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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44335   clinical trials with a EudraCT protocol, of which   7366   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:
    A PHASE III, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THE EFFICACY AND SAFETY OF STANDARD SCHEDULE VERSUS A NEW ALGORITHM OF DOSE REDUCTIONS IN ELDERLY AND UNFIT NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS RECEIVING LENALIDOMIDE PLUS STEROIDS

    Summary
    EudraCT number
    		 2013-004166-33
    Trial protocol
    		 IT  
    Global end of trial date
    30 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Dec 2024
    First version publication date
    25 Dec 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RV-MM-PI-0752
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02215980
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Fondazione EMN Italy Onlus
    Sponsor organisation address
    Via Saluzzo 1/A, Torino, Italy, 10126
    Public contact
    Clinical Trial Office, Fondazione EMN Italy Onlus, +39 0110243236, clinicaltrialoffice@emnitaly.org
    Scientific contact
    Clinical Trial Office, Fondazione EMN Italy Onlus, +39 0110243236, clinicaltrialoffice@emnitaly.org
    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
    04 Dec 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jun 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy and the safety of the standard Rd schedule (arm A) versus an experimental approach including the standard Rd regimen as induction, followed by lenalidomide alone as maintenance (arm B).
    Protection of trial subjects
    The protocol for this study has been designed in accordance with the general ethical principles outlined in the Declaration of Helsinki. The review of this protocol by the IRB/EC and the performance of all aspects of the study, including the methods used for obtaining informed consent, must also be in accordance with principles enunciated in the declaration, as well as ICH Guidelines, Title 21 of the Code of Federal Regulations (CFR), Part 50 Protection of Human Subjects and Part 56 Institutional Review Boards.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Oct 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Safety
    Long term follow-up duration
    		 2 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 199
    Worldwide total number of subjects
    199
    EEA total number of subjects
    199
    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)
    0
    From 65 to 84 years
    199
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Unfit newly diagnosed multiple myeloma patients aged more than 65 and less than 80 years. Unfit patients will obtain a total score of 1 evaluating age, Charlson index, ADL and IADL indices.

    Pre-assignment
    Screening details
    		 Screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the evaluation of inclusion criteria described above. Subjects who meet all the inclusion criteria will be enrolled.

    Period 1
    Period 1 title
    Treatment period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 A: Rd
    Arm description
    		 - Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21. - Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days until progression or intolerance.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lenalidomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg/daily as oral administration (PO) on days 1-21

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral drops
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg as oral administration (PO) once weekly

    Arm title
    		 B: Rd-R (reduced)
    Arm description
    		 - Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21 - Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days, for a total of 9 cycles. Maintenance until progression or intolerance: - Lenalidomide: 10 mg/daily on days 1-21 of each 28-day cycle
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lenalidomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg/daily as oral administration (PO) on days 1-21. Each cycle will be repeated every 28 days, for a total of 9 cycles. Maintenance until progression or intolerance: 10 mg/daily on days 1-21 of each 28-day cycle

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral drops
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days, for a total of 9 cycles.

    Number of subjects in period 1
    		A: Rd B: Rd-R (reduced)
    Started
    98
    101
    Completed
    2
    6
    Not completed
    96
    95
         Adverse event, serious fatal
    10
    12
         Physician decision
    4
    4
         Consent withdrawn by subject
    3
    2
         Adverse event, non-fatal
    25
    25
         Other
    9
    2
         Lost to follow-up
    3
    2
         Lack of efficacy
    42
    47
         Protocol deviation
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    A: Rd
    Reporting group description
    		 - Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21. - Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days until progression or intolerance.

    Reporting group title
    B: Rd-R (reduced)
    Reporting group description
    		 - Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21 - Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days, for a total of 9 cycles. Maintenance until progression or intolerance: - Lenalidomide: 10 mg/daily on days 1-21 of each 28-day cycle

    Reporting group values
    		 A: Rd B: Rd-R (reduced) Total
    Number of subjects
    		 98 101 199
    Age categorical
    Patients >65 years and ≤ 80 years unfit and unsuitable, according to the investigator’s opinion, to receive approved first line treatments for newly diagnosed MM
    Units: Subjects
        >=72
    		 85 83 168
        < 72
    		 13 18 31
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 76 (74 to 79) 75 (75 to 77) -
    Gender categorical
    Units: Subjects
        Female
    		 49 48 97
        Male
    		 49 53 102
    ISS Stage
    Units: Subjects
        ISS I
    		 37 32 69
        ISS II
    		 36 48 84
        ISS III
    		 25 21 46
    ECOG
    Units: Subjects
        ECOG 0
    		 36 35 71
        ECOG 1
    		 51 50 101
        ECOG 2
    		 10 11 21
        ECOG NA
    		 1 5 6
    Subject analysis sets

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intention to trat

    Subject analysis sets values
    		 ITT
    Number of subjects
    199
    Age categorical
    Patients >65 years and ≤ 80 years unfit and unsuitable, according to the investigator’s opinion, to receive approved first line treatments for newly diagnosed MM
    Units: Subjects
        >=72
    168
        < 72
    31
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    76 (73 to 78)
    Gender categorical
    Units: Subjects
        Female
    97
        Male
    102
    ISS Stage
    Units: Subjects
        ISS I
    69
        ISS II
    84
        ISS III
    46
    ECOG
    Units: Subjects
        ECOG 0
    71
        ECOG 1
    101
        ECOG 2
    21
        ECOG NA
    6

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    A: Rd
    Reporting group description
    		 - Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21. - Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days until progression or intolerance.

    Reporting group title
    B: Rd-R (reduced)
    Reporting group description
    		 - Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21 - Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days, for a total of 9 cycles. Maintenance until progression or intolerance: - Lenalidomide: 10 mg/daily on days 1-21 of each 28-day cycle

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intention to trat

    Primary: Event Free Survival (EFS)

    		 Close Top of page
    End point title
    		 Event Free Survival (EFS)
    End point description
    Event-free survival (EFS) defined as: • Progression • Death for any cause • Discontinuation of lenalidomide therapy • Occurrence of any haematological grade 4 or non-haematological grade 3-4 adverse events (AES), including Secondary Primary Malignancies (SPMs)
    End point type
    Primary
    End point timeframe
    End ot Trial
    End point values
    		 A: Rd B: Rd-R (reduced)
    Number of subjects analysed
    98
    101
    Units: month
        median (confidence interval 95%)
    7.1 (6.1 to 11.5)
    10.1 (6 to 17)
    Statistical analysis title
    		 Log rank test
    Comparison groups
    A: Rd v B: Rd-R (reduced)
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.17
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 1.09
    Variability estimate
    Standard deviation
    Dispersion value
    0.14

    Secondary: time to progression (TTP)

    		 Close Top of page
    End point title
    		 time to progression (TTP)
    End point description
    End point type
    Secondary
    End point timeframe
    End of trial
    End point values
    		 A: Rd B: Rd-R (reduced)
    Number of subjects analysed
    98
    101
    Units: mon
        median (confidence interval 95%)
    21.9 (18 to 31.9)
    25.4 (18.4 to 36.1)
    Statistical analysis title
    		 Log rank test
    Comparison groups
    A: Rd v B: Rd-R (reduced)
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.56
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.27
    Variability estimate
    Standard deviation
    Dispersion value
    0.17

    Secondary: Progression Free Survival

    		 Close Top of page
    End point title
    		 Progression Free Survival
    End point description
    End point type
    Secondary
    End point timeframe
    End of trial
    End point values
    		 A: Rd B: Rd-R (reduced)
    Number of subjects analysed
    98
    101
    Units: month
        median (confidence interval 95%)
    19.3 (14.1 to 25.1)
    18.7 (14.4 to 28.8)
    Statistical analysis title
    		 Log rank test
    Comparison groups
    A: Rd v B: Rd-R (reduced)
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.29
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.15
    Variability estimate
    Standard deviation
    Dispersion value
    0.16

    Secondary: Overall response rate (ORR)

    		 Close Top of page
    End point title
    		 Overall response rate (ORR)
    End point description
    End point type
    Secondary
    End point timeframe
    End of trial
    End point values
    		 A: Rd B: Rd-R (reduced) ITT
    Number of subjects analysed
    98
    101
    199
    Units: patients
        >= PR
    31
    22
    53
        < PR
    67
    79
    146
    Statistical analysis title
    		 Fisher test
    Statistical analysis description
    Fisher test
    Comparison groups
    B: Rd-R (reduced) v A: Rd
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.149
    Method
    		 Fisher exact
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 3.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.32

    Secondary: time to next therapy (TNT)

    		 Close Top of page
    End point title
    		 time to next therapy (TNT)
    End point description
    End point type
    Secondary
    End point timeframe
    End of trial
    End point values
    		 A: Rd B: Rd-R (reduced)
    Number of subjects analysed
    98
    101
    Units: month
        median (confidence interval 95%)
    20.8 (16.7 to 32.8)
    28.4 (18 to 47.8)
    Statistical analysis title
    		 Log rank test
    Comparison groups
    A: Rd v B: Rd-R (reduced)
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.27
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1.15
    Variability estimate
    Standard deviation
    Dispersion value
    0.16

    Secondary: overall survival (OS)

    		 Close Top of page
    End point title
    		 overall survival (OS)
    End point description
    End point type
    Secondary
    End point timeframe
    End of trial
    End point values
    		 A: Rd B: Rd-R (reduced)
    Number of subjects analysed
    98
    101
    Units: month
        median (confidence interval 95%)
    47 (43.2 to 63.4)
    69.1 (49.1 to 102.2)
    Statistical analysis title
    		 Log rank test
    Comparison groups
    A: Rd v B: Rd-R (reduced)
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 1.09
    Variability estimate
    Standard deviation
    Dispersion value
    0.19

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    End of Trial
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27
    Reporting groups
    Reporting group title
    Per protocol
    Reporting group description
    		 -

    Serious adverse events
    		 Per protocol
    Total subjects affected by serious adverse events
         subjects affected / exposed
    105 / 199 (52.76%)
         number of deaths (all causes)
    111
         number of deaths resulting from adverse events
    22
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-acute lymphoblastic leukemia
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Adenocarcinoma gastric
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Sarcoma of skin
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Basosquamous carcinoma
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Bowen's disease
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intraductal papillary mucinous neoplasm
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Neuroendocrine carcinoma of the skin
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nodular melanoma
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Pulmonary embolism
         subjects affected / exposed
    4 / 199 (2.01%)
         occurrences causally related to treatment / all
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    Femoral hernia repair
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hospitalisation
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Completed suicide
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Death
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pain
         subjects affected / exposed
    4 / 199 (2.01%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    pyrexia
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Asthenia
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory failure
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Investigations
    Lipase increased
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    4 / 199 (2.01%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Bladder injury
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Injury
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Multiple fractures
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Rib fracture
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cardiac failure
         subjects affected / exposed
    5 / 199 (2.51%)
         occurrences causally related to treatment / all
    2 / 5
         deaths causally related to treatment / all
    0 / 2
    Cardiogenic shock
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Right ventricular failure
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    4 / 199 (2.01%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cerebrovascular accident
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    4 / 199 (2.01%)
         occurrences causally related to treatment / all
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Glaucoma
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    3 / 199 (1.51%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Large intestinal obstruction
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Erythema multiforme
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Toxic epidermal necrolysis
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    5 / 199 (2.51%)
         occurrences causally related to treatment / all
    5 / 5
         deaths causally related to treatment / all
    0 / 1
    Chronic kidney disease
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    3 / 199 (1.51%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pathological fracture
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    17 / 199 (8.54%)
         occurrences causally related to treatment / all
    11 / 18
         deaths causally related to treatment / all
    1 / 3
    Septic shock
         subjects affected / exposed
    6 / 199 (3.02%)
         occurrences causally related to treatment / all
    4 / 6
         deaths causally related to treatment / all
    1 / 2
    Sepsis
         subjects affected / exposed
    3 / 199 (1.51%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 1
    Pneumonia fungal
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Bronchitis
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 199 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Decreased appetite
         subjects affected / exposed
    2 / 199 (1.01%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Hyperkalemia
         subjects affected / exposed
    1 / 199 (0.50%)
         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
    		 Per protocol
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    152 / 199 (76.38%)
    Nervous system disorders
    Tremor
         subjects affected / exposed
    23 / 199 (11.56%)
         occurrences all number
    23
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    139 / 199 (69.85%)
         occurrences all number
    139
    Anaemia
         subjects affected / exposed
    74 / 199 (37.19%)
         occurrences all number
    74
    Thrombocytopenia
         subjects affected / exposed
    41 / 199 (20.60%)
         occurrences all number
    41
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    83 / 199 (41.71%)
         occurrences all number
    83
    Pyrexia
         subjects affected / exposed
    70 / 199 (35.18%)
         occurrences all number
    70
    Pain
         subjects affected / exposed
    67 / 199 (33.67%)
         occurrences all number
    67
    Asthenia
         subjects affected / exposed
    42 / 199 (21.11%)
         occurrences all number
    42
    Oedema peripheral
         subjects affected / exposed
    33 / 199 (16.58%)
         occurrences all number
    33
    Influenza like illness
         subjects affected / exposed
    28 / 199 (14.07%)
         occurrences all number
    28
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    130 / 199 (65.33%)
         occurrences all number
    130
    Constipation
         subjects affected / exposed
    61 / 199 (30.65%)
         occurrences all number
    61
    Nausea
         subjects affected / exposed
    27 / 199 (13.57%)
         occurrences all number
    27
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    27 / 199 (13.57%)
         occurrences all number
    27
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    31 / 199 (15.58%)
         occurrences all number
    31
    Erythema multiforme
         subjects affected / exposed
    23 / 199 (11.56%)
         occurrences all number
    23
    Dermatitis acneiform
         subjects affected / exposed
    15 / 199 (7.54%)
         occurrences all number
    15
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    20 / 199 (10.05%)
         occurrences all number
    20
    Back pain
         subjects affected / exposed
    11 / 199 (5.53%)
         occurrences all number
    11
    Bone pain
         subjects affected / exposed
    11 / 199 (5.53%)
         occurrences all number
    11
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    26 / 199 (13.07%)
         occurrences all number
    26
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    30 / 199 (15.08%)
         occurrences all number
    30

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jun 2015
    Amendment 1: Clarify inclusion/exclusion criteria, change of Sponsor legal representative , IB update.
    08 Nov 2016
    Amendment 2: Update Sponsor contacts, update criteria for assessing disease response, update side effects.
    01 Feb 2019
    Amendment 3: New drug distribution depot added (only AC and CEC).
    18 Jun 2019
    Amendment 4: IB update and side effects update.
    20 Mar 2020
    Urgent Amendment 1: Health emergency COVID-19.
    21 Oct 2020
    Amendment 5: IB update and side effects, Sponsor name change, insurance certificate update and other documents.
    31 Aug 2023
    Amendment CEC-CET: Change from CEC to CET.
    13 Nov 2023
    Amendment 6: Change of address of the centralised laboratory, Sponsor contacts and drug data updates.
    18 Jan 2024
    Amendment 7: Communication of closure of the study.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/33739404
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 10 01:15:21 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA