Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

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

    The EU Clinical Trials Register currently displays   43876   clinical trials with a EudraCT protocol, of which   7294   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An Investigator-Initiated Study To Evaluate Ara-C and Idarubicin in Combination with the Selective Inhibitor Of Nuclear Export (SINE) Selinexor (KPT-330) in Patients with Relapsed Or Refractory AML

    Summary
    EudraCT number
    		 2014-000526-37
    Trial protocol
    		 DE  
    Global end of trial date
    31 Jul 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Feb 2022
    First version publication date
    04 Feb 2022
    Other versions
    Summary report(s)
    		 SAIL CSR Synopsis

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SAIL
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02249091
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GSO Global Clinical Research B.V.
    Sponsor organisation address
    Keizersgracht 62-64, Amsterdam, Netherlands, 1015
    Public contact
    Projectmanagement, GSO Global Clinical Research B.V., +49 4044195460, kranich@gsoglobal.com
    Scientific contact
    Projectmanagement, GSO Global Clinical Research B.V., +49 4044195460, kranich@gsoglobal.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
    31 Jul 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Aug 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jul 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the efficacy of Selinexor in combination with standard chemotherapy in patients with relapsed/ refractory AML by determination of rate of complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet
    Protection of trial subjects
    The study was conducted in compliance with Good Clinical Practice (GCP) and the Declaration of Helsinki, and in accordance with applicable local and regulatory requirements. Patients were closely monitored for adverse events (AEs) during treatment and AEs were captured up to 30 days after the last dose of study medication. The majority of side effects of selinexor were known to be related to low grade nausea and reversible anorexia with weight loss. Fatigue was also observed, and this might be related to reduced caloric (and fluid) intake. These adverse effects were reduced or eliminated with prophylactic appetite stimulants (megestrol and olanzapin or mirtazapine) and prophylactic anti-emesis (ondansetron or similar 5-HT3 antagonist). Platelet count reductions, primarily in patients with baseline thrombocytopenia, were observed, but manageable with dose modification, interruption, platelet transfusions, and/or platelet stimulator support. Diverse ocular symptoms, primarily blurred vision, have been reported and ophthalmologic examinations were part of protocol assessments. The protocol gave detailed guidance for interruption and dose reduction of study medication for the most frequently observed adverse effects. As acetaminophen can interfere with the metabilsm of selinexor patients were advised to minimize the use of products containing acetaminophen. Common side effects of induction therapy with Ara-C and idarubicin are bone marrow suppression. Due to low blood counts the risk for infection was increased. Patients were hospitalized as required during induction therapy to closely monitor their safety parameters and received corresponding treatment, if applicable.
    Background therapy
    		 Background chemotherapy consisted of cytarabine (cytosine arabinoside/Ara-C) and idarubicin according to the 7+3 schedule. All enrolled patients were treated with cytarabine at a dose of 100 mg/m² continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m² i.v. (days 1,3,5) every 4 weeks for a maximum of 2 cycles. During the second cycle the idarubicin dose was restricted to 2 administrations on day 1 and 3. If after 1 or 2 induction cycles patients were not eligibe for or did not undergo stem cell transplantation, 3 cycles of consolidation therapy with Selinexor and cytarabine could be applied until relapse or toxicity developped. The dose of cytarabine was 3 g/m² i.v. for 2h every 12 hours at 3 consecutive days for patients with good performance status and younger than 60 years (in total 6 doses). For patients older than 60 years the dose was 1 g/m² i.v. for 2h every 12 hours at 3 consecutive days.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Jul 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 42
    Worldwide total number of subjects
    42
    EEA total number of subjects
    42
    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)
    26
    From 65 to 84 years
    16
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Between September 2014 and June 2016 a total of 43 patients were registered in the clinical trial at 3 sites in Germany. One patient was a screening failure. Of the remaining 42 patients, the first 27 patients were treated in cohort 1 and the other 15 patients were treated in cohort 2.

