAg), or hepatitis B core antibody (HbcAb), at screening or within 3 months prior to first dose of study treatment. Note: presence of Hep B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant.
    21. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
    NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
    22. Current corneal epithelial disease except for mild punctuate keratopathy (Section 10.9 of the protocol).
    23. Intolerance or contraindications to anti-viral prophylaxis.
    24. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes) or active plasma cell leukaemia at the time of screening.
    1. Intolerancia a daratumumab.
    2. Resistencia a daratumumab u otro anti-CD38 (se define como progresión durante el tratamiento anti-CD38 o en los 60 días siguientes al la finalización).
    3. Intolerancia a bortezomib o resistencia a bortezomib (lo que se define como progresión durante el tratamiento con una pauta con bortezomib de 1,3 mg/m2 dos veces por semana o en los 60 días siguientes a la finalización). Nota: se permite progresión de la enfermedad durante el tratamiento con una pauta semanal de bortezomib.
    4. Neuropatía periférica o dolor neuropático de grado 2 o superior en curso.
    5. Tratamiento previo con anti-BCMA.
    6. Tratamiento previo con un anticuerpo monoclonal en los 30 días previos a la administración de la primera dosis de los fármacos del estudio o tratamiento con un fármaco en investigación o una terapia sistémica aprobada contra el mieloma (incluidos los esteroides sistémicos) en los 14 días o el equivalente a 5 semividas previos a la administración de la primera dosis de los fármacos del estudio, lo que suponga menos tiempo.
    7. Plasmaféresis en los 7 días previos a la primera dosis del fármaco del estudio.
    8. Administración de radioterapia en una zona pélvica extensa (comprobar con el promotor). Por lo demás, se permite la radioterapia transitoria. NOTA: La evaluación de la enfermedad deberá repetirse si se administra radioterapia antes de la primera dosis del fármaco del estudio dentro del margen de selección.
    9. Trasplante alogénico de progenitores hepatopoyéticos previo. NOTA – Los participantes que se hayan sometido a un trasplante singénico solo podrán ser incluidos si no tienen antecedentes de EICH.
    10. Cualquier intervención de cirugía mayor en las 4 semanas previas a la primera dosis del fármaco del estudio. Se permite una excepción para la cirugía de estabilización ósea previa consulta con el monitor médico.
    11. Enfermedad renal activa (infección, necesidad de diálisis o cualquier otro trastorno que pueda afectar a la seguridad del participante). Podrán participar pacientes con proteinuria aislada debida al MM, siempre que cumplan los criterios indicados en la Tabla 3.
    12. Cualquier trastorno médico, psiquiátrico o de otro tipo grave o inestable (incluidas anomalías analíticas) que pueda interferir en la seguridad del participante, la obtención del consentimiento informado o el cumplimiento de los procedimientos del estudio.
    13. Signos de hemorragia activa de mucosas o interna.
    14. Cirrosis o enfermedad hepática o biliar inestable actual conforme a la evaluación del investigador, definida por la presencia de ascitis, encefalopatía, coagulopatía, hipoalbuminemia, varices esofágicas o gástricas, o ictericia persistente. NOTA: Es aceptable una enfermedad hepática no cirrótica crónica estable (como síndrome de Gilbert o litiasis biliar asintomática) si el participante cumple los demás criterios de participación.
    15. Neoplasias malignas previas o concomitantes distintas del mieloma múltiple, a menos que la segunda neoplasia maligna se haya considerado médicamente estable durante al menos 2 años. El participante no podrá estar recibiendo tratamiento activo, aparte de terapia hormonal, para esta enfermedad. NOTA: se permite la participación de pacientes con cáncer de piel distinto del melanoma tratado con intención curativa sin la restricción de 2 años.
    16. Signos de riesgo cardiovascular:
    a. Arritmias actuales clínicamente significativas no tratadas, incluidas anomalías clínicamente significativas en el ECG como bloqueo auriculoventricular (AV) de segundo grado (tipo Mobitz II) o de tercer grado.
    b. Antecedentes de infarto de miocardio, síndromes coronarios agudos (incluida angina de pecho inestable), angioplastia coronaria o implantación de endoprótesis (stent) o injerto de derivación en los tres meses previos a la selección.
    c. Insuficiencia cardíaca de clase III o IV según el sistema de clasificación funcional de la NYHA (sección 10.8 del Protocolo).
    d. Hipertensión no controlada.
    17. Reacción de hipersensibilidad inmediata o diferida o reacción idiosincrásica conocidas a fármacos relacionados químicamente con belantamab mafodotín, daratumumab, bortezomib, boro o manitol, o con cualquier otro componente del tratamiento del estudio.
    18. Infección activa con necesidad de tratamiento.
    19. Infección conocida por el VIH.
    20. Presencia de antígeno de superficie del virus de la hepatitis B (HBsAg) o de anticuerpos anti-HBc en el momento de selección o en los tres meses previos a la primera dosis del estudio. Nota: anticuerpos contra el antígeno de superficie del virus de la hepatitis B (HBsAb) que indiquen una vacunación previa no será motivo de exclusión.
    21. Resultado positivo de anticuerpos contra virus de la hepatitis C o en el análisis de ARN del virus de la hepatitis C en la selección o en los tres meses previos a la primera dosis del estudio.
    (Ver Protocolo para una lista completa de los criterios de exclusión.)
    E.5 End points
    E.5.1Primary end point(s)
    Progression-Free Survival (PFS), defined as the time from the date of randomization until the earliest date of documented disease progression or death due to any cause
    Supervivencia sin progresión (SSP), definida como el tiempo transcurrido entre la fecha de la aleatorización y la fecha más temprana de progresión de la enfermedad o la muerte por cualquier causa.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to approximately 34 months from the time when the first participant is randomized (progression-free survival final analysis)
    Hasta aproximadamente 34 meses desde el momento de la aleatorización del primer paciente (análisis final de la supervivencia sin progresión).
