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    Clinical Trial Results:
    A Phase 2, International, Multicenter, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy and Safety of CC-486 (oral azacitidine) Alone and in Combination With Durvalumab (MEDI4736) in Subjects With Myelodysplastic Syndromes Who Fail to Achieve an Objective Response to Treatment With Azacitidine for Injection or Decitabine

    Summary
    EudraCT number
    2014-002675-29
    Trial protocol
    FR   GB   BE   ES   DE   PL   IT  
    Global end of trial date
    14 Sep 2023

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

    Trial information

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    Trial identification
    Sponsor protocol code
    CC-486-MDS-006
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02281084
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium,
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Sep 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Sep 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluate the safety and efficacy of oral azacitidne (CC-486) twice daily (BID) in subjects with myelodysplastic syndromes who failed to achieve an objective response post injectable hypomethylating agent (iHMA) treatment
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    06 Jul 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 5
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    United States: 31
    Worldwide total number of subjects
    65
    EEA total number of subjects
    26
    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)
    6
    From 65 to 84 years
    56
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    Participants were randomized at 33 sites globally. The sites were located in: Australia (3), Europe (18) and the United States (12).

    Pre-assignment
    Screening details
    Participants were eligible who did not respond to an adequate course of therapy with an injectable hypomethylating agent (iHMA - azacitidine or decitabine) or were unable to tolerate an iHMA following at least 3 months of attempted treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Stable Disease (SD) Cohort: Oral Azacitidine
    Arm description
    Participants were given oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    CC-486
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Arm title
    Progressive Disease (PD) Cohort: Oral Azacitidine
    Arm description
    Participants were given oral azacitidine 100 mg, 150mg, or 200mg tablets BID on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    CC-486
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Arm title
    Stable Disease Cohort: Oral Azacitidine and Durvalumab
    Arm description
    Participants received 100 mg oral azacitidine (AZA) tablets BID on days 1 to 14 or days 1 to 21 of each 28-day treatment cycle and durvalumab (Durva) 1500 mg by intravenous infusion on day 1 of each 28-day treatment cycle; participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Imfinzi, MEDI4736
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 1500 mg by IV infusion on Day 1 of each 28 day treatment cycle.

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    CC-486
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Arm title
    Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Arm description
    Participants received 100 mg oral azacitidine tablets BID on days 1 to 14 or days 1 to 21 of each 28-day treatment cycle and durvalumab 1500 mg by intravenous infusion on day 1 of each 28-day treatment cycle; participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Imfinzi, MEDI4736
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 1500 mg by IV infusion on Day 1 of each 28 day treatment cycle.

