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    Summary
    EudraCT Number:2010-024215-14
    Sponsor's Protocol Code Number:C25001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-04-26
    Trial results View 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 number2010-024215-14
    A.3Full title of the trial
    A Randomized, Open-Label, Phase 3 Trial of brentuximab vedotin (SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T-Cell Lymphoma
    Estudio en fase 3, abierto, aleatorizado con brentuximab vedotin (SGN-35) frente al tratamiento de elección del investigador (metotrexato o bexaroteno) en pacientes con linfoma cutáneo de células T CD30 positivo
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of Bretuximab Vedotin Compared to Physician's Choice in Patients With CD30-Positive Cutaneous T-Cell Lymphoma
    Estudio de Bretuximab Vedotin comparado con tratamiento elegido por el investigador en pacientes con linfoma cutáneo de células T CD30 positivo
    A.4.1Sponsor's protocol code numberC25001
    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 SponsorMillennium Pharmaceuticals, 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 supportMillennium Pharmaceuticals, Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMillennium, Drug Information Call Centre
    B.5.2Functional name of contact pointDrug Information Call Centre
    B.5.3 Address:
    B.5.3.1Street Address40 Landsdowne Street
    B.5.3.2Town/ cityCambridge, Massachssetts
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number+115107402412
    B.5.5Fax number+118008816092
    B.5.6E-mailmedical@mlnm.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/3/11/939
    D.3 Description of the IMP
    D.3.1Product nameBrentuximab vedotin
    D.3.2Product code SGN-35
    D.3.4Pharmaceutical form Powder for 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 INNBrentuximab vedotin
    D.3.9.1CAS number 914088-09-8
    D.3.9.2Current sponsor codeSGN-35
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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.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.2.1.1.1Trade name Methotrexate
    D.2.1.1.2Name of the Marketing Authorisation holderGoldshield Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical 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 INNMETHOTREXATE
    D.3.9.1CAS number 59-05-2
    D.3.9.4EV Substance CodeSUB08856MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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: 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.2.1.1.1Trade name Targretin
    D.2.1.1.2Name of the Marketing Authorisation holderEisai Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Capsule, soft
    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 INNBEXAROTENE
    D.3.9.1CAS number 153559-49-0
    D.3.9.4EV Substance CodeSUB00795MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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
    CD30-Positive Cutaneous T-Cell Lymphoma
    linfoma cutáneo de células T CD30 positivo
    E.1.1.1Medical condition in easily understood language
    A type of cancer of the immune system requiring treatment.
    Tipo de cáncer del sistema inmunológico que requiere tratamiento.
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10011677
    E.1.2Term Cutaneous T-cell lymphoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine ORR, lasting at least 4 months, with brentuximab
    vedotin in patients with CD30+ MF or pcALCL compared to that achieved with therapy in the control arm
    Determinar la tasa de respuesta global (TRG), de 4 meses de duración como mínimo, asociada a brentuximab vedotin en pacientes con MF o LACGcp CD30+, en comparación con la lograda con el tratamiento en el grupo de control.
    E.2.2Secondary objectives of the trial
    CR rate with brentuximab vedotin compared to that achieved with
    therapy in the control arm
    Determinar la tasa de respuesta completa (RC) con brentuximab vedotin en comparación con la lograda con el tratamiento en el grupo de control.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Voluntary consent form
    - Male or female patients 18 years or older with diagnosis of MF or pcALCL
    - Histologically confirmed CD30+ disease by central laboratory
    assessment and pathology review
    - Eastern Cooperative Oncology Group (ECOG) performance status ?2
    - Female patients who are post menopausal, surgically sterile,
    or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
    - Male patients who agree to practice effective barrier
    contraception or agree to abstain from heterosexual intercourse
    - Clinical laboratory value as specified in protocol
    - Consentimiento Voluntario
    - Pacientes de uno u otro sexo con una edad mínima de 18 años y diagnóstico de MF o de LACGcp.
    - Enfermedad CD30+ confirmada histológicamente por la evaluación del laboratorio central y la revisión anatomopatológica.
    - Estado funcional del Eastern Cooperative Oncology Group (ECOG) ? 2 (véase el apartado 15.1).
    - Mujeres que son posmenopáusicas durante al menos un año antes de la visita de selección o son estériles por motivos quirúrgicos, o si están en edad fértil, se comprometen a emplear dos métodos anticonceptivos eficaces al mismo tiempo, desde el momento en que se firme el consentimiento informado y hasta 30 días después de la última dosis del medicamento del estudio o se comprometen a abstenerse completamente de mantener relaciones heterosexuales.
    - Varones, aun cuando estén esterilizados quirúrgicamente que se comprometen a emplear un método anticonceptivo de barrera eficaz durante todo el período de tratamiento del estudio y hasta 6 meses después de la última dosis del medicamento del estudio, o se comprometen a abstenerse completamente de mantener relaciones heterosexuales.
    - Valores analíticos que se especifican en el protocolo
    E.4Principal exclusion criteria
    - A concurrent diagnosis of systemic ALCL, other non Hodgkin
    lymphoma(excluding LyP) or Sezary syndrome
    - Patients with cardiovascular conditions specified in protocols
    - Patients with history of another primary malignancy not in
    remission for at least 3 years
    - Known active cerebral/meningeal disease, HIV infection, hepatitis B or Hepatitis C infection
    - Oral retinoid therapy for any indication within 12 weeks of
    study entry
    - Corticosteroid therapy within 4 weeks or immunosuppressive
    chemotherapy or any immunotherapy within 12 weeks of
    first dose of study drug
    - Female patients who are lactating or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on
    - Diagnóstico simultáneo de LACG sistémico u otro linfoma no hodgkiniano (a excepción de LACGcp) o síndrome de Sézary.
    - Cualquiera de las enfermedades cardiovasculares especificadas en el protocolo
    - Antecedentes de otra neoplasia maligna primaria que no ha estado en remisión durante al menos 3 años.
    - Enfermedad cerebral/meníngea activa conocida, incluidos signos o síntomas de leucoencefalopatía multifocal progresiva (LMP).
    - Infección por el VIH conocida.
    - Hepatitis B con antígeno de superficie positivo conocida, o bien hepatitis C activa conocida o sospechada.
    - Cualquier infección sistémica viral, bacteriana o micótica activa que requiera tratamiento antimicrobiano sistémico en las 2 semanas anteriores a la primera dosis de medicamento del estudio.
    - Recepción de quimioterapia inmunodepresora o de cualquier tipo de inmunoterapia (por ejemplo, reposición de inmunoglobulinas u otros tratamientos con anticuerpos monoclonales) en las 12 semanas anteriores a la primera dosis de medicamento del estudio.
    - Tratamiento con corticoides en las 4 semanas anteriores a la primera dosis de medicamento del estudio.
    - Hipersensibilidad conocida a proteínas recombinantes, a proteínas murinas o a alguno de los excipientes contenidos en la formulación del medicamento.
    - Mujeres que estén en período de lactancia o que tengan una prueba de embarazo en suero positiva durante el período de selección o una prueba de embarazo en orina positiva el día 1 de cualquier ciclo.
    - Tratamiento con radioterapia o con cualquier producto en investigación en los 21 días anteriores a la primera dosis de medicamento del estudio.
    - Progresión durante el tratamiento previo con bexaroteno y metotrexato.
    - Tratamiento con retinoides orales por cualquier indicación en las 12 semanas anteriores a la incorporación al estudio.
    - Tratamiento sistémico con vitamina A en dosis superiores a 15.000 UI (5000 µg) al día (equivalente a aproximadamente 3 veces el aporte diario recomendado) en los 30 días anteriores a la primera dosis de medicamento del estudio.
    - Antecedentes de pancreatitis o factores de riesgo importantes de pancreatitis.
    E.5 End points
    E.5.1Primary end point(s)
    To determine the proportion of patients achieving an objective response that lasts at least 4 months
    Determinar la proporción de pacientes que logren una respesta objetiva de 4 meses de duración como mínimo según el CRI
    E.5.1.1Timepoint(s) of evaluation of this end point
    At the end of cycles 3,6,9,12, and 15; at EOT; then every
    12 weeks for a minimum of 24 months, and then every 6 months until disease progression or study closure
    Al final de los ciclos 3, 6, 9, 12 y 15; al final del tratamiento. Posteriormente cada 12 semanas durante un mínimo de 24 meses y posteriormente cada 6 meses hasta progresión de la enfermedad o cierre del ensayo.
    E.5.2Secondary end point(s)
    To determine the proportion of patients achieving complete response (CR)
    Determinar la proporción de pacientes que logren Respuesta Completa (RC).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Does not have a specific timepoint.
    No hay visita específica.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.6.13.1Other scope of the trial description
    Immunogenicity and biomarker analysis
    Inmunogenicidad y análisis de biomarcadores
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA27
    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
    Austria
    Belgium
    Brazil
    France
    Germany
    Italy
    Netherlands
    Poland
    Spain
    Switzerland
    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
    Last visit of the last subject.
    última visita del último paciente
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    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: 105
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 19
    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 state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 72
    F.4.2.2In the whole clinical trial 124
    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)
    For patients who complete 16 cycles of brentuximab vedotin, re-initiation of brentuximab vedotin may be permitted at the joint discretion of the sponsor and investigator. For patients who complete 48 weeks of reference theraphy, initiation of subsequent standard-of-care theraphy should be discussed with the study doctor.
    En los pacientes que hayan sido tratados con 16 ciclos de brentuximab vedotin, se permitirá el reinicio del tratamiento con brentuximab vedotin bajo el criterio conjunto del promotor y del investigador. Para los pacientes que hayan completado 48 semanas de tratamiento de referencia, se discutirá el inicio de la terapia estándar posterior con el investigador del estudio.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-06-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-06-08
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-07-06
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