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    Clinical Trial Results:
    A Phase-Ib/II Study of Ruxolitinib and Pomalidomide Combination Therapy in Patients with Primary and Secondary Myelofibrosis

    Summary
    EudraCT number
    		 2012-002431-29
    Trial protocol
    		 DE  
    Global end of trial date
    27 Apr 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 May 2025
    First version publication date
    10 May 2025
    Other versions
    Summary report(s)
    		 MPNSG_02-12_Final_report_BfArM_22Apr2025_final_version

    Trial information

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    Trial identification
    Sponsor protocol code
    POMINC(MPNSG02-12)
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01644110
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University Hospital of Ulm
    Sponsor organisation address
    Albert-Einstein-Allee 23, Ulm, Germany, 89081
    Public contact
    Clinical trials office IM III, University Hospital of Ulm, +49 73150045901, mpnsg.innere3@uniklinik-ulm.de
    Scientific contact
    Clinical trials office IM III, University Hospital of Ulm, +49 73150045901, mpnsg.innere3@uniklinik-ulm.de
    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
    03 Dec 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Apr 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Apr 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • To evaluate the clinical efficacy of ruxolitinib and pomalidomide combination therapy in primary and secondary MF patients based on the consensus criteria of the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) (Tefferi A et al, 2006), extended by the criterion RBC-transfusion independence (RBC-TI) (Gale RP et al, 2011; Gale RP et al, 2012).
    Protection of trial subjects
    Safety was assessed by evaluation the following: reported adverse events, clinical laboratory test results, vital signs measurements, ECG findings, chest X-ray, sonographic assessment of the spleen, physical examination findings, monitoring of concomitant medications. For each safety parameter, all findings whether normal or abnormal were recorded in the CRF.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Aug 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 95
    Worldwide total number of subjects
    95
    EEA total number of subjects
    95
    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)
    17
    From 65 to 84 years
    77
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 First patient in: 19 Aug 2013; Last patient in: 27 April 2021; last patient out: 27 April 2024; Interruption after 6 patients in April 2014 for safety analysis. Restart of recruitment in July 2014. 2nd interruption in February 2017 until approval of amended protocol version 2.0. Restart of recruitment in August 2017.

    Pre-assignment
    Screening details
    		 Diagnosis of myeloproliferative neoplasms (de novo or secondary (post PV or post ET)), anemia with hemoglobin < 10g/dl or transfusion-dependent anemia, splenomegaly > 11cm total diameter and/or leukoerythroblastosis, ECOG < 3

    Pre-assignment period milestones
    Number of subjects started
    		 95
    Number of subjects completed
    		 92

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Protocol deviation: 3
    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1
    Arm description
    		 Treatment started for all patients with a combination therapy of pomalidomide of 0,5 mg once daily and ruxolitinib 10 mg twice daily. Pomalidomide could not be escalated or reduced (only discontinued in case of toxicities), but ruxolitinib was allowed to escalate after 4 weeks if platelet count was stable or increasing. Increase was allowed by 5 mg twice daily but the total dose of ruxolitinib may never exceed 25 mg twice daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pomalidomide
    Investigational medicinal product code
    Other name
    Imnovid
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 capsule of 0,5 mg per day for 12 cycles

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    Jakavi
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    2 capsules of 5 mg twice daily at treatment start, escalation of 5 mg twice daily allowed after 4 weeks if platelet counts stable or increasing, maximum dosage 25 mg twice daily. For 12 cycles

    Arm title
    		 Cohort 2
    Arm description
    		 Treatment started for all patients with a combination therapy of pomalidomide of 0,5 mg once daily and ruxolitinib 10 mg twice daily. For Pomalidomide dose escalation is intended as follows: cycles 1-3 0,5 mg once daily; cycles 4-6 1 mg once daily; starting cycle 7 2 mg once daily (reduction/discontinuation allowed in case of toxicities). Ruxolitinib was allowed to escalate after 4 weeks if platelet count was stable or increasing. Increase was allowed by 5 mg twice daily but the total dose of ruxolitinib may never exceed 25 mg twice daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pomalidomide
    Investigational medicinal product code
    Other name
    Imnovid
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 capsule of 0,5 mg (cycles 1-3), 1 mg (cycles 4-6) or 2 mg (start in cycle 7) per day for 12 cycles

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    Jakavi
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    2 capsules of 5 mg twice daily at treatment start, escalation of 5 mg twice daily allowed after 4 weeks if platelet counts stable or increasing, maximum dosage 25 mg twice daily. For 12 cycles

