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   40109   clinical trials with a EudraCT protocol, of which   6567   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

    Download PDF

    Clinical Trial Results:
    Phase II Trial of Plitidepsin (Aplidin®) in Combination with Bortezomib and Dexamethasone in Multiple Myeloma Patients Double Refractory to Bortezomib and Lenalidomide .

    Summary
    EudraCT number
    2015-003486-29
    Trial protocol
    ES   FR  
    Global end of trial date
    30 Jul 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    29 May 2019
    First version publication date
    29 May 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    APL-B-022-15
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03117361
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pharma Mar, S.A.
    Sponsor organisation address
    Avenida de los Reyes, 1 Polígono Industrial "La Mina", Colmenar Viejo, Madrid, Spain, 28770
    Public contact
    Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit., Pharmamar, S.A., 34 918466000, clinicaltrials@pharmamar.com
    Scientific contact
    Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit., Pharmamar, S.A., 34 918466000, clinicaltrials@pharmamar.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Mar 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Jul 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jul 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of plitidepsin in combination with bortezomib and dexamethasone in patients with multiple myeloma (MM) double refractory to bortezomib and lenalidomide in terms of overall response rate (ORR), including stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR).
    Protection of trial subjects
    The study was in compliance with ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    All patients had to receive the following i.v. prophylactic medication 30-60 minutes before each infusion of plitidepsin: - Ondansetron 8 mg i.v. or equivalent, - Diphenhydramine hydrochloride 25 mg i.v. or equivalent, - Ranitidine 50 mg i.v. or equivalent. If necessary, in addition to the above, 10 mg of metoclopramide every eight hours could be administered after the end of plitidepsin infusion or the duration of treatment with serotonin (5-HT3) antagonists and/or DXM could be extended. Prophylactic antiemetic medication for BTZ was given according to the Investigator’s criteria. Herpes virus infection prophylaxis had to be given while the patients were on BTZ therapy.
    Evidence for comparator
    -
    Actual start date of recruitment
    08 May 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Italy: 4
    Worldwide total number of subjects
    10
    EEA total number of subjects
    10
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    8
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Patients participated between 15May2017-30Jul2018 (last follow-up cutoff date). The 1st dose/1st cycle was administered on 15May2017 and the last dose/last cycle on 23Jul2018. At cutoff date 10 patients had been included and treated with plitidepsin+BTZ+DXM and they were evaluable for safety. 8 of these were evaluable for the efficacy endpoint

    Pre-assignment
    Screening details
    IC signed;Age≥18 years;confirmed diagnosis of MM,ECOG PS≤2;LVEF≥45%;negative pregnancy test

    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded
    Blinding implementation details
    Not applicable

    Arms
    Arm title
    Plitidepsin+BTZ+DXM
    Arm description
    Plitidepsin was to be administered as a 3-hour (h) intravenous (i.v.) infusion at a dose of 5 mg/m2, on Day (D) 1 and 15, every four weeks (q4wk); BTZ was to be administered as a subcutaneous (s.c.) injection at a dose of 1.3 mg/m2 on D1, 4, 8 and 11, q4wk and DXM was to be taken orally at a dose of 40 mg/day on D1, 8, 15 and 22, q4wk. A cycle was defined as 28 days, plus any additional days required for dosing delays due to any reason. Treatment cycles were repeated q4wk.
    Arm type
    Experimental

    Investigational medicinal product name
    Plitidepsin
    Investigational medicinal product code
    Plitidepsin
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3-hour i.v. infusion at a dose of 5 mg/m2 on Days 1 and 15 every four weeks (q4wk)

    Investigational medicinal product name
    Bortezomib
    Investigational medicinal product code
    BTZ
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3-5-second bolus s.c. injection at a dose of 1.3 mg/m2 on Days 1, 4, 8 and 11 q4wk, one minute after the end of the plitidepsin infusion

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    DXM
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    at least one hour before the administration of plitidepsin infusion at a dose of 40 mg/day on Days 1, 8, 15 and 22 q4wk.

    Number of subjects in period 1
    Plitidepsin+BTZ+DXM
    Started
    10
    Completed
    0
    Not completed
    10
         Progressive disease
    5
         Death
    1
         Physician decision
    2
         On study treatment at the end of study
    1
         Treatment-related adverse event
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall period
    Reporting group description
    -

    Reporting group values
    Overall period Total
    Number of subjects
    10 10
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    8 8
        From 65-84 years
    2 2
    Age continuous
    Units: years
        median (full range (min-max))
    59 (43 to 72) -
    Gender categorical
    Units: Subjects
        Female
    5 5
        Male
    5 5
    Race
    Units: Subjects
        White
    7 7
        Other
    3 3
    ECOG PS
    ECOG PS, Eastern Cooperative Oncology Group performance status
    Units: Subjects
        PS 0
    5 5
        PS 1
    4 4
        PS 2
    1 1
    MM type at diagnosis
    MM, multiple myeloma
    Units: Subjects
        Secretory IgA
    2 2
        Secretory IgG
    4 4
        Secretory Kappa light-chain disease
    2 2
        Secretory Lambda light-chain disease
    2 2
    Durie-Salmon stage and subclassification at diagnosis
    Four patients had missing data in stage and sub-classification: 2 patients had no Durie-Salmon stage and sub-classification data at diagnosis; and 2 patients were stage III, but had no Durie-Salmon sub-classification at diagnosis.
    Units: Subjects
        IIA
    2 2
        IIIA
    3 3
        IIIB
    1 1
        Missing
    4 4
    ISS stage at diagnosis
    ISS, International Staging System
    Units: Subjects
        ISS I
    1 1
        ISS II
    1 1
        ISS III
    4 4
        Not done
    4 4
    R-ISS stage at study entry
    ISS, International Staging System
    Units: Subjects
        II (Not R-ISS I stage or III)
    3 3
        III (ISS stage III and either high-risk CA)
    3 3
        Non available genetic results
    4 4
    Cytogenetic at study entry
    Units: Subjects
        High risk
    2 2
        Standard risk
    4 4
        Non available genetic results
    4 4
    Disease status with respect to last prior therapy
    Total refractory MM included 2 categories of refractory: - Primary Refractory: disease that was non-responsive in patients who had never achieved a MR or better, with any therapy. It included patients who never achieved MR or better, in whom there was no significant change in M-protein and no evidence of clinical progression, as well as primary, refractory PD where patients met criteria for true PD. - Relapsed and refractory: disease that was non-responsive while on salvage therapy, or progressed within 60 days of the last therapy in patients who had achieved MR or better at some point
    Units: Subjects
        Primary Refractory
    7 7
        Relapsed and refractory
    3 3
    Best response to last prior anticancer therapy
    MR, minimal response; PD, disease progression; PR, partial response; SD, stable disease
    Units: Subjects
        PR
    2 2
        MR
    1 1
        SD
    2 2
        PD
    5 5
    Prior HSCT
    HSCT, hematopoietic stem cell transplantation
    Units: Subjects
        Autologous
    6 6
        Autologous and allogenic
    2 2
        No
    2 2
    Lines of prior chemotherapy
    Units: Subjects
        3 lines
    1 1
        4 lines
    2 2
        5 lines
    4 4
        8 lines
    2 2
        9 lines
    1 1
    Weight
    Units: kg
        median (full range (min-max))
    71.4 (51.0 to 105.3) -
    Height
    Units: cm
        median (full range (min-max))
    167.1 (152 to 186) -
    BSA
    BSA, body surface area;
    Units: m2
        median (full range (min-max))
    1.8 (1.5 to 2.2) -
    Time from diagnosis to first plitidepsin infusion
    Units: months
        median (full range (min-max))
    70.7 (16 to 168) -
    Time from last progressive disease to first infusion
    Units: weeks
        median (full range (min-max))
    5.3 (2 to 14) -
    Lines of prior chemotherapy
    Units: number of lines
        median (full range (min-max))
    5 (3 to 9) -
    Agents of prior chemotherapy
    Units: number of agents
        median (full range (min-max))
    9 (5 to 13) -
    TTP to last anticancer therapy
    TTP, time to progression
    Units: months
        median (full range (min-max))
    3.4 (1.6 to 10.6) -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Plitidepsin+BTZ+DXM
    Reporting group description
    Plitidepsin was to be administered as a 3-hour (h) intravenous (i.v.) infusion at a dose of 5 mg/m2, on Day (D) 1 and 15, every four weeks (q4wk); BTZ was to be administered as a subcutaneous (s.c.) injection at a dose of 1.3 mg/m2 on D1, 4, 8 and 11, q4wk and DXM was to be taken orally at a dose of 40 mg/day on D1, 8, 15 and 22, q4wk. A cycle was defined as 28 days, plus any additional days required for dosing delays due to any reason. Treatment cycles were repeated q4wk.

    Primary: Overall Response Rate

    Close Top of page
    End point title
    Overall Response Rate [1]
    End point description
    The primary analysis should have been done once a total of 64 patients have received plitidepsin+BTZ+DXM, with one futility analysis planned after the inclusion of 20 evaluable patients that had completed two full treatment cycles. However, only a total of 10 patients were included and treated, of whom eight were evaluable for the primary efficacy endpoint (ORR including PR or better according to IMWG criteria). As a result of slow patient accrual, the study was closed before reaching the target enrollment of 20 patients for the first futility analysis. Therefore, the required sample size was not reached and only descriptive data in the population of patients evaluable for efficacy (no formal assessment) are provided. MR,minimal response;ORR,overall response rate;PD,disease progression;PR,partial response;SD,stable disease ORR (95%CI) = 12.5% (0.3-52.7%) Clinical benefit rate (MR or better)[95%CI] = 25.0% [3.2-65.1%] Disease control rate (SD or better)[95%CI] = 87.5% [47.3-99.7%]
    End point type
    Primary
    End point timeframe
    Overall period
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The required sample size was not reached and only descriptive data in the population of patients evaluable for efficacy (no formal assessment) of the primary endpoint are provided
    End point values
    Plitidepsin+BTZ+DXM
    Number of subjects analysed
    8 [2]
    Units: subjects
        PR
    1
        MR
    1
        SD
    5
        PD
    1
    Notes
    [2] - 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs
    No statistical analyses for this end point

    Secondary: Duration of Response

    Close Top of page
    End point title
    Duration of Response
    End point description
    End point type
    Secondary
    End point timeframe
    Overall period
    End point values
    Plitidepsin+BTZ+DXM
    Number of subjects analysed
    1 [3]
    Units: months
        number (not applicable)
    9.2
    Notes
    [3] - Only one patient achieved a partial response
    No statistical analyses for this end point

    Secondary: Time to Progression

    Close Top of page
    End point title
    Time to Progression
    End point description
    TTP, time to progression; 999, not reached. Events: 6 (75.0%) TTP at 3 months (95% CI) 37.5% (4.0-71.0%) TTP at 6 months (95% CI) 25.0% (0-55.0%) TTP at 12 months (95% CI) 25.0% (0-55.0%)
    End point type
    Secondary
    End point timeframe
    Overall period
    End point values
    Plitidepsin+BTZ+DXM
    Number of subjects analysed
    8 [4]
    Units: months
        median (confidence interval 95%)
    2.7 (0.7 to 999)
    Notes
    [4] - 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs
    No statistical analyses for this end point

    Secondary: Progression-free Survival

    Close Top of page
    End point title
    Progression-free Survival
    End point description
    PFS, progression-free survival; 999, not reached Events 6 (75.0%) PFS at 3 months (95% CI) 37.5% (4.0-71.0%) PFS at 6 months (95% CI) 25.0% (0-55.0%) PFS at 12 months (95% CI) 25.0% (0-55.0%)
    End point type
    Secondary
    End point timeframe
    Overall period
    End point values
    Plitidepsin+BTZ+DXM
    Number of subjects analysed
    8 [5]
    Units: months
        median (confidence interval 95%)
    2.7 (0.7 to 999)
    Notes
    [5] - 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs
    No statistical analyses for this end point

    Secondary: Event-free Survival

    Close Top of page
    End point title
    Event-free Survival
    End point description
    EFS, Event-free survival; 999, not reached Events 6 (75.0%) EFS at 3 months (95% CI) 37.5% (4.0-71.0%) EFS at 6 months (95% CI) 25.0% (0-55.0%) EFS at 12 months (95% CI) 25.0% (0-55.0%)
    End point type
    Secondary
    End point timeframe
    Overall period
    End point values
    Plitidepsin+BTZ+DXM
    Number of subjects analysed
    8 [6]
    Units: months
        median (confidence interval 95%)
    2.7 (0.7 to 999)
    Notes
    [6] - 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs
    No statistical analyses for this end point

    Secondary: Overall Survival

    Close Top of page
    End point title
    Overall Survival
    End point description
    OS, overall survival; 999, not reached Events 2 (25.0%) OS at 6 months (95% CI) 55.6% (6.9-100.0%) OS at 12 months (95% CI) 55.6% (6.9-100.0%)
    End point type
    Secondary
    End point timeframe
    Overall period
    End point values
    Plitidepsin+BTZ+DXM
    Number of subjects analysed
    8 [7]
    Units: months
        median (confidence interval 95%)
    999 (2.3 to 999)
    Notes
    [7] - 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Overall period
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Plitidepsin+BTZ+DXM
    Reporting group description
    Plitidepsin was to be administered as a 3-hour (h) intravenous (i.v.) infusion at a dose of 5 mg/m2, on Day (D) 1 and 15, q4wk; BTZ was to be administered as a subcutaneous (s.c.) injection at a dose of 1.3 mg/m2 on D1, 4, 8 and 11, q4wk and DXM was to be taken orally at a dose of 40 mg/day on D1, 8, 15 and 22, q4wk. A cycle was defined as 28 days, plus any additional days required for dosing delays due to any reason. Treatment cycles were repeated every four weeks (q4wk).

    Serious adverse events
    Plitidepsin+BTZ+DXM
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 10 (50.00%)
         number of deaths (all causes)
    3
         number of deaths resulting from adverse events
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Sciatica
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Rhabdomyolysis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Plitidepsin+BTZ+DXM
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 10 (100.00%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Hypertension
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    3
    Surgical and medical procedures
    Intramedullary rod insertion
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    General disorders and administration site conditions
    Asthenia/Fatigue
         subjects affected / exposed
    4 / 10 (40.00%)
         occurrences all number
    22
    Extravasation
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Malaise
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    7
    Peripheral swelling
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Pyrexia
         subjects affected / exposed
    4 / 10 (40.00%)
         occurrences all number
    6
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 10 (40.00%)
         occurrences all number
    12
    Antithrombin III decreased
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    2
    Blood cholesterol
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Neutrophil count decreased
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Weight decreased
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    3
    Respiratory, thoracic and mediastinal disorders
    Catarrh
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Cough
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Epistaxis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Respiratory failure
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 10 (60.00%)
         occurrences all number
    25
    Neutropenia
         subjects affected / exposed
    3 / 10 (30.00%)
         occurrences all number
    5
    Thrombocytopenia
         subjects affected / exposed
    4 / 10 (40.00%)
         occurrences all number
    35
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Neuropathy peripheral
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    14
    Sciatica
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    4
    Seizure
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    3
    Diarrhoea
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    7
    Gastric disorder
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Gingival bleeding
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Mouth haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Nausea
         subjects affected / exposed
    5 / 10 (50.00%)
         occurrences all number
    8
    Vomiting
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    2
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    7
    Back pain
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Muscular weakness
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    19
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Myalgia
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    3
    Hypercalcaemia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Hyperuricaemia
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    3
    Hypocalcaemia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Hypokalaemia
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    4
    Hypomagnesaemia
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    2
    Infections and infestations
    Folliculitis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Herpes zoster
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Influenza
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    29 May 2018
    On 29 May 2018, the Sponsor informed to the study centers and Investigators regarding its decision to close the recruitment of the APL-B-022-15 study. The study was terminated before reaching the target enrollment due to the slow patient accrual. Furthermore, the negative opinion of the European Medicines Agency (EMA) recommending the refusal of the marketing authorization for plitidepsin for the treatment of MM reinforced this Sponsor decision.
    -

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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