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    CC-486
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Number of subjects in period 1
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Started
    32
    22
    6
    5
    Completed
    3
    1
    1
    0
    Not completed
    29
    21
    5
    5
         Adverse event, serious fatal
    21
    18
    3
    5
         Consent withdrawn by subject
    2
    2
    -
    -
         Adverse event, non-fatal
    1
    -
    -
    -
         Site Closure by Sponsor
    5
    1
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Stable Disease (SD) Cohort: Oral Azacitidine
    Reporting group description
    Participants were given oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Reporting group title
    Progressive Disease (PD) Cohort: Oral Azacitidine
    Reporting group description
    Participants were given oral azacitidine 100 mg, 150mg, or 200mg tablets BID on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Reporting group title
    Stable Disease Cohort: Oral Azacitidine and Durvalumab
    Reporting group description
    Participants received 100 mg oral azacitidine (AZA) tablets BID on days 1 to 14 or days 1 to 21 of each 28-day treatment cycle and durvalumab (Durva) 1500 mg by intravenous infusion on day 1 of each 28-day treatment cycle; participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Reporting group title
    Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Reporting group description
    Participants received 100 mg oral azacitidine tablets BID on days 1 to 14 or days 1 to 21 of each 28-day treatment cycle and durvalumab 1500 mg by intravenous infusion on day 1 of each 28-day treatment cycle; participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Reporting group values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab Total
    Number of subjects
    32 22 6 5 65
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0
        Adults (18-64 years)
    2 2 3 0 7
        From 65-84 years
    29 18 3 5 55
        85 years and over
    1 2 0 0 3
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    73.9 ( 7.62 ) 75.1 ( 7.56 ) 70.0 ( 7.21 ) 72.4 ( 5.55 ) -
    Sex: Female, Male
    Units: Participants
        Female
    12 7 0 0 19
        Male
    20 15 6 5 46
    Race/Ethnicity, Customized
    Units: Subjects
        White
    28 18 6 5 57
        Black
    0 1 0 0 1
        Asian
    1 1 0 0 2
        Native Hawaiian or Other Pacific Islander
    0 1 0 0 1
        American Indian or Alaska Native
    0 0 0 0 0
        Other
    1 1 0 0 2
        Not Collected or Reported
    2 0 0 0 2
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    1 1 0 2 4
        Not Hispanic or Latino
    30 21 6 3 60
        Unknown
    1 0 0 0 1
    Myelodysplastic Syndrome (MDS) World Health Organization Classification 2008
    The World Health Organization (WHO) 2008 classification recognizes eight subtypes of MDS that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts (i.e., erythroid precursors with iron deposits surrounding the nucleus), presence of a monocytosis or a deletion 5q.
    Units: Subjects
        Refractory Anemia (RA) with Ringed Sideroblasts
    1 0 0 0 1
        Refractory Cytopenia with Multilineage Dysplasia
    11 2 1 0 14
        RA With Excess Blasts-1 (RAEB-1)
    10 6 1 2 19
        RA With Excess Blasts-2 (RAEB-2)
    8 11 4 3 26
        MDS Unclassified (MDS-U)
    1 3 0 0 4
        MDS Associated with Isolated del (5q)
    0 0 0 0 0
        Missing
    1 0 0 0 1
    International Prognostic Scoring System Risk Classification
    The international prognostic scoring system (IPSS) is a standard for risk assessment in primary myelodysplastic syndromes (MDS) that categorizes prognoses taking into account cytogenetics, cytopenias, blasts and blood counts. The IPSS prognostic subgroups consist of low-, intermediate-1-, intermediate-2-, and high-risk groups. The scale is 0-3.5 at 0.5 increments. Scores of 0=Low; 0.5-1.0=Int-1; 1.5-2.0=Int-2; 2.5-3.5=High risk which corresponds to poorer prognosis.
    Units: Subjects
        Low (0)
    4 2 0 0 6
        Intermediate 1 (0.5-1.0)
    12 5 1 2 20
        Intermediate (2) (1.0-2.0)
    7 7 4 2 20
        High (2) (≥ 2.5)
    8 8 1 1 18
        Unknown
    1 0 0 0 1
    French-American-British (FAB) Classification
    FAB is a classification system for five (5) subtypes of myelodysplastic syndrome that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts or a monocytosis.
    Units: Subjects
        Refractory Anemia (RA)
    6 2 0 0 8
        Refractory Anemia with Ringed Sideroblasts (RARS)
    6 1 1 0 8
        Refractory Anemia with Excess Blasts (RAEB)
    17 16 5 4 42
        RAEB in Transformation
    2 3 0 1 6
        Chronic Myelomonocytic Leukemia (CMML)
    0 0 0 0 0
        Missing
    1 0 0 0 1
    Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
    ECOG performance status is used by doctors and researchers to assess how a subject's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)
    Units: Subjects
        0 (Fully active)
    5 6 3 2 16
        1 (Restricted but Ambulatory)
    22 13 3 3 41
        2 (Ambulatory But Unable to Work)
    5 3 0 0 8
        3 (Limited Self-Care)
    0 0 0 0 0
        4 (Completely Disabled)
    0 0 0 0 0
        5 (Death)
    0 0 0 0 0
    Baseline Platelet Transfusion Status
    Baseline Platelet transfusion dependence is defined as ≥ 2 transfusions (in units) during the 56 days prior to treatment. Platelet transfusion independence is defined as 0 transfusions (in units) during the 56 days prior to treatment.
    Units: Subjects
        Dependent
    4 5 0 1 10
        Independent
    25 13 6 4 48
        Other
    3 4 0 0 7
    Baseline Red Blood Cell (RBC) Transfusion Status
    Baseline RBC Transfusion Dependence is defined as ≥ 4 transfusions (in units) during the 56 days prior to treatment. RBC transfusion independence is defined as 0 transfusions (in units) during the 56 days prior to treatment.
    Units: Subjects
        Dependent
    8 7 0 2 17
        Independent
    8 6 3 2 19
        Other
    16 9 3 1 29
    Average Red Blood Cell (RBC) Transfusion Requirement
    Documentation of all red blood cell transfusions received by the participant within 8 weeks (56 days) prior to the first dose of study drug.
    Units: units per 56 days
        median (full range (min-max))
    4.00 (0.00 to 10.0) 3.50 (0.0 to 7.0) 3.00 (0.0 to 7.0) 4.00 (0.0 to 15.0) -

    End points

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    End points reporting groups
    Reporting group title
    Stable Disease (SD) Cohort: Oral Azacitidine
    Reporting group description
    Participants were given oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Reporting group title
    Progressive Disease (PD) Cohort: Oral Azacitidine
    Reporting group description
    Participants were given oral azacitidine 100 mg, 150mg, or 200mg tablets BID on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Reporting group title
    Stable Disease Cohort: Oral Azacitidine and Durvalumab
    Reporting group description
    Participants received 100 mg oral azacitidine (AZA) tablets BID on days 1 to 14 or days 1 to 21 of each 28-day treatment cycle and durvalumab (Durva) 1500 mg by intravenous infusion on day 1 of each 28-day treatment cycle; participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Reporting group title
    Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Reporting group description
    Participants received 100 mg oral azacitidine tablets BID on days 1 to 14 or days 1 to 21 of each 28-day treatment cycle and durvalumab 1500 mg by intravenous infusion on day 1 of each 28-day treatment cycle; participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred.

    Primary: Overall Response Rate Based on the Modified International Working Group (IWG) 2006 Response Criteria for Myelodysplastic Syndrome (MDS)

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    End point title
    Overall Response Rate Based on the Modified International Working Group (IWG) 2006 Response Criteria for Myelodysplastic Syndrome (MDS) [1]
    End point description
    The overall response rate (ORR) was defined as the percentage of participants who achieved an objective response including: hematologic improvement (HI), partial remission (PR), complete remission (CR), or marrow complete remission (mCR). Hematologic response was defined as: • CR: ≤ 5% myeloblasts with normal maturation of all cell lines; peripheral blood (PB) shows: hemoglobin ≥11 g/dL, neutrophils ≥1.0x10^9/L, platelets ≥100x10^9/dL, blasts (0%) • PR: same as CR bone marrow (BM) shows blasts decreased by ≥ 50% over pre-treatment but still > 5%; cellularity and morphology not relevant • mCR: BM: ≤ 5% myeloblasts and decrease by ≥ 50% over pre-treatment PB, PB: if HI responses, noted in addition to mCR • HI: HI erythroid response (HI-E); HI neutrophil response (HI-N) ; HI platelet response (HI-P)
    End point type
    Primary
    End point timeframe
    Response was assessed every 2 cycles following treatment during the first 6 cycles, then every 3 cycles thereafter; median duration of treatment = 5.26 and 3.81 months for SD/PD for oral AZA arms respectively, and 1.84 months for AZA and Durva SD/PD arms
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not planned as per study plan.
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    6
    5
    Units: Percentage of Participants
        number (confidence interval 95%)
    6.3 (0.8 to 20.8)
    4.5 (0.1 to 22.8)
    16.7 (0.4 to 64.1)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Overall Survival

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    End point title
    Kaplan-Meier Estimate of Overall Survival
    End point description
    Overall survival (OS) was defined as the time from randomization to death from any cause, and was calculated using date of first dose and date of death, or date of last follow-up for censored subjects.
    End point type
    Secondary
    End point timeframe
    From first dose till death due to any cause (Up to 91 months)
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    6
    5
    Units: Months
        median (confidence interval 95%)
    17.00 (10.03 to 24.99)
    6.28 (4.50 to 15.19)
    14.70 (1.58 to 99999)
    14.56 (9.73 to 99999)
    No statistical analyses for this end point

    Secondary: Kaplan Meier Estimate of Time to Onset of First and Best Response

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    End point title
    Kaplan Meier Estimate of Time to Onset of First and Best Response
    End point description
    Time to onset of first response was defined as the time between the date of first investigational product (IP) dose and the earliest date any response (CR, PR, mCR, or HI) was first observed. Participants who did not achieve any defined response during the treatment period were censored at the date of treatment discontinuation, disease progression, or death, whichever occurred first. Best response is the best recorded response or treatment outcome from the start of the study treatment until the end of the study treatment taking into account the requirements for confirmation of response.
    End point type
    Secondary
    End point timeframe
    Response was assessed every 2 cycles following treatment during the first 6 cycles, then every 3 cycles thereafter; median duration of treatment = 5.26 and 3.81 months for SD/PD for oral AZA arms respectively, and 1.84 months for AZA and Durva SD/PD arms
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    6
    5
    Units: Months
    median (confidence interval 95%)
        Onset of First Response
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Onset of Best Response
    3.68 (2.10 to 99999)
    4.41 (1.68 to 99999)
    3.29 (1.64 to 99999)
    2.17 (1.64 to 99999)
    No statistical analyses for this end point

    Secondary: Kaplan Meier Estimate of Duration of First Response

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    End point title
    Kaplan Meier Estimate of Duration of First Response [2]
    End point description
    Duration of hematologic response and/or improvement was defined as the time from the date response or improvement was first observed to the date of documented relapse or disease progression as defined by the modified IWG 2006 criteria. Particpants who maintained hematologic response and/or improvement through the end of the treatment period were censored as the date of treatment discontinuation or death, whichever occurred first.
    End point type
    Secondary
    End point timeframe
    Response was assessed every 2 cycles following treatment during the first 6 cycles, then every 3 cycles thereafter; median duration of treatment = 5.26 and 3.81 months for SD/PD for oral AZA arms respectively, and 1.84 months for AZA and Durva SD/PD arms
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not planned as per study plan.
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    3
    2
    1
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Kaplan Meier Estimate of Duration of Best Response

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    End point title
    Kaplan Meier Estimate of Duration of Best Response
    End point description
    Duration of hematologic response and/or improvement was defined as the time from the date response or improvement was first observed to the date of documented relapse or disease progression as defined by the modified IWG 2006 criteria. Particpants who maintained hematologic response and/or improvement through the end of the treatment period were censored as the date of treatment discontinuation or death, whichever occurred first.
    End point type
    Secondary
    End point timeframe
    Response was assessed every 2 cycles following treatment during the first 6 cycles, then every 3 cycles thereafter; median duration of treatment = 5.26 and 3.81 months for SD/PD for oral AZA arms respectively, and 1.84 months for AZA and Durva SD/PD arms
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    6
    5
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Progression Free Survival (PFS)

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    End point title
    Kaplan-Meier Estimate of Progression Free Survival (PFS)
    End point description
    Progression-free survival is defined as the time from first dose to the first documented progressive disease (PD), relapse, or death due to any cause during or after the treatment period, whichever occurred first, according to IWG 2006 response criteria for MDS. Participants who were still alive and progression-free were censored at the date of their last response assessment. Progressive disease is defined as follows: - an increase in BM blasts relative to nadir: •If nadir less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts •If nadir 5% - 10% blasts: ≥ 50% increase in blasts to > 10% blasts •If nadir 10% - 20% blasts: ≥ 50% increase in blasts to > 20% blasts •If nadir 20% - 30% blasts: ≥ 50% increase in blasts to > 30% blasts And any of the following: •At least 50% decrement from maximum remission/response levels in granulocytes or platelets •Reduction in Hgb concentration by ≥ 2 g/dL •Transfusion dependence
    End point type
    Secondary
    End point timeframe
    From first dose to the first documented progressive disease (PD), relapse, or death due to any cause (Up to 91 months)
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    6
    5
    Units: Months
        median (confidence interval 95%)
    14.86 (9.27 to 24.99)
    6.28 (4.50 to 15.19)
    14.70 (1.58 to 99999)
    12.10 (2.17 to 99999)
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Onset to Achieve Stable Disease

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    End point title
    Kaplan-Meier Estimate of Onset to Achieve Stable Disease [3]
    End point description
    A participant was considered as having a stable disease if the disease neither responded nor progressed during or after study treatment.
    End point type
    Secondary
    End point timeframe
    Response was assessed every 2 cycles following treatment during the first 6 cycles, then every 3 cycles thereafter; median duration of treatment = 5.26 and 3.81 months for SD/PD for oral AZA arms respectively, and 1.84 months for AZA and Durva SD/PD arms
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not planned as per study plan.
    End point values
    Progressive Disease (PD) Cohort: Oral Azacitidine Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    22
    5
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Progressive Disease at Baseline who Achieved Stable Disease

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    End point title
    Percentage of Participants with Progressive Disease at Baseline who Achieved Stable Disease [4]
    End point description
    A participant was considered as having a stable disease if the disease neither responded nor progressed during or after study treatment.
    End point type
    Secondary
    End point timeframe
    Response was assessed every 2 cycles following treatment during the first 6 cycles, then every 3 cycles thereafter; median duration of treatment = 5.26 and 3.81 months for SD/PD for oral AZA arms respectively, and 1.84 months for AZA and Durva SD/PD arms
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not planned as per study plan.
    End point values
    Progressive Disease (PD) Cohort: Oral Azacitidine Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    22
    5
    Units: Percentage of Participants
        number (not applicable)
    36.4
    20.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Progressed to Acute Myelogenous Leukemia (AML)

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    End point title
    Percentage of Participants who Progressed to Acute Myelogenous Leukemia (AML)
    End point description
    For all participants who received at least one dose of study drug, continuous monitoring for progression to AML occurred in the post treatment follow up period.
    End point type
    Secondary
    End point timeframe
    From first dose and until death, loss to follow-up, withdrawal of consent for further data collection, or study closure (Up to 91 months)
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    6
    5
    Units: Percentage of Participants
        number (not applicable)
    31.3
    18.2
    33.3
    60.0
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Duration of Stable Disease

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    End point title
    Kaplan-Meier Estimate of Duration of Stable Disease [5]
    End point description
    The duration of stable disease was defined as the time between any two observations of objective disease progression (modified IWG criteria), starting from the first day of dosing with IP. Participants who maintained stable disease through the end of the treatment period were censored at the date of study termination.
    End point type
    Secondary
    End point timeframe
    Response was assessed every 2 cycles following treatment during the first 6 cycles, then every 3 cycles thereafter; median duration of treatment = 5.26 and 3.81 months for SD/PD for oral AZA arms respectively, and 1.84 months for AZA and Durva SD/PD arms
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not planned as per study plan.
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    5
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Time to Progression to AML

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    End point title
    Kaplan-Meier Estimate of Time to Progression to AML
    End point description
    Time to AML progression was defined as the time from the date of first dose of IP until the date the participant had documented progression to AML.
    End point type
    Secondary
    End point timeframe
    From first dose and until death, loss to follow-up, withdrawal of consent for further data collection, or study closure (Up to 91 months)
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    6
    5
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    21.47 (1.68 to 99999)
    6.21 (1.64 to 99999)
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAEs)

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    End point title
    Number of Participants with Treatment Emergent Adverse Events (TEAEs)
    End point description
    TEAEs were defined as AEs occurring or worsening on or after the date of the first dose of oral aza or durva and within 28 days after last dose of oral aza or 90 days after last dose of durva A serious adverse event (SAE) is any: • Death; • Life-threatening event; • Any inpatient hospitalization or prolongation of existing hospitalization; • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect; • Any other important medical event The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.
    End point type
    Secondary
    End point timeframe
    From first dose, until 28 days after the last dose of CC-486 (90 days after the last dose of durvalumab) or the last study visit, whichever date is later (Up to 91 months)
    End point values
    Stable Disease (SD) Cohort: Oral Azacitidine Progressive Disease (PD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Number of subjects analysed
    32
    22
    6
    5
    Units: Participants
        ≥ 1 TEAE
    32
    22
    6
    5
        ≥ 1 TEAE Related to (R/T) Oral Azacitidine (AZA)
    28
    20
    6
    4
        ≥ 1 TEAE R/T Durvalumab (Durva)
    0
    0
    5
    4
        ≥ 1 TEAE R/T Oral AZA or Durva
    28
    20
    6
    4
        ≥ 1 Serious TEAE
    25
    15
    4
    5
        ≥ 1 Serious TEAE R/T Oral AZA
    4
    3
    2
    1
        ≥ 1 Serious TEAE R/T Durva
    0
    0
    1
    1
        ≥ 1 Serious TEAE R/T Oral AZA or Durva
    4
    3
    2
    1
        ≥ 1 NCI CTC Grade (GR) 3 or 4 TEAE
    32
    19
    5
    5
        ≥ 1 NCI CTC GR 3 or 4 TEAE R/T Oral AZA
    18
    10
    4
    3
        ≥ 1 NCI CTC GR 3 or 4 TEAE R/T Durva
    0
    0
    2
    2
        ≥ 1 NCI CTC GR 3 or 4 TEAE R/T AZA or Durva
    18
    10
    4
    3
        ≥ 1 TEAE Leading to Death
    4
    4
    2
    0
        ≥ 1 TEAE Leading to Death R/T Oral AZA
    0
    0
    0
    0
        ≥ 1 TEAE Leading to Death R/T Durva
    0
    0
    0
    0
        ≥ 1 TEAE Leading to Death R/T AZA or Durva
    0
    0
    0
    0
        ≥ 1 TEAE Leading to Dose Reduction of AZA
    10
    8
    1
    0
        ≥ 1 TEAE Leading to Reduction of Durva
    0
    0
    0
    0
        ≥ 1 TEAE Leading to Reduction of AZA or Durva
    10
    8
    1
    0
        ≥1 TEAE Leading to Interruption of AZA
    21
    13
    3
    4
        ≥1 TEAE Leading to Interruption of Durva
    0
    0
    2
    0
        ≥1 TEAE Leading to Interruption of AZA or Durva
    21
    13
    3
    4
        ≥ 1 TEAE Leading to Discontinuation (D/C) of AZA
    15
    8
    4
    4
        ≥ 1 TEAE Leading to D/C of Durva
    0
    0
    3
    3
        ≥ 1 TEAE Leading to D/C of AZA or Durva
    15
    8
    4
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAE and Non-SAEs were collected from first dose, until 28 days after the last dose of CC-486 (90 days after the last dose of durvalumab) or the last study visit, whichever date is later. (Up to 91 months)
    Adverse event reporting additional description
    The number at Risk for All-Cause Mortality represents all enrolled participants. The number at risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents safety population that include all enrolled subjects who have received at least 1 dose of IP and had at least 1 post-dose safety assessment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Stable Disease (SD) Cohort: Oral Azacitidine
    Reporting group description
    -

    Reporting group title
    Stable Disease Cohort: Oral Azacitidine and Durvalumab
    Reporting group description
    -

    Reporting group title
    Progressive Disease Cohort: Oral Azacitidine and Durvalumab
    Reporting group description
    -

    Reporting group title
    Progressive Disease (PD) Cohort: Oral Azacitidine
    Reporting group description
    -

    Serious adverse events
    Stable Disease (SD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease (PD) Cohort: Oral Azacitidine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    26 / 32 (81.25%)
    4 / 6 (66.67%)
    5 / 5 (100.00%)
    15 / 22 (68.18%)
         number of deaths (all causes)
    22
    3
    5
    18
         number of deaths resulting from adverse events
    4
    2
    0
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glioma
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transformation to acute myeloid leukaemia
         subjects affected / exposed
    8 / 32 (25.00%)
    1 / 6 (16.67%)
    3 / 5 (60.00%)
    3 / 22 (13.64%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sarcoma
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    2 / 32 (6.25%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pulmonary oedema
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    White blood cell count increased
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 32 (6.25%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperleukocytosis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Haematemesis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Acute febrile neutrophilic dermatosis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyoderma gangrenosum
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fungaemia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis gangrenous
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Neutropenic sepsis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    9 / 32 (28.13%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    2 / 22 (9.09%)
         occurrences causally related to treatment / all
    1 / 10
    0 / 0
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Serratia bacteraemia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Tumour lysis syndrome
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Stable Disease (SD) Cohort: Oral Azacitidine Stable Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease Cohort: Oral Azacitidine and Durvalumab Progressive Disease (PD) Cohort: Oral Azacitidine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    32 / 32 (100.00%)
    6 / 6 (100.00%)
    5 / 5 (100.00%)
    22 / 22 (100.00%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    1
    1
    Hypertension
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Hypotension
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    3 / 5 (60.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    3
    1
    Superficial vein thrombosis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    7 / 32 (21.88%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    3 / 22 (13.64%)
         occurrences all number
    10
    3
    2
    5
    Generalised oedema
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Fatigue
         subjects affected / exposed
    10 / 32 (31.25%)
    2 / 6 (33.33%)
    4 / 5 (80.00%)
    6 / 22 (27.27%)
         occurrences all number
    33
    3
    7
    6
    Chills
         subjects affected / exposed
    1 / 32 (3.13%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Catheter site erythema
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Asthenia
         subjects affected / exposed
    9 / 32 (28.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    4 / 22 (18.18%)
         occurrences all number
    9
    0
    0
    5
    Oedema peripheral
         subjects affected / exposed
    6 / 32 (18.75%)
    1 / 6 (16.67%)
    3 / 5 (60.00%)
    2 / 22 (9.09%)
         occurrences all number
    6
    1
    4
    2
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Reproductive system and breast disorders
    Penile pain
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oedema genital
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    1 / 22 (4.55%)
         occurrences all number
    4
    0
    2
    1
    Dyspnoea exertional
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    4
    0
    0
    1
    Dyspnoea
         subjects affected / exposed
    9 / 32 (28.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    4 / 22 (18.18%)
         occurrences all number
    13
    0
    0
    4
    Cough
         subjects affected / exposed
    7 / 32 (21.88%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    4 / 22 (18.18%)
         occurrences all number
    7
    0
    2
    4
    Hypoxia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nasal congestion
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    1
    0
    0
    2
    Oropharyngeal pain
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    4
    0
    0
    2
    Pleural effusion
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Productive cough
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    3
    0
    0
    2
    Pulmonary hypertension
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Insomnia
         subjects affected / exposed
    6 / 32 (18.75%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
         occurrences all number
    7
    0
    1
    2
    Depression
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    1
    2
    Delirium
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    4 / 22 (18.18%)
         occurrences all number
    2
    0
    5
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    9
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    5
    0
    0
    1
    Cardiac murmur
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Serum ferritin increased
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Urine output decreased
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    10 / 32 (31.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    6 / 22 (27.27%)
         occurrences all number
    11
    0
    0
    6
    White blood cell count increased
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    5 / 32 (15.63%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    7
    0
    0
    0
    Skin wound
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Spinal compression fracture
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Transfusion reaction
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
         occurrences all number
    2
    0
    1
    3
    Contusion
         subjects affected / exposed
    5 / 32 (15.63%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    14
    0
    0
    2
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Atrial fibrillation
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Tricuspid valve disease
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Sinus bradycardia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Sciatica
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Headache
         subjects affected / exposed
    4 / 32 (12.50%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    12
    4
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    6 / 32 (18.75%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    14
    0
    0
    2
    Lethargy
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    0
    1
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    0
    1
    0
    Neutropenia
         subjects affected / exposed
    12 / 32 (37.50%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    6 / 22 (27.27%)
         occurrences all number
    42
    1
    4
    18
    Anaemia
         subjects affected / exposed
    12 / 32 (37.50%)
    1 / 6 (16.67%)
    3 / 5 (60.00%)
    10 / 22 (45.45%)
         occurrences all number
    40
    1
    18
    28
    Splenomegaly
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    8 / 32 (25.00%)
    1 / 6 (16.67%)
    4 / 5 (80.00%)
    6 / 22 (27.27%)
         occurrences all number
    11
    2
    11
    6
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypoacusis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ear pain
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye haemorrhage
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    21 / 32 (65.63%)
    4 / 6 (66.67%)
    2 / 5 (40.00%)
    11 / 22 (50.00%)
         occurrences all number
    41
    4
    2
    26
    Constipation
         subjects affected / exposed
    13 / 32 (40.63%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    9 / 22 (40.91%)
         occurrences all number
    25
    1
    3
    12
    Dry mouth
         subjects affected / exposed
    1 / 32 (3.13%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    12
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    3 / 32 (9.38%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
         occurrences all number
    6
    2
    2
    2
    Abdominal distension
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    4
    0
    0
    1
    Anal erythema
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gingival bleeding
         subjects affected / exposed
    2 / 32 (6.25%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    4
    0
    1
    1
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    2
    Flatulence
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    3
    0
    0
    1
    Dysphagia
         subjects affected / exposed
    2 / 32 (6.25%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Dyspepsia
         subjects affected / exposed
    1 / 32 (3.13%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    3 / 22 (13.64%)
         occurrences all number
    1
    3
    1
    3
    Duodenogastric reflux
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    4 / 32 (12.50%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    3 / 22 (13.64%)
         occurrences all number
    4
    1
    1
    3
    Periodontal disease
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oral mucosa haematoma
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    24 / 32 (75.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    12 / 22 (54.55%)
         occurrences all number
    34
    6
    3
    17
    Mouth haemorrhage
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Vomiting
         subjects affected / exposed
    18 / 32 (56.25%)
    2 / 6 (33.33%)
    3 / 5 (60.00%)
    11 / 22 (50.00%)
         occurrences all number
    25
    3
    5
    25
    Skin and subcutaneous tissue disorders
    Erythema multiforme
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Night sweats
         subjects affected / exposed
    1 / 32 (3.13%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Petechiae
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    10
    0
    0
    0
    Pruritus
         subjects affected / exposed
    5 / 32 (15.63%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    6
    0
    0
    1
    Rash
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Decubitus ulcer
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    1
    Dermatitis bullous
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 32 (3.13%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    3 / 32 (9.38%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    3
    1
    1
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    2
    2
    Pollakiuria
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    0
    1
    Dysuria
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    5
    0
    0
    0
    Renal cyst
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Urinary retention
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    2
    0
    0
    3
    Urinary incontinence
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Renal disorder
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    4 / 32 (12.50%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    7
    0
    2
    1
    Muscle spasms
         subjects affected / exposed
    2 / 32 (6.25%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Joint effusion
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    0
    1
    Back pain
         subjects affected / exposed
    7 / 32 (21.88%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    9
    0
    1
    1
    Arthralgia
         subjects affected / exposed
    5 / 32 (15.63%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    3 / 22 (13.64%)
         occurrences all number
    7
    0
    0
    3
    Polyarthritis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Myalgia
         subjects affected / exposed
    3 / 32 (9.38%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    5
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 32 (6.25%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Folliculitis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    0
    3
    Diverticulitis
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    2
    0
    0
    2
    Urinary tract infection
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    6
    0
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 32 (18.75%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    13
    1
    0
    3
    Staphylococcal infection
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash pustular
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    2 / 22 (9.09%)
         occurrences all number
    3
    0
    3
    2
    Oral herpes
         subjects affected / exposed
    5 / 32 (15.63%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    5
    0
    0
    1
    Oral candidiasis
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    15 / 32 (46.88%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    8 / 22 (36.36%)
         occurrences all number
    23
    1
    2
    8
    Dehydration
         subjects affected / exposed
    2 / 32 (6.25%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    1
    0
    1
    Gout
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    3 / 22 (13.64%)
         occurrences all number
    2
    0
    0
    5
    Hyperglycaemia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    9
    0
    2
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    3
    Hypomagnesaemia
         subjects affected / exposed
    3 / 32 (9.38%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
         occurrences all number
    3
    0
    3
    2
    Hypokalaemia
         subjects affected / exposed
    4 / 32 (12.50%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    0
    8
    0
    Hypocalcaemia
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    2
    0
    0
    2
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    1
    1
    2
    Hyperphosphataemia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Sep 2015
    An additional investigational product (IP), anti-PD-L1 monoclonal antibody, durvalumab (MEDI4736) in combination with CC-486 (combination therapy), was to be evaluated in this study in addition to the evaluation of CC-486 as monotheraphy.
    27 Mar 2017
    Updated objectives, futility analysis, enrollment period, safety profile, and dosing for clarity and extended trial duration.
    28 Dec 2017
    Protocol text was updated to allow the dose escalation of CC-486 after 2 well tolerated cycles (instead of 4 cycles). The safety assessment observed in the Phase 1 safety run-in portion of the trial was based on 2 dosing cycles and most adverse events occurred early in these cycles.
    17 Jun 2019
    A description of the Extension Phase was presented in Appendix J and mentioned throughout the protocol. The overall duration of the study was extended during the Extension Phase

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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