    E.5.2Secondary end point(s)
    -Complete Response Rate (CRR), defined as the percentage of participants with a confirmed complete response (CR) or better (i.e., CR, stringent complete response (sCR))
    -Overall Response Rate (ORR), defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, VGPR, CR, sCR)
    -Duration of Response (DoR), defined as the time from first documented evidence of PR or better until progressive disease (PD) or death due to PD among participants who achieve confirmed PR or better
    -Time to Response (TTR), defined as the time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better
    -Time to Progression (TTP), defined as the time from the date of randomization until the earliest date of documented PD or death due to PD
    -Overall Survival (OS), defined as the time from the date of randomization until the date of death due to any cause
    -PFS2, defined as time from randomization to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever is earlier. If disease progression after new anti-cancer therapy cannot be measured, a PFS event is defined as the date of discontinuation of new anti-cancer therapy, or death from any cause, whichever is earlier
    -Minimal Residual Disease (MRD) negativity rate, defined as the percentage of participants who are MRD negative by next-generation sequencing (NGS)
    - Incidence of adverse events (AEs) and changes in laboratory parameters
    - Ocular findings on ophthalmic exam
    - Plasma concentrations of belantamab mafodotin, total monoclonal antibody (mAb), and cys-mcMMAF
    - Incidence and titers of anti-drug antibodies (ADAs) against belantamab mafodotin
    - Changes from baseline in symptoms and related impacts as measured by PRO-CTCAE
    - Change from baseline in HRQOL as measured by EORTC QLQ-C30 and EORTC IL52 (disease symptoms domain from the EORTC QLQ-MY20)
    - Tasa de respuesta completa (TRC), definida como el porcentaje de participantes con una respuesta completa (RC) o mejor confirmada [es decir, RC, respuesta completa estricta (RCe)].
    - Tasa de respuesta global (TRG), definida como el porcentaje de participantes con una respuesta parcial (RP) o mejor (es decir, RP, RPMB, RC, RCe) confirmada.
    - Duración de la respuesta (DR), definida como el tiempo transcurrido entre el primer signo documentado de RP o mejor y la progresión de la enfermedad (PE) o la muerte por PE en los participantes que logren una RP o mejor confirmada.
    - Tiempo hasta la respuesta (THR), definido como el tiempo transcurrido entre la fecha de aleatorización y el primer signo documentado de respuesta (RP o mejor) en los participantes que logren una RP o mejor confirmada.
    - Tiempo hasta la progresión (THP), definido como el tiempo transcurrido entre la fecha de aleatorización y la fecha más temprana de PE documentada o muerte por PE.
    - Supervivencia global (SG), definida como el tiempo transcurrido entre la fecha de aleatorización y la fecha de la muerte por cualquier causa.
    - SSP2, definida como el tiempo transcurrido entre la aleatorización y la progresión de la enfermedad tras el comienzo de un nuevo tratamiento antineoplásico o la muerte por cualquier causa, lo que ocurra antes. Si no puede medirse la progresión de la enfermedad después de un nuevo tratamiento antineoplásico, un episodio de SSP se define como la fecha de suspensión del nuevo tratamiento antineoplásico o la muerte por cualquier causa, lo que ocurra antes.
    - Tasa de negatividad para enfermedad residual mínima (ERM), definida como el porcentaje de participantes con ERM negativa mediante secuenciación de última generación (SUG).
    - Incidencia de acontecimientos adversos (AA) y variaciones de los parámetros analíticos.
    - Hallazgos oculares en la exploración oftalmológica.
    - Concentraciones plasmáticas de belantamab mafodotín, anticuerpo monoclonal (AcM) total y cys-mcMMAF.
    - Incidencia y títulos de ACF dirigidos contra belantamab mafodotín.
    - Variaciones con respecto al momento basal de los síntomas y sus efectos relacionados, determinados mediante PRO-CTCAE.
    - Variación con respecto al momento basal de la CVRS determinada mediante los cuestionarios QLQ-C30 e IL52 de la EORTC (dominio de síntomas de la enfermedad del cuestionario QLQ-MY20 de la EORTC).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Up to approximately 74 months (at completion of the study) from the time when the first participant is randomized for all secondary endpoints
    Hasta aproximadamente 74 meses (a la finalización del estudio) desde el momento de la aleatorización del primer paciente para todas las variables secundarias.
    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 Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    tolerability
    tolerabilidad
    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 Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the 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 concerned13
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA72
    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
    Belgium
    Brazil
    Canada
    China
    Czech Republic
    France
    Germany
    Greece
    Israel
    Italy
    Japan
    Korea, Republic of
    Mexico
    Netherlands
    New Zealand
    Poland
    Russian Federation
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of study is defined as 5 years from Last Participant First Visit (LSFV), or when all participants have died, withdrawn consent, or have been lost to follow-up, whichever occurs first.
    El final del estudio se define como 5 años desde la última visita del último paciente, o cuando todos los participantes hayan fallecido, retirado el consentimiento o se hayan perdido para el seguimiento, lo que ocurra antes.
    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 months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 239
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 239
    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 state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 203
    F.4.2.2In the whole clinical trial 478
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    There is no planned provision of study intervention following the end of the study.
    The Investigator is responsible for ensuring that consideration has been given to the poststudy care of the participant's medical condition.
    No está previsto ninguna intervención más después del final del estudio. El investigador es responsable de garantizar que se haya considerado la asistencia médica del paciente tras el estudio.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-05-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-13
    P. End of Trial
    P.End of Trial StatusOngoing
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA