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    Summary
    EudraCT Number:2020-000382-16
    Sponsor's Protocol Code Number:1063-Dara-H-VERUMM
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-11-04
    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 ConcernedGermany - PEI
    A.2EudraCT number2020-000382-16
    A.3Full title of the trial
    Efficacy of daratumumab (Dara) retreatment using a histone deacetylase-inhibitor (HDACi: panobinostat) as a Dara-longevity-inducing, epigenetic agent in combination with bortezomib-dexamethasone as a quadruplet in relapsed / refractory multiple myeloma (RRMM) patients
    Wirksamkeit einer wiederholten Daratumumab (Dara)-therapie unter Verwendung eines Histon-Deacetylase-Inhibitors (HDACi: Panobinostat) als epigenetischer Wirkstoff mit Potential zur Induktion einer Dara-Langzeitwirkung in Kombination mit Bortezomib-Dexamethason als Quadruplett bei Patienten mit rezidiviertem/refraktärem Multiplem Myelom (RRMM)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy of daratumumab (Dara) retreatment of relapsed/ refractory multiple myeloma (RRMM) patients in combination with panobinostat, bortezomib-and dexamethasone
    Wirksamkeit einer wiederholten Daratumumab (Dara) Behandlung von Patienten mit rezidiviertem/refraktärem Multiplen Myelom (RRMM) in Kombination mit Panobinostat, Bortezomib und Dexamethason
    A.3.2Name or abbreviated title of the trial where available
    Dara-H-VERUMM
    Dara-H-VERUMM
    A.4.1Sponsor's protocol code number1063-Dara-H-VERUMM
    A.5.4Other Identifiers
    Name:DRKSNumber:DRKS00020561
    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 SponsorMedical Center - University of Freiburg
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportUniversity of Freiburg, Faculty of Medicine
    B.4.2CountryGermany
    B.4.1Name of organisation providing supportJanssen-Cilag GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedical Center - University of Freiburg
    B.5.2Functional name of contact pointDepartment for Medicine I, ECTU
    B.5.3 Address:
    B.5.3.1Street AddressHugstetter Straße 55
    B.5.3.2Town/ cityFreiburg
    B.5.3.3Post code79106
    B.5.3.4CountryGermany
    B.5.4Telephone number+4976127032902
    B.5.5Fax number+4976127033180
    B.5.6E-mailmatthias.weiss@uniklinik-freiburg.de
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Daratumumab (DARZALEX® 1.800 mg Injektionslösung)
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV Turnhoutseweg 30 2340 Beerse Belgien
    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 nameDarzalex
    D.3.2Product code L01XC24
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    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: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Farydak (Panobinostat)
    D.2.1.1.2Name of the Marketing Authorisation holderSecura Bio Limited 32 Molesworth Street Dublin D02 Y512 Republic of Ireland
    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 nameFarydak
    D.3.2Product code L01XX42
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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 Yes
    D.2.1.1.1Trade name Velcade (Bortezomib)
    D.2.1.1.2Name of the Marketing Authorisation holderJANSSEN-CILAG INTERNATIONAL NV Turnhoutseweg 30 B-2340 Beerse Belgien
    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 nameVelcade
    D.3.2Product code L01XX32
    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.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Relapsed and refractory multiple myeloma
    Rezidives und refraktäres Multiples Myelom
    E.1.1.1Medical condition in easily understood language
    Relapsed and refractory multiple myeloma
    wiederkehrendes / therapieresistentes Multiples Myelom
    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 No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this trial is a first evaluation of Dara-retreatment, applying a sensibly-dosed and well-tolerable 4-agent combination schedule of Dara s.c., with regard to efficacy and treatment longevity.
    Dara-panobinostat (Pan) bortezomib (V) dexamethasone (D) should therefore be equally potent to Dara-VD in pts with 2 prior lines in the CASTOR-trial
    Das Hauptziel dieser Studie ist eine erste Bewertung der wiederholten Dara-Behandlung unter Anwendung einer angemessen dosierten und gut verträglichen 4er-Kombinationstherapie von Dara s.c. hinsichtlich Wirksamkeit und Dauer des Ansprechens auf die Behandlung.
    Dara-Panobinostast (Pan) -Bortezomib (V) Dexamethason (D) sollte daher bei Patienten mit 2 vorangegangenen Therapielinien die gleiche Wirksamkeit aufweisen wie Dara-VD in der CASTOR-Studie.
    E.2.2Secondary objectives of the trial
    Secondary study objectives will be analysed descriptively:
    • Characterize the response to Dara-PanVD, response duration, PFS, OS
    and QoL and fitness (according to R-MCI) in RR MM pts
    • Assess the phenotype, CD38-expression, MRD, mass cytometry and
    sequencing analyses (biomarker correlation analysis) in RRMM treated
    with Dara-PanVD.
    • Comparison of tolerance, efficacy and CD38 preservation of Dara-PanV
    vs. Dara-V maintenance from cycle 9 onwards until PD.
    Sekundäre Studienziele werden deskriptiv analysiert:
    • Charakterisierung der Reaktion auf Dara-PanVD, Reaktionsdauer, PFS, OS und QoL und Fitness (nach R-MCI) in RR MM pts
    • Beurteilung des Phänotyps, CD38-Expression, MRD, Massenzytometrie und Sequenzierungsanalysen (Biomarker-Korrelationsanalyse) bei mit Dara-PanVD behandeltem RRMM.
    • Vergleich von Toleranz, Wirksamkeit und CD38- Präservierung von Dara-PanV vs. Dara-V-Erhaltungstherapie ab Zyklus 9 bis zur PD.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female patients ≥18 years of age
    2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
    3. Patients with a confirmed diagnosis of multiple myeloma (in line with the revised IMWG criteria) who have received Dara-Rd as relapse treatment in 2nd line and have documented evidence of PD based on the investigator’s determination of response as defined by the IMWG uniform response criteria.
    (Patients who have received a prior autologous bone marrow transplant and otherwise meet the inclusion criteria are eligible for this study)
    4. Must have measurable disease defined by at least 1 of the following 3
    measurements:
    ● Serum M-protein ≥0.5 g/dL
    ● Urine M-protein ≥200 mg/24 hours OR
    ● Serum Free Light Chain (FLC) >100 mg/L of involved FLC
    5. Laboratory test results within these ranges:
    • White blood cell count ≥2 x 109/L
    • Absolute neutrophil (ANC) count ≥0.5 x 109/L
    • Platelet count ≥75 x 109/L
    • Haemoglobin >8 g/dL
    • Calculated creatinine clearance (according to MDRD) ≥30 mL/minute
    • Total bilirubin ≤1.5 x upper limit of normal (ULN)
    • AST and ALT ≤2.5 x ULN
    • Corrected serum calcium level <3.5 mmol/L (<14 mg/dL)
    6. Women of childbearing potential (WOCBP) must have 2 negative serum pregnancy tests, one 10-14 days prior to start of the study drugs and one within 24 hours prior to the start of study drugs. Women must not be breastfeeding. WOCBP must agree to follow instructions for methods of contraception for 4 weeks before the start of treatment with study drugs, for the duration of treatment with study drugs, and for a total of 3 months after cessation of daratumumab treatment. Males who are sexually active with WOCBP must always use a latex or synthetic condom during any sexual contact with females of reproductive potential, even if they have undergone a successful vasectomy.
    7. Written informed consent obtained according to international guidelines and local laws;
    8. Ability to understand the nature of the trial and comply with the trial related procedures.
    1. Männliche oder weibliche Patienten ≥18 Jahre alt.
    2. Leistungsstatus der Eastern Cooperative Oncology Group (ECOG) 0 bis 2.
    3. Patienten mit einer bestätigten Diagnose des Multiplen Myeloms (gemäß den überarbeiteten IMWG-Kriterien), die Dara-Rd als Rückfallbehandlung in der 2. Linie erhalten haben und die ein dokumentiertes Fortschreiten der Erkrankung (PD) aufweisen, welches durch den Prüfarzt anhand der einheitlichen IMWG Kriterien zum Therapie-Ansprechen festgestellt wurde.
    (Patienten, die zuvor eine autologe Knochenmarkstransplantation erhalten haben und ansonsten die Einschlusskriterien erfüllen, kommen für diese Studie in Frage)
    4. Vorhandensein einer messbaren Erkrankung, die durch mindestens 1 der folgenden 3 Parameter definiert ist:
    ● Serum M-Protein ≥0.5 g/dL
    ● Urin M-Protein ≥200 mg/24 Stunden ODER
    ● freie leichte Ketten (FLC) im Serum >100 mg/L beteiligter FLC
    5. Labortestergebnisse innerhalb dieser Bereiche:
    ● Anzahl der weißen Blutkörperchen ≥2 x 109/L
    ● Absolute Neutrophilen (ANC) ≥0.5 x 109/L
    ● Thrombozytenzahl ≥75 x 109/L
    ● Hämoglobin >8 g/dL
    ● Berechnete Kreatinin-Clearance (nach MDRD) ≥30 mL/min
    ● Gesamtbilirubin ≤1.5 x obere Normgrenze (ULN)
    ● AST und ALT ≤2.5 x ULN
    ● Korrigierter Serum-Kalziumspiegel <3,5 mmol/L (<14 mg/dL).
    6. Frauen im gebärfähigen Alter (WOCBP) müssen zwei negative Serum-Schwangerschaftstests vorweisen, einen 10-14 Tage vor Beginn der Studienmedikation und einen innerhalb von 24 Stunden vor Beginn der Studienmedikation. Frauen dürfen nicht stillen. WOCBP müssen sich damit einverstanden erklären, 4 Wochen vor Beginn der Behandlung mit den Studienmedikamenten, während der Dauer der Behandlung mit den Studienmedikamenten und für insgesamt 3 Monaten nach Beendigung der Daratumumab-Behandlung die Anweisungen zu sicheren Verhütungsmethoden zu befolgen. Männer, die mit WOCBP sexuell aktiv sind, müssen bei jedem sexuellen Kontakt mit WOCBP stets ein Latex- oder synthetisches Kondom verwenden, auch wenn sie sich einer erfolgreichen Vasektomie unterzogen haben.
    7. Schriftliche Einverständniserklärung, die nach internationalen Richtlinien und örtlichen Gesetzen eingeholt wird.
    8. Fähigkeit, die Art der Studie und die mit der Studie verbundenen Verfahren zu verstehen und diese einzuhalten.
    E.4Principal exclusion criteria
    1. Plasma cell leukaemia, and/or extensive EM relapse (=multiple, large sites); entirely refractory MM disease, documented systemic light chain amyloidosis, MM involving the central nervous system
    2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
    3. Waldenström’s macroglobulinemia or IgM myeloma
    4. Clinical signs of meningeal involvement of multiple myeloma
    5. Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted. (FEV1 testing is, required during screening)
    6. Known intolerance to or contraindication for the use of bortezomib, or refractory to bortezomib (defined as progressive disease according to IMWG criteria
    7. Known intolerance to or contraindication for the use of daratumumab, panobinostat, and dexamethasone or any of the other ingredients in the study treatment formulations (known hypersensitivity to the active substances or any of the excipients)
    8. Life expectancy of <4 months
    9. Major surgery within 4 weeks prior to cycle 1 day 1
    10. Subject is known to be seropositive for human immunodeficiency virus (HIV) or has active hepatitis (type A, B or hepatitis C)
    11. Any serious underlying medical condition, such as:
    • serious active viral, bacterial, or uncontrolled systemic fungal infection
    • severe cognitive disorders
    • severe ventricular arrhythmia
    12. Participation in any other interventional clinical trial within the last 30 days before the start of this trial
    13. Any prior or concurrent malignancy other than multiple myeloma.
    Exceptions include patients who have been disease-free for at least five
    years before study entry or patients with adequately treated and
    completely resected basal cell or squamous cell skin cancer, in situ
    cervical, breast or prostate cancer
    14. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
    15. Known or persistent abuse of medication, drugs or alcohol; Subject is known or suspected of not being able to comply with study protocol
    16. Current or planned pregnancy, nursing period
    17. Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception
    Women of childbearing potential can only take part in this study if the risk of becoming pregnant is absolutely minimized. Save contraceptive methods comprise: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception and have to be used while participating in the study.
    Men must agree to use a latex condom during sexual contact with females of childbearing potential while participating in this study even if he has undergone a successful vasectomy. Patients must abstain from donating blood, semen, or sperm during participation in the study

    1. Plasmazellleukämie und / oder ausgedehnter EM-Rückfall (= mehrere große Stellen); vollständig refraktäre MM-Krankheit, dokumentierte systemische Leichtketten-Amyloidose, MM mit Beteiligung des Zentralnervensystems.
    2. POEMS-Syndrom (Polyneuropathie, Organomegalie, Endokrinopathie, monoklonales Protein und Hautveränderungen)
    3. Morbus Waldenström oder IgM-Myelom
    4. Klinische Anzeichen einer meningealen Beteiligung des Multiplen Myeloms
    5. Chronisch obstruktive Lungenerkrankung (COPD) mit einer expiratorischen Einsekundenkapazität (FEV1) von <50% des Vorhergesagten Wertes (FEV1-Test ist während des Screenings erforderlich)
    6. Bekannte Unverträglichkeit auf oder Kontraindikation für die Anwendung von Bortezomib oder refraktär auf eine Behandlung mit Bortezomib (definiert als fortschreitende Erkrankung nach IMWG-Kriterien)
    7. Bekannte Unverträglichkeit auf oder Kontraindikation für die Anwendung von Daratumumab, Panobinostat und Dexamethason oder eines der anderen Inhaltsstoffe in den Studienbehandlungsformulierungen (bekannte Überempfindlichkeit gegen die Wirkstoffe oder einen der Hilfsstoffe)
    8. Lebenserwartung von <4 Monaten
    9. Größerer operativer Eingriff innerhalb von 4 Wochen vor Zyklus 1 Tag 1
    10. Patient ist seropositiv für das humane Immundefizienzvirus (HIV) oder hat eine aktive Hepatitis (Typ A, B oder Hepatitis C).
    11. Jede ernste medizinische Grunderkrankung, wie z.B:
    • ernste aktive virale, bakterielle Infektion oder unkontrollierte systemische Pilzinfektion
    • schwere kognitive Störungen
    • schwere ventrikuläre Arrhythmie
    12. Teilnahme an einer anderen interventionellen klinischen Studie innerhalb der letzten 30 Tage vor Beginn dieser Studie.
    13. Jegliche frühere oder gleichzeitige Malignität außer dem multiplen Myelom
    Ausgenommen sind Patienten, die seit mindestens fünf Jahren vor Studieneinschluss krankheitsfrei waren oder Patienten mit adäquat behandeltem und vollständig reseziertem Basalzell- oder Plattenepithelkarzinom der Haut, in situ Gebärmutterhals-, Brust- oder Prostatakrebs.
    14. Patienten ohne Rechtsfähigkeit, die die Art, die Bedeutung und die Folgen der Studienbehandlung nicht verstehen können.
    15. Bekannter oder anhaltender Missbrauch von Medikamenten, Drogen oder Alkohol; Patienten bei denen bekannt ist oder vermutet wird, dass der Proband das Studienprotokoll nicht einhalten kann.
    16. Aktuelle oder geplante Schwangerschaft, Stillzeit.
    17. Nichtanwendung einer der folgenden sicheren Verhütungsmethoden: Kondome für Frauen, Diaphragma oder Spirale, jeweils in Kombination mit Spermiziden; Intrauterinpessar; hormonelle Empfängnisverhütung in Kombination mit einer mechanischen Verhütungsmethode.
    Frauen im gebärfähigen Alter (WOCBP) können nur dann an dieser Studie teilnehmen, wenn das Risiko, schwanger zu werden, absolut minimiert ist. Sichere Verhütungsmethoden sind: Frauenkondome, Diaphragma oder Spirale, jeweils in Kombination mit Spermiziden; Intrauterinpessar; hormonale Verhütung in Kombination mit einer mechanischen Verhütungsmethode müssen während der Teilnahme an der Studie verwendet werden.
    Männer müssen sich damit einverstanden erklären, während der Teilnahme an dieser Studie bei sexuellen Kontakten mit Frauen im gebärfähigen Alter ein Latexkondom zu verwenden, selbst wenn er sich einer erfolgreichen Vasektomie unterzogen hat. Die Patienten müssen darauf verzichten, während der Teilnahme an der Studie Blut, Samen oder Sperma zu spenden.
    E.5 End points
    E.5.1Primary end point(s)
    Response to Dara-PanVD,
    Ansprechen auf Dara-Pan-VD,
    E.5.1.1Timepoint(s) of evaluation of this end point
    within 2 weeks after end of cycle 8
    innerhalb von 2 Wochen nach Ende von Zyklus 8
    E.5.2Secondary end point(s)
    Overall survival (OS), Progression-free survival (PFS), response duration, Minimal residual disease (MRD), Quality of Life (QoL), fitness assessment via R-MCI, safety (grade 3/4 toxicities under Dara-PanVD according to National cancer institute – common terminology criteria for adverse events (NCI-CTCAE) version 5.0, adverse events, serious adverse events. Early death within initial 6 + 12 months, biomarker studies before, during and at end of the study medication. Treatment longevity assessed as number of Dara-PanVD / Dara-(Pan)V cycles given.
    Gesamtüberleben (OS), progressionsfreies Überleben (PFS), Ansprechdauer, minimale Resterkrankung (MRD), Lebensqualität (QoL), Fitnessbewertung nach R-MCI, Sicherheit (Grad 3/4 Toxizität unter Dara-PanVD laut Nationalem Krebsinstitut - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, unerwünschte Ereignisse, schwerwiegende unerwünschte Ereignisse. Frühzeitiger Tod innerhalb der ersten 6 + 12 Monate, Biomarkerstudien vor, während und am Ende der Studienmedikation. Die Langlebigkeit der Behandlung wird als Anzahl von verabreichten Dara-PanVD / Dara- (Pan) V-Zyklen angegeben.
    E.5.2.1Timepoint(s) of evaluation of this end point
    OS and PFS calculated as time from start of treatment until death or first observation of PD. Patients without an event of interest will be considered as censored observations at the time last seen alive/without observation of disease progression. OS and PFS will be estimated using the Kaplan Meier method. The comparison of QoL pre- and posttreatment will be evaluated with the Wilcoxon’s signed rank test in patients where both assessments are available. The analysis of the randomized part of this trial will be considered as exploratory. OS, PFS (calculated from randomization) will be compared between randomized groups based on the Intention-to-treat-principle, i.e. all randomized patients will be analysed irrespective of protocol deviations in the treatment group they were allocated to.
    OS und PFS werden als Zeit von Beginn der Behandlung bis Tod oder der ersten Beobachtung des Fortschreitens der Erkrankung berechnet. Patienten ohne ein Ereignis von Interesse werden als zensierte Beobachtungen zum Zeitpunkt zuletzt lebend gesehen bzw. ohne Beobachtung des Krankheitsfortschritts betrachtet. OS und PFS werden mit der Kaplan-Meier-Methode geschätzt. Der Vergleich der Lebensqualität vor und nach der Behandlung wird bei Patienten, bei denen beide Bewertungen vorliegen, mit dem Wilcoxon-Vorzeichen-Rang-Test ausgewertet. Die Analyse des randomisierten Teils dieser Studie wird als explorativ betrachtet. OS, PFS werden zwischen randomisierten Gruppen auf der Grundlage des Intention-to-treat-Prinzips verglichen.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled 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 Yes
    E.8.1.7.1Other trial design description
    randomisierte Erhaltungstherapie (2 armig)
    randomized maintenance (2 arms)
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    randomisierte Erhaltungstherapie (2 armig)- DaraPanV vs DaraV
    randomized maintenance (2 arms) - DaraPanV vs DaraV
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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 trial defined as last patient last visit (LPLV)
    Ende der Studie definiert als letzter Patientenvisit des als letztes eingeschlossenen Patienten (LPLV)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months60
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months60
    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: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 No
    F.3.3.1Women of childbearing potential not using contraception Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women Information not present in EudraCT
    F.3.3.4Nursing women Information not present in EudraCT
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    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)
    Dara-PanV vs. Dara-V as maintenance treatment schedules are being performed until progression, intolerance or upon patients'/physicians' discretion or 24 months after registration of the last patient (whichever occurs first)
    Dara-PanV vs. Dara-V als Erhaltungsbehandlung werden bis PD oder inakzeptable Toxizität oder 24 Monate nach der Registrierung des letzten Patienten verabreicht (je nachdem, was zuerst eintritt)
    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 Decision2021-03-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-04-07
    P. End of Trial
    P.End of Trial StatusOngoing
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