    Number of subjects in period 1 [1]
    		Cohort 1 Cohort 2
    Started
    39
    53
    Completed
    27
    31
    Not completed
    12
    22
         Adverse event, serious fatal
    3
    3
         Consent withdrawn by subject
    3
    6
         Adverse event, non-fatal
    1
    6
         Progress of underlying disease
    3
    1
         Transplantation
    1
    -
         Lack of efficacy
    1
    6
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 95 patients started with screening but only 92 were included into the treatment arms. 3 patients were screening failure due to protocol deviation.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    		 Treatment started for all patients with a combination therapy of pomalidomide of 0,5 mg once daily and ruxolitinib 10 mg twice daily. Pomalidomide could not be escalated or reduced (only discontinued in case of toxicities), but ruxolitinib was allowed to escalate after 4 weeks if platelet count was stable or increasing. Increase was allowed by 5 mg twice daily but the total dose of ruxolitinib may never exceed 25 mg twice daily.

    Reporting group title
    Cohort 2
    Reporting group description
    		 Treatment started for all patients with a combination therapy of pomalidomide of 0,5 mg once daily and ruxolitinib 10 mg twice daily. For Pomalidomide dose escalation is intended as follows: cycles 1-3 0,5 mg once daily; cycles 4-6 1 mg once daily; starting cycle 7 2 mg once daily (reduction/discontinuation allowed in case of toxicities). Ruxolitinib was allowed to escalate after 4 weeks if platelet count was stable or increasing. Increase was allowed by 5 mg twice daily but the total dose of ruxolitinib may never exceed 25 mg twice daily.

    Reporting group values
    		 Cohort 1 Cohort 2 Total
    Number of subjects
    		 39 53 92
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 7 10 17
        From 65-84 years
    		 32 42 74
        85 years and over
    		 0 1 1
    Age continuous
    Units: years
        median (full range (min-max))
    		 72 (49 to 83) 70 (52 to 86) -
    Gender categorical
    Units: Subjects
        Female
    		 17 21 38
        Male
    		 22 32 54
    Type of myelofibrosis
    Units: Subjects
        Primary MF
    		 30 34 64
        Secondary MF
    		 9 18 27
        Unclassified MF
    		 0 1 1
    Bone marrow fibrosis grade
    Units: Subjects
        Grade 0
    		 0 1 1
        Grade 1
    		 5 4 9
        Grade 2
    		 14 25 39
        Grade 3
    		 15 20 35
        Missing
    		 5 3 8
    ECOG
    Units: Subjects
        ECOG 0
    		 12 25 37
        ECOG 1
    		 25 25 50
        ECOG 2
    		 1 3 4
        Missing
    		 1 0 1
    Pretreated
    Pretreatment with any medications for myelofibrosis
    Units: Subjects
        yes
    		 22 33 55
        no
    		 17 20 37
    Pretreated with Ruxolitinib
    Units: Subjects
        yes
    		 6 23 29
        no
    		 33 30 63
    RBC transfusion dependent
    Units: Subjects
        yes
    		 10 19 29
        no
    		 29 34 63
    JAK2V617F Mutation
    Is a JAK2V617F Mutation available?
    Units: Subjects
        yes
    		 28 25 53
        no
    		 11 28 39
    MPL Mutation
    Is a MPM Mutation available?
    Units: Subjects
        yes
    		 3 8 11
        no
    		 36 45 81
    CALR Mutation
    Is a CALR Mutation available?
    Units: Subjects
        yes
    		 8 14 22
        no
    		 30 39 69
        Missing
    		 1 0 1
    Baseline DIPSS
    Units: Subjects
        Low
    		 1 0 1
        Intermediate - 1
    		 6 5 11
        Intermediate - 2
    		 27 39 66
        High
    		 5 9 14
    Any high risk mutation
    Is there any high risk mutation available (ASXL1, EZH2, SRSF2, IDH1+2, U2AF1, TP53)?
    Units: Subjects
        yes
    		 25 31 56
        no
    		 14 22 36
    ASXL1 Mutation
    Units: Subjects
        Yes
    		 16 22 38
        No
    		 23 31 54
    EZH2 Mutation
    Units: Subjects
        Yes
    		 4 7 11
        No
    		 35 46 81
    SRSF2 Mutation
    Units: Subjects
        Yes
    		 9 13 22
        No
    		 30 40 70
    IDH2 Mutation
    Units: Subjects
        Yes
    		 1 7 8
        No
    		 38 46 84
    U2AF1 Mutation
    Units: Subjects
        Yes
    		 5 7 12
        No
    		 34 46 80
    TP53 Mutation
    Units: Subjects
        Yes
    		 3 1 4
        No
    		 36 52 88
    Baseline spleen ultrasound
    Units: cm
        median (full range (min-max))
    		 17.9 (12.6 to 28.0) 17.0 (11.4 to 36.0) -
    Baseline spleen palpation
    Units: cm
        median (full range (min-max))
    		 5.0 (0 to 22.0) 3.0 (0 to 22.0) -
    Baseline hemoglobin value
    Units: g/dl
        median (full range (min-max))
    		 8.6 (5.4 to 11.7) 8.6 (5.9 to 10.8) -
    MPN SAF Baseline
    Mean values of selected questions of the Quality of Life Questionnare MPN-SAF.
    Units: Points
        arithmetic mean (standard deviation)
    		 2.98 ( 1.68 ) 2.62 ( 1.82 ) -
    Baseline thrombocytes value
    Units: Giga/l
        median (full range (min-max))
    		 249 (88 to 787) 247 (86 to 1240) -
    MIPSS
    Mutation-enhanced international prognostic score system
    Units: points
        median (full range (min-max))
    		 3 (1 to 3) 3 (1 to 3) -

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    		 Treatment started for all patients with a combination therapy of pomalidomide of 0,5 mg once daily and ruxolitinib 10 mg twice daily. Pomalidomide could not be escalated or reduced (only discontinued in case of toxicities), but ruxolitinib was allowed to escalate after 4 weeks if platelet count was stable or increasing. Increase was allowed by 5 mg twice daily but the total dose of ruxolitinib may never exceed 25 mg twice daily.

    Reporting group title
    Cohort 2
    Reporting group description
    		 Treatment started for all patients with a combination therapy of pomalidomide of 0,5 mg once daily and ruxolitinib 10 mg twice daily. For Pomalidomide dose escalation is intended as follows: cycles 1-3 0,5 mg once daily; cycles 4-6 1 mg once daily; starting cycle 7 2 mg once daily (reduction/discontinuation allowed in case of toxicities). Ruxolitinib was allowed to escalate after 4 weeks if platelet count was stable or increasing. Increase was allowed by 5 mg twice daily but the total dose of ruxolitinib may never exceed 25 mg twice daily.

    Subject analysis set title
    Intention-to-treat
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Includes all patients who received the study medication at least once.

    Primary: Response after 12 cycles

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    End point title
    		 Response after 12 cycles
    End point description
    Response was defined according to the IWG-MRT criteria (including complete remission, partial remission, clinical improvement), stable disease (Tefferi A et al, 2006), and red cell transfusion according to Gale et al 2010 and 2011, also progressive disease, relapse disease
    End point type
    Primary
    End point timeframe
    The end point disease response was examined at the end of each cycle until at least cycle 12.
    End point values
    		 Cohort 1 Cohort 2
    Number of subjects analysed
    39
    53
    Units: Subjects
        Complete remission
    0
    0
        Partial remission
    1
    0
        Clinical improvement
    6
    4
        Progressive disease
    1
    0
        Relapse disease
    2
    0
        Red blood cell transfusion dependent
    4
    6
        Red blood cell transfusion independent
    1
    2
        Clinical benefit
    0
    16
        Missing
    13
    23
        Stable disease
    11
    2
    Statistical analysis title
    		 Rate of response
    Statistical analysis description
    For cohort 1, response was defined as complete remission, partial remission, clinical improvement and red blood cell transfusion independency. For cohort 2, response was defined as complete remission, partial remission, clinical improvement and red blood cell transfusion independency, stable disease and clinical improvement.
    Comparison groups
    Cohort 2 v Cohort 1
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    Method
    		 Binomialtest
    Parameter type
    		 Estimated response rate
    Point estimate
    0.453
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 0.335
         upper limit
    		 -
    Notes
    [1] - For cohort 1, Simon's 2 stage design was used for analysis. The estimated response rate was 0.205 with one-sided 90% CI [0.123, 1]. According to amendment 2, additional 53 subjects was included as cohort 2 to decide whether the proportion responding, P, is less than or equal to 0.300 (null hypothesis) or greater than or equal to 0.500 (alternative). For cohort 2, a binomial test was used.

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    End point type
    Secondary
    End point timeframe
    Overall Survival: Number of patients and events by cohort with median survival time in months.
    End point values
    		 Cohort 1 Cohort 2
    Number of subjects analysed
    39
    53
    Units: months
        median (confidence interval 95%)
    38.4 (29.8 to 100)
    60.8 (29.8 to 999)
    No statistical analyses for this end point

    Secondary: Progression free survival

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    End point title
    		 Progression free survival
    End point description
    End point type
    Secondary
    End point timeframe
    Progression free survival: Number of patients and events by cohort with median survival time in months
    End point values
    		 Cohort 1 Cohort 2
    Number of subjects analysed
    39
    53
    Units: months
        median (confidence interval 95%)
    29.8 (16.4 to 43)
    34.3 (21.2 to 999)
    No statistical analyses for this end point

    Secondary: Duration or response

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    End point title
    		 Duration or response
    End point description
    End point type
    Secondary
    End point timeframe
    Duration of response from first response to loss of response (if occurred) or until end-of-FU ( if no loss occurred)
    End point values
    		 Cohort 1 Cohort 2
    Number of subjects analysed
    39
    53
    Units: cycles
        median (full range (min-max))
    15 (8 to 126)
    9 (2 to 77)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from Informed Consent signature up to 28 days after last study drug administration or until all drug-related toxicities had been resolved, whichever was later.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    3.0
    Reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    		 All patients treated cohort 1

    Reporting group title
    Cohort 2
    Reporting group description
    		 All patients treated in cohort 2

    Serious adverse events
    		 Cohort 1 Cohort 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    30 / 39 (76.92%)
    35 / 53 (66.04%)
         number of deaths (all causes)
    6
    6
         number of deaths resulting from adverse events
    6
    6
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    6 / 39 (15.38%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Fibrosarcoma
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant melanoma
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal adenocarcinoma
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Second primary malignancy
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vasculitis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Surgical and medical procedures
    Breast operation
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint arthroplasty
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Knee arthroplasty
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Sudden cardiac death
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Chest pain
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Condition aggravated
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    3 / 39 (7.69%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pain
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Reproductive system and breast disorders
    Acquired hydrocele
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haemorrhage
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Myocardial infarction
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac valve disease
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiorenal syndrome
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Endocarditis fibroplastica
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachyarrhythmia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral ischaemia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dizziness
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraplegia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Peripheral sensory neuropathy
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic haemorrhage
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenomegaly
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Spontaneous haematoma
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diarrhoea
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Large intestine perforation
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatotoxicity
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Soft tissue necrosis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis infective
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cystitis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasopharyngitis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral viral infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    5 / 39 (12.82%)
    6 / 53 (11.32%)
         occurrences causally related to treatment / all
    0 / 5
    4 / 7
         deaths causally related to treatment / all
    0 / 2
    1 / 1
    Sepsis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Septic shock
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Skin infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary trat infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid retention
    alternative dictionary used: MedDRA 27.0
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Cohort 1 Cohort 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    38 / 39 (97.44%)
    53 / 53 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Dermatology - Other (Basal cell carcinoma)
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    3
    1
    Dermatology - Other (Spinaliom)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Secondary Malignancy (possibly related to cancer treatment)
    Additional description: basal cell carcinoma
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Sexual - Other (cyst right ovary)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Vascular disorders
    Hematoma
         subjects affected / exposed
    3 / 39 (7.69%)
    5 / 53 (9.43%)
         occurrences all number
    7
    6
    Hemorrhage - Other (defecation - black dyed)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Hemorrhage - Other (eye)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Hemorrhage - Other (Gums)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Hemorrhage - Other (tongue)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Hemorrhage -Other (spitting of blood)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Hemorrhage pulmonary - Nose
         subjects affected / exposed
    4 / 39 (10.26%)
    2 / 53 (3.77%)
         occurrences all number
    9
    2
    Hemorrhage with surgery
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Hemorrhage, Gl - Oral cavity
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Hemorrhage, GU
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Thrombosis/embolism (vascular access)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Thrombosis/thrombus/embolism
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Vascular - Other (atherosklerotic artery on both sides)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Vascular - Other (circumference increase leg left)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Vasculitis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Vein injury - Extremity (lower)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Constitutional Symptoms - Other (exhaustion)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Constitutional Symptoms - Other (General disorder)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Constitutional Symptoms - Other (physical ability decreased)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Constitutional Symptoms - Other (reduced constitutional behavior)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Constitutional Symptoms - Other (reduced exercise capacity)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Constitutional Symptoms - Other (Reduced general condition)
         subjects affected / exposed
    4 / 39 (10.26%)
    0 / 53 (0.00%)
         occurrences all number
    4
    0
    Constitutional Symptoms - Other (Vitamin D3 deficiency)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Constitutional Symptoms - Other (Weakness)
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Fatigue
         subjects affected / exposed
    16 / 39 (41.03%)
    12 / 53 (22.64%)
         occurrences all number
    24
    13
    Fever
         subjects affected / exposed
    3 / 39 (7.69%)
    8 / 53 (15.09%)
         occurrences all number
    5
    14
    Insomnia
         subjects affected / exposed
    4 / 39 (10.26%)
    2 / 53 (3.77%)
         occurrences all number
    4
    2
    Rigors/chills
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences all number
    3
    1
    Sweating
         subjects affected / exposed
    3 / 39 (7.69%)
    3 / 53 (5.66%)
         occurrences all number
    4
    3
    Weight gain
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    2
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Allergy - Other (vaccination reaction)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    1 / 39 (2.56%)
    3 / 53 (5.66%)
         occurrences all number
    1
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 39 (17.95%)
    8 / 53 (15.09%)
         occurrences all number
    8
    12
    Dyspnea
         subjects affected / exposed
    12 / 39 (30.77%)
    21 / 53 (39.62%)
         occurrences all number
    19
    31
    Hypoxia
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    2
    Nasal/paranasal reactions
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    2
    Pain - Chest/thorax NOS
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Pain - Other (Chest wall)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pain | Pulmonary/Upper Respiratory: Chest/thorax NOS
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    2
    Pain | Pulmonary/Upper Respiratory: Throat/pharynx/larynx
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pleural effusion
         subjects affected / exposed
    3 / 39 (7.69%)
    1 / 53 (1.89%)
         occurrences all number
    3
    1
    Pulmonary - Other (breath sound)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pulmonary - Other (bronchitis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pulmonary - Other (influenza)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pulmonary - Other (Pneumonia NOS)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Cardiac General - Other (Cardiac decompensation)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Valvular heart disease
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Edema: trunk/genital
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Intraop injury - Artery-aorta
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Left ventricular systolic dysfunction
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Supraventricular arrhythmia - Atrial fibrillation
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Cardiac General - Other (cardiac insufficiency)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Cardiac General - Other (coronary artery disease)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Cardiac General - Other (Edema pulmonary)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Cardiac General - Other (Edema)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Cardiac General - Other (heart insufficiency)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Conduction abnormality - AV block second degree
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pain | Cardiavascular: Cardiac/heart
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Palpitations
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Supraventricular arrhythmia - Sinus bradycardia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Cardiac Arrhythmia - Other (Arrhythmia)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Cardiac General - Other (cardiopulmonal congestion)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Cardiac General - Other (increased heart rate)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Cardiac General - Other (drop in blood pressure)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Conduction abnormality - AV Block-Third degree (Complete AV Block)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Edema: Head and neck
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Hypotension
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Edema: limb
         subjects affected / exposed
    1 / 39 (2.56%)
    4 / 53 (7.55%)
         occurrences all number
    1
    5
    Hypertension
         subjects affected / exposed
    4 / 39 (10.26%)
    3 / 53 (5.66%)
         occurrences all number
    4
    3
    Pulmonary hypertension
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Apnea
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    2
    Confusion
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Dizziness
         subjects affected / exposed
    11 / 39 (28.21%)
    10 / 53 (18.87%)
         occurrences all number
    16
    11
    Mood alteration - Depression
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Mood alteration
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Neurology - Other (Concentration problem)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    2
    Neurology - Other (Dysesthesia)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Neurology - Other (Panic attack)
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Neurology - Other (Paresthesia)
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Neurology - Other (Polyneuropathy)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Neurology - Other (speaking disorder)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Neurology - Other (Spinal disc herniation)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Neurology - Other (Tingling in feet)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Neuropathy - sensory
         subjects affected / exposed
    3 / 39 (7.69%)
    10 / 53 (18.87%)
         occurrences all number
    3
    10
    Pain | Neurology: Head/headache
         subjects affected / exposed
    6 / 39 (15.38%)
    5 / 53 (9.43%)
         occurrences all number
    8
    7
    Pain | Neurology: Neuralgia/peripheral nerve
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Syncope (fainting)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Tremor
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    4
    Blood and lymphatic system disorders
    Hemoglobin
         subjects affected / exposed
    17 / 39 (43.59%)
    23 / 53 (43.40%)
         occurrences all number
    21
    29
    Platelets
         subjects affected / exposed
    6 / 39 (15.38%)
    8 / 53 (15.09%)
         occurrences all number
    9
    10
    Blood - Other (leukocytosis)
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 53 (3.77%)
         occurrences all number
    4
    2
    Blood - Other (Splenomegaly)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Hemolysis
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Coagulation - Other (von Willebrandt sydrome type 2)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Iron overload
         subjects affected / exposed
    1 / 39 (2.56%)
    4 / 53 (7.55%)
         occurrences all number
    1
    4
    Neutrophils
         subjects affected / exposed
    1 / 39 (2.56%)
    8 / 53 (15.09%)
         occurrences all number
    1
    8
    Blood - Other (Thrombocytosis)
         subjects affected / exposed
    3 / 39 (7.69%)
    3 / 53 (5.66%)
         occurrences all number
    4
    3
    Blood - Other (eosinophilia)
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Blood - Other (Blasts)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    2
    Blood - Other (Hematocrit decreased)
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    3
    Coagulation - Other (Coagulation disorder)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    INR
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Leukocytes
         subjects affected / exposed
    0 / 39 (0.00%)
    4 / 53 (7.55%)
         occurrences all number
    0
    4
    Lymphatics - Other (Lymphnodes)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Blood - Other (red blood cells decreased)
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    2
    Ear and labyrinth disorders
    Auditory/Ear - Other (Ear noises
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Hearing (without monitoring program)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pain | Auditory/Ear: External ear
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Tinnitus
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Eye disorders
    Blurred vision
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    2
    Dry eye
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Glaucoma
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Ocular - Other (Eye irritation)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Ocular - Other (Herpes eye)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Ocular - Other (Swollen eyes)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Ocular - Other (Swollen tear sac)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Ocular surface disease
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Watery eye
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Anorexia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Ascites
         subjects affected / exposed
    3 / 39 (7.69%)
    1 / 53 (1.89%)
         occurrences all number
    3
    1
    Colitis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    6 / 39 (15.38%)
    12 / 53 (22.64%)
         occurrences all number
    8
    12
    Diarrhea
         subjects affected / exposed
    9 / 39 (23.08%)
    15 / 53 (28.30%)
         occurrences all number
    11
    21
    Distension
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Dry mouth
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Dysphagia
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Flatulence
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    3
    Gastritis
         subjects affected / exposed
    1 / 39 (2.56%)
    5 / 53 (9.43%)
         occurrences all number
    1
    5
    Gastrointestinal - Other (loss of appetite)
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences all number
    2
    1
    Gastrointestinal - Other (abdominal problems)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal - Other (Condylomas)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    2
    Gastrointestinal - Other (Gastroenteritis)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Gastrointestinal - Other (unspecific symptoms)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Heartburn
         subjects affected / exposed
    2 / 39 (5.13%)
    7 / 53 (13.21%)
         occurrences all number
    2
    7
    Mucositis (clinical exam) - Pharynx
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Mucositis (clinical exam) - Oral cavity
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Nausea
         subjects affected / exposed
    5 / 39 (12.82%)
    5 / 53 (9.43%)
         occurrences all number
    5
    6
    Pain | Gastrointestinal: Abdomen NOS
         subjects affected / exposed
    7 / 39 (17.95%)
    3 / 53 (5.66%)
         occurrences all number
    13
    9
    Pain | Gastrointestinal: Dental/teeth/periodontal
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Pain | Gastrointestinal: Oral cavity
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Pain | Gastrointestinal: stomach
         subjects affected / exposed
    1 / 39 (2.56%)
    4 / 53 (7.55%)
         occurrences all number
    3
    4
    Taste alteration
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Teeth
         subjects affected / exposed
    2 / 39 (5.13%)
    3 / 53 (5.66%)
         occurrences all number
    2
    4
    Teeth development
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    4 / 39 (10.26%)
    7 / 53 (13.21%)
         occurrences all number
    4
    9
    Hepatobiliary disorders
    Hepatobiliary - Other (Steatosis)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Pain | Hepatobiliary/Pancreas: Liver
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 53 (3.77%)
         occurrences all number
    1
    2
    Bruising
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Decubitus
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Dermatology - Other (perioral efflorescence)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Dermatology - Other (diaper rash)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Dermatology - Other (eczema)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Dermatology - Other (Erysipel face)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Dermatology - Other (excision of skin change)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Dermatology - Other (furuncle right buttock)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Dermatology - Other (Herpes zoster)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Dermatology - Other (Skin changes)
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    3
    Dermatology - Other (skin lesion)
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Dermatology - Other (swelling of lower leg)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Dry skin
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    3
    Flushing
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Injection site reaction
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    3 / 39 (7.69%)
    2 / 53 (3.77%)
         occurrences all number
    4
    2
    Rash
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 53 (3.77%)
         occurrences all number
    2
    3
    Ulceration
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Cystitis
         subjects affected / exposed
    3 / 39 (7.69%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Pain - Renal/Genitourinary - Kidney
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Renal - Other (Chronic kidney disease)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Renal - Other (chronic renal insufficiency)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Renal - Other (fluid retention)
         subjects affected / exposed
    7 / 39 (17.95%)
    9 / 53 (16.98%)
         occurrences all number
    9
    10
    Renal - Other (fluid retention/ edema)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Renal - Other (Prostata adenoma)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Renal - Other (recurrent dysuria)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Renal - Other (Renal stricture)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    renal - other (urinary obstruction)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Renal failure
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences all number
    2
    1
    Urinary frequency
         subjects affected / exposed
    1 / 39 (2.56%)
    3 / 53 (5.66%)
         occurrences all number
    2
    4
    Urinary retention
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Endocrine disorders
    Endocrine - Other (partially hemorrhagic cyst)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Endocrine - Other (Struma multinodosa)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Hot flashes
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Hypothyroidism
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    3
    Musculoskeletal and connective tissue disorders
    Fracture
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 53 (3.77%)
         occurrences all number
    1
    2
    Joint - function
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Muscle weakness
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Musculoskeletal - Other (arthrosis left knee)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal - Other (bone pain, hip pain)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Musculoskeletal - Other (Bursitis)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Musculoskeletal - Other (Cervicobrachialgie)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal - Other (coxarthrosis)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal - Other (Cramps calves)
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal - Other (Cramps)
         subjects affected / exposed
    15 / 39 (38.46%)
    14 / 53 (26.42%)
         occurrences all number
    20
    16
    Musculoskeletal - Other (disc herniation)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal - Other (hernia)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Musculoskeletal - Other (Lockjaw)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Musculoskeletal - Other (muscle tension neck)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal - Other (muscle tensions)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal - Other (spasms)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal - Other (Swelling ankle)
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    2
    Musculoskeletal - Other (Tendon rupture)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Musculoskeletal - Other (tension right shoulder)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pain - Other (Flank right)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Pain - Other (Groin)
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Pain - Other (jaw)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Pain - Other (left axilla)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Pain - Other (leg)
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Pain | Musculoskeletal: Back
         subjects affected / exposed
    5 / 39 (12.82%)
    8 / 53 (15.09%)
         occurrences all number
    7
    8
    Pain | Musculoskeletal: Bone
         subjects affected / exposed
    5 / 39 (12.82%)
    4 / 53 (7.55%)
         occurrences all number
    11
    4
    Pain | Musculoskeletal: Buttock
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Pain | Musculoskeletal: Extremity-limb
         subjects affected / exposed
    5 / 39 (12.82%)
    1 / 53 (1.89%)
         occurrences all number
    9
    1
    Pain | Musculoskeletal: Joint
         subjects affected / exposed
    8 / 39 (20.51%)
    14 / 53 (26.42%)
         occurrences all number
    8
    16
    Pain | Musculoskeletal: Muscle
         subjects affected / exposed
    5 / 39 (12.82%)
    3 / 53 (5.66%)
         occurrences all number
    10
    3
    Pain | Musculoskeletal: Neck
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    Flu-like syndrome
         subjects affected / exposed
    4 / 39 (10.26%)
    1 / 53 (1.89%)
         occurrences all number
    6
    1
    Infection - Other (Abscess)
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    3
    Infection - Other (aspiration pneumonia)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection - Other (common cold)
         subjects affected / exposed
    8 / 39 (20.51%)
    6 / 53 (11.32%)
         occurrences all number
    11
    10
    Infection - Other (COVID 19 Infection)
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Infection - Other (erysipel)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection - Other (Follikulitis)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection - Other (foot)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Infection - Other (General, Blood)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Infection - Other (Herpes zoster)
         subjects affected / exposed
    4 / 39 (10.26%)
    2 / 53 (3.77%)
         occurrences all number
    5
    3
    Infection - Other (Left digitus medius)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection - Other (phlegmon)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection - Other (Pneumonia)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection - Other (Sepsis)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection - Other (Skin)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Infection - Other (sore throat)
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Infection - Other (Urosepsis)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection - Other (wound)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Infection with grade 3 or 4 neutrophils- Liver
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection with grade 3 or 4 neutrophils- pharynx
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Infection with grade 3 or 4 neutrophils
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection with grade 3 or 4 neutrophils- Urinary tract NOS
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection with normal ANC
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection with normal ANC - Upper airway NOS
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection with unknown ANC - Bronchus
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Infection with unknown ANC - pharynx
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Infection with unknown ANC - Upper airway NOS
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection with unknown ANC - Urinary tract NOS
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Infection| Dermatology/Skin: Lip/perioral
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Infection| Gastrointestinal: Abdomen NOS
         subjects affected / exposed
    5 / 39 (12.82%)
    6 / 53 (11.32%)
         occurrences all number
    6
    6
    Infection| Gastrointestinal: Dental-tooth
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Infection| Gastrointestinal: Oral cavity-gums (gingivitis)
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection| Musculoskeletal: Joint
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Infection| Ocular: Conjunctiva
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences all number
    2
    1
    Infection| Ocular: Eye NOS
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection| Pulmonary/Upper Respiratory: Bronchus
         subjects affected / exposed
    7 / 39 (17.95%)
    3 / 53 (5.66%)
         occurrences all number
    8
    3
    Infection| Pulmonary/Upper Respiratory: Lung (pneumonia)
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    3
    Infection| Pulmonary/Upper Respiratory: Pharynx
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection| Pulmonary/Upper Respiratory: Sinus
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Infection| Pulmonary/Upper Respiratory: Upper aerodigestive NOS
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Infection| Pulmonary/Upper Respiratory: Upper airway NOS
         subjects affected / exposed
    3 / 39 (7.69%)
    13 / 53 (24.53%)
         occurrences all number
    6
    14
    Infection| Renal/Genitourinary: Bladder (urinary)
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Infection| Renal/Genitourinary: Prostate
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Infection| Renal/Genitourinary: Urinary tract NOS
         subjects affected / exposed
    5 / 39 (12.82%)
    8 / 53 (15.09%)
         occurrences all number
    6
    9
    Infection| Sexual/Reproductive Function: Pelvis NOS
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    ALT
         subjects affected / exposed
    4 / 39 (10.26%)
    1 / 53 (1.89%)
         occurrences all number
    5
    1
    AST
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences all number
    2
    1
    Cholesterol
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Creatinine
         subjects affected / exposed
    9 / 39 (23.08%)
    2 / 53 (3.77%)
         occurrences all number
    9
    3
    GGT
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Hyperkalemia
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 53 (1.89%)
         occurrences all number
    2
    1
    Hyperuricemia
         subjects affected / exposed
    8 / 39 (20.51%)
    6 / 53 (11.32%)
         occurrences all number
    9
    6
    Hypoalbuminemia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    Hypocalcemia
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    Hypokalemia
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Metabolic/Lab - Other (Hyperphospatemia)
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    Metabolic/Lab - Other (Iron deficiency)
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    2
    Metabolic/Lab - Other (LDH increase)
         subjects affected / exposed
    1 / 39 (2.56%)
    3 / 53 (5.66%)
         occurrences all number
    1
    3
    Metabolic/Lab - Other (Urea high)
         subjects affected / exposed
    3 / 39 (7.69%)
    0 / 53 (0.00%)
         occurrences all number
    4
    0
    Metabolic/Lab - Other (Vitamin D deficiency)
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Dec 2013
    Urgent Amendment: Ruxolitinib was initially dispensed in bottles. This urgent amendment was necessary as Ruxolitinib was not available in bottles anymore but only in blisters. The urgent amendment was implemented in protocol version 1.4
    16 Apr 2014
    Amendment 1.4 (07.01.2024): Exclusion Critera added "Patient treatment with Ruxolitinib within a 14 days time period before Screening phase"; Implementation of tuberculosis tests; bone marrow biopsy and aspiration obtained at baseline, end of cycle 6, end of cycle 12 (biopsy: reference lab Hannover and Freiburg, aspiration: reference lab Ulm); Ruxolitinib dispensed in blisters (see also urgent amendment); parameter haptoglobin added.
    06 Jun 2017
    Amendment V 2.0 (28.03.2017): cohort 2 implemented: Pomaldomid 0,5 mg for 3 cycles, afterwards 1 mg for 3 cycles, starting cycle 7 2 mg; no change for Ruxolitinib; sample size increased: cohort 2 intended patient sample size n=53; study end changed to May 2022; exporative response criteria clinical benefit added; pregnancy prevention plan updated; Pomalidomid will be dispensed in wallets, not in bottles anymore.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    25 Mar 2014
    The POMINC study was interrupted for a safety analysis after enrollment of 6 patients and an observation period of each patient of at least one cycles (28 days) on 25-Mar-2014. This was outlined in the protocol (12.3.4). As the LKP, the trial coordinator, the statistician and the DSMB didn't have any safety concerns the study restarted recruitment on 02-Jul-2014
    02 Jul 2014

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

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