    Pre-assignment
    Screening details
    		 Patients with cytological or histological diagnosis of AML were recruited from the patient pool of the participating study sites. Patients had to have relapsed/refractory disease, relapse after stem cell transplantation was permitted.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1
    Arm description
    		 Selinexor was administered at a dose of 40 mg/m² twice weekly orally starting on day 2 of a 4-week induction cycle (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 8 doses per induction cycle. Background chemotherapy consisted of cytarabine and idarubicin according to 7+3 schedule. A maximum of 2 induction cycles was given. After the induction cycles patients not undergoing stem cell transplantation and benefitting from Selinexor could receive 3x4 weeks of consolidation therapy or Selinexor maintenance therapy for a maximum of 1 year or until relapse. The Selinexor schedule remained the same as during the induction therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Selinexor
    Investigational medicinal product code
    KPT-330
    Other name
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    40 mg/m² twice weekly orally starting on day 2 of a 4-week induction cycle (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 8 doses per induction cycle for 1 or 2 induction cycles plus 3 4-weeks cycles (if applicable) plus maintenance until relapse or a maximum of 1 year after start of treatment.

    Arm title
    		 Cohort 2
    Arm description
    		 Selinexor was administered at a flat dose of 60 mg twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18) starting on day 2 (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 6 doses per induction cycle. Background chemotherapy consisted of cytarabine and idarubicin according to 7+3 schedule. A maximum of 2 induction cycles was given. After the induction cycles patients not undergoing stem cell transplantation and benefitting from Selinexor could receive 3x4 weeks of consolidation therapy or Selinexor maintenance therapy for a maximum of 1 year or until relapse. The Selinexor schedule remained the same as during the induction therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Selinexor
    Investigational medicinal product code
    KPT-330
    Other name
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    60 mg twice weekly orally starting on day 2 in weeks 1-3 of a 4-week induction cycle (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 6 doses per induction cycle for 1 or 2 induction cycles plus 3 4-weeks cycles (if applicable) plus maintenance until relapse or a maximum of 1 year after start of treatment.

    Number of subjects in period 1
    		Cohort 1 Cohort 2
    Started
    27
    15
    Completed
    7
    2
    Not completed
    20
    13
         Adverse event, serious fatal
    3
    4
         Consent withdrawn by subject
    2
    2
         Physician decision
    4
    1
         CR with subsequent donor lymphocyte infusion
    1
    -
         Adverse event, non-fatal
    1
    -
         Stable disease with following SCT
    -
    1
         Refractory AML
    1
    1
         Ongoing bone marrow aplasia, periph. pancytopenia
    -
    1
         Lack of efficacy
    8
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    		 Selinexor was administered at a dose of 40 mg/m² twice weekly orally starting on day 2 of a 4-week induction cycle (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 8 doses per induction cycle. Background chemotherapy consisted of cytarabine and idarubicin according to 7+3 schedule. A maximum of 2 induction cycles was given. After the induction cycles patients not undergoing stem cell transplantation and benefitting from Selinexor could receive 3x4 weeks of consolidation therapy or Selinexor maintenance therapy for a maximum of 1 year or until relapse. The Selinexor schedule remained the same as during the induction therapy.

    Reporting group title
    Cohort 2
    Reporting group description
    		 Selinexor was administered at a flat dose of 60 mg twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18) starting on day 2 (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 6 doses per induction cycle. Background chemotherapy consisted of cytarabine and idarubicin according to 7+3 schedule. A maximum of 2 induction cycles was given. After the induction cycles patients not undergoing stem cell transplantation and benefitting from Selinexor could receive 3x4 weeks of consolidation therapy or Selinexor maintenance therapy for a maximum of 1 year or until relapse. The Selinexor schedule remained the same as during the induction therapy.

    Reporting group values
    		 Cohort 1 Cohort 2 Total
    Number of subjects
    		 27 15 42
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 58.0 (22 to 78) 60.0 (29 to 77) -
    Gender categorical
    Units: Subjects
        Female
    		 11 6 17
        Male
    		 16 9 25
    Leukemia diagnosis
    Units: Subjects
        De-novo AML
    		 19 12 31
        Secondary AML
    		 6 3 9
        Therapy-induced AML
    		 2 0 2
    Prior stem cell transplantation (SCT)
    Units: Subjects
        Yes
    		 10 7 17
        No
    		 17 8 25
    Duration of remission prior SAIL
    Units: Subjects
        <12 months
    		 9 4 13
        >12 months
    		 11 7 18
        Refractory disease
    		 7 4 11
    Subject analysis sets

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set included all 42 patients who had received at least one dose of study medication and for whom post-baseline efficacy data were available.

    Subject analysis sets values
    		 Full Analysis Set
    Number of subjects
    42
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        median (full range (min-max))
    59.5 (22 to 78)
    Gender categorical
    Units: Subjects
        Female
    17
        Male
    25
    Leukemia diagnosis
    Units: Subjects
        De-novo AML
    31
        Secondary AML
    9
        Therapy-induced AML
    2
    Prior stem cell transplantation (SCT)
    Units: Subjects
        Yes
    17
        No
    25
    Duration of remission prior SAIL
    Units: Subjects
        <12 months
    13
        >12 months
    18
        Refractory disease
    11

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    		 Selinexor was administered at a dose of 40 mg/m² twice weekly orally starting on day 2 of a 4-week induction cycle (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 8 doses per induction cycle. Background chemotherapy consisted of cytarabine and idarubicin according to 7+3 schedule. A maximum of 2 induction cycles was given. After the induction cycles patients not undergoing stem cell transplantation and benefitting from Selinexor could receive 3x4 weeks of consolidation therapy or Selinexor maintenance therapy for a maximum of 1 year or until relapse. The Selinexor schedule remained the same as during the induction therapy.

    Reporting group title
    Cohort 2
    Reporting group description
    		 Selinexor was administered at a flat dose of 60 mg twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18) starting on day 2 (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 6 doses per induction cycle. Background chemotherapy consisted of cytarabine and idarubicin according to 7+3 schedule. A maximum of 2 induction cycles was given. After the induction cycles patients not undergoing stem cell transplantation and benefitting from Selinexor could receive 3x4 weeks of consolidation therapy or Selinexor maintenance therapy for a maximum of 1 year or until relapse. The Selinexor schedule remained the same as during the induction therapy.

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set included all 42 patients who had received at least one dose of study medication and for whom post-baseline efficacy data were available.

    Primary: Number of subjects with CR/CRi = Overall Response Rate

    		 Close Top of page
    End point title
    		 Number of subjects with CR/CRi = Overall Response Rate
    End point description
    Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic CR with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet: CR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease. CRi: Same as CR, but ANC may be <1.0x10^9/L and/or Platelet count <100x10^9/L. Patients with morphologic leukemia-free state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease. The best response after selinexor treatment was analyzed, thus the best response after induction cycle(s).
    End point type
    Primary
    End point timeframe
    1-2 induction cycles (4-8 weeks)
    End point values
    		 Cohort 1 Cohort 2 Full Analysis Set
    Number of subjects analysed
    27
    15
    42
    Units: Number of subjects
        Number of subjects with CR
    6
    3
    9
        Number of subjects with CRi
    9
    2
    11
        Number of subjects with MLFS
    0
    1
    1
        Non-responder
    12
    9
    21
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Cohort 2 v Cohort 1 v Full Analysis Set
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0023
    Method
    		 Fisher exact
    Parameter type
    		 Wilson
    Point estimate
    50
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 37.7
         upper limit
    		 62.3

    Secondary: Number of subjects with partial remission (PR) = Rate of PR

    		 Close Top of page
    End point title
    		 Number of subjects with partial remission (PR) = Rate of PR
    End point description
    Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of partial remission (PR), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet: PR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count > 100x10^9/L, at least a 50% decrease in the percentage of bone marrow aspirate blasts to 5-25%, or bone marrow blasts <5% with persistent Auer rods. The best response after selinexor treatment was analyzed, thus the best response after the induction cycle(s).
    End point type
    Secondary
    End point timeframe
    1-2 induction cycles (4-8 weeks)
    End point values
    		 Cohort 1 Cohort 2 Full Analysis Set
    Number of subjects analysed
    27
    15
    42
    Units: subjects
        Number of subjects with PR
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects transplanted after induction therapy (Stem Cell Transplantation)

    		 Close Top of page
    End point title
    		 Number of subjects transplanted after induction therapy (Stem Cell Transplantation)
    End point description
    End point type
    Secondary
    End point timeframe
    1-2 induction cycles (4-8 weeks)
    End point values
    		 Cohort 1 Cohort 2 Full Analysis Set
    Number of subjects analysed
    27
    15
    42
    Units: subjects
        SCT applied
    11
    4
    15
        SCT not applied
    16
    11
    27
    No statistical analyses for this end point

    Secondary: Early death rate

    		 Close Top of page
    End point title
    		 Early death rate
    End point description
    Early death was defined as death before the end of the first induction cycle.
    End point type
    Secondary
    End point timeframe
    One induction cycle (4 weeks)
    End point values
    		 Cohort 1 Cohort 2 Full Analysis Set
    Number of subjects analysed
    27
    15
    42
    Units: subjects
        Number of subjects with early death
    0
    4
    4
    No statistical analyses for this end point

    Secondary: Event-Free Survival

    		 Close Top of page
    End point title
    		 Event-Free Survival
    End point description
    Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.
    End point type
    Secondary
    End point timeframe
    Time from registration to event, max. 2 years.
    End point values
    		 Cohort 1 Cohort 2 Full Analysis Set
    Number of subjects analysed
    27
    15
    42
    Units: months
    median (confidence interval 95%)
        Event-free survival
    5.6 (2.9 to 12.6)
    4.3 (0.9 to 10.4)
    4.9 (3.0 to 8.0)
    No statistical analyses for this end point

    Secondary: Progression-free survival

    		 Close Top of page
    End point title
    		 Progression-free survival
    End point description
    Progression-free survival (PFS) was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Subjects were censored at the date of the last follow-up visit if they were alive without relapse. Disease progression was defined as presence of >50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%.
    End point type
    Secondary
    End point timeframe
    Time from registration to event, max. 2 years.
    End point values
    		 Cohort 1 Cohort 2 Full Analysis Set
    Number of subjects analysed
    27
    15
    42
    Units: months
    median (confidence interval 95%)
        Progression-free survival
    6.3 (2.3 to 26.3)
    4.3 (0.9 to 12.9)
    6.1 (2.3 to 12.9)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Throughout the treatment period from start of treatment until one month after the last dose of study medication, on average 2 months.
    Adverse event reporting additional description
    AEs could be spontaneously reported or elicited during open-ended questioning, examination, or evaluation of a subject. In order to prevent reporting bias, investigators were advised not to question subjects regarding specific occurrence of one or more AEs. AEs were requested to be captured at each patient visit.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 NCI-CTCAE
    Dictionary version
    4.03
    Reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    		 Selinexor was administered at a dose of 40 mg/m² twice weekly orally starting on day 2 of a 4-week induction cycle (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 8 doses per induction cycle. Background chemotherapy consisted of cytarabine and idarubicine according to 7+3 schedule. A maximum of 2 induction cycles was given. After the induction cycles patients not undergoing stem cell transplantation and benefitting from Selinexor could receive 3x4 weeks of consolidation therapy or Selinexor maintenance therapy for a maximum of 1 year or until relapse. The Selinexor schedule remained the same as during the induction therapy.

    Reporting group title
    Cohort 2
    Reporting group description
    		 Selinexor was administered at a flat dose of 60 mg twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18) starting on day 2 (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) with a total of 6 doses per induction cycle. Background chemotherapy consisted of cytarabine and idarubicine according to 7+3 schedule. A maximum of 2 induction cycles was given. After the induction cycles patients not undergoing stem cell transplantation and benefitting from Selinexor could receive 3x4 weeks of consolidation therapy or Selinexor maintenance therapy for a maximum of 1 year or until relapse. The Selinexor schedule remained the same as during the induction therapy.

    Serious adverse events
    		 Cohort 1 Cohort 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 27 (44.44%)
    8 / 15 (53.33%)
         number of deaths (all causes)
    16
    9
         number of deaths resulting from adverse events
    7
    6
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
    Additional description: Neutropenia
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fracture
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Asystole
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Stroke
    Additional description: Multiple brain infarctions
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Subarachnoidal hemorrhage
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow hypocellular
    Additional description: Bone marrow aplasia
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 15 (13.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fever
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General weakness
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SIRS
    Additional description: Systemic inflammatory response syndrom
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Immune system disorders
    GvHD
    Additional description: Graft-versus-host-disease
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemophagocytosis syndrome
    Additional description: Lymphohistiocytic syndrome; cause of patient's death according to autopsy report: hemophagocytosis syndrome with acute cardiac decompensation
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Septic shock
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
    Additional description: Pneumonia
         subjects affected / exposed
    3 / 27 (11.11%)
    2 / 15 (13.33%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Sepsis
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1 Cohort 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 27 (100.00%)
    15 / 15 (100.00%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    5 / 27 (18.52%)
    2 / 15 (13.33%)
         occurrences all number
    7
    3
    Hypertension
         subjects affected / exposed
    2 / 27 (7.41%)
    3 / 15 (20.00%)
         occurrences all number
    2
    3
    Hypotension
         subjects affected / exposed
    12 / 27 (44.44%)
    7 / 15 (46.67%)
         occurrences all number
    16
    7
    General disorders and administration site conditions
    Injection site reaction
         subjects affected / exposed
    10 / 27 (37.04%)
    3 / 15 (20.00%)
         occurrences all number
    12
    5
    Edema face
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 15 (0.00%)
         occurrences all number
    3
    0
    Edema limbs
         subjects affected / exposed
    6 / 27 (22.22%)
    5 / 15 (33.33%)
         occurrences all number
    8
    6
    Fatigue
         subjects affected / exposed
    18 / 27 (66.67%)
    9 / 15 (60.00%)
         occurrences all number
    23
    15
    Fever
         subjects affected / exposed
    2 / 27 (7.41%)
    5 / 15 (33.33%)
         occurrences all number
    2
    9
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    2 / 27 (7.41%)
    2 / 15 (13.33%)
         occurrences all number
    3
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 27 (3.70%)
    2 / 15 (13.33%)
         occurrences all number
    1
    2
    Dyspnoea
         subjects affected / exposed
    5 / 27 (18.52%)
    2 / 15 (13.33%)
         occurrences all number
    5
    2
    Epistaxis
         subjects affected / exposed
    10 / 27 (37.04%)
    8 / 15 (53.33%)
         occurrences all number
    13
    13
    Pleural effusion
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 15 (6.67%)
         occurrences all number
    3
    1
    Psychiatric disorders
    Depression
         subjects affected / exposed
    5 / 27 (18.52%)
    3 / 15 (20.00%)
         occurrences all number
    5
    3
    Insomnia
         subjects affected / exposed
    5 / 27 (18.52%)
    2 / 15 (13.33%)
         occurrences all number
    6
    2
    Investigations
    Creatinine increased
         subjects affected / exposed
    3 / 27 (11.11%)
    2 / 15 (13.33%)
         occurrences all number
    3
    2
    Neutrophil count decreased
         subjects affected / exposed
    12 / 27 (44.44%)
    6 / 15 (40.00%)
         occurrences all number
    14
    15
    Platelet count decreased
         subjects affected / exposed
    19 / 27 (70.37%)
    7 / 15 (46.67%)
         occurrences all number
    33
    23
    Weight gain
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    White blood cell decreased
         subjects affected / exposed
    17 / 27 (62.96%)
    9 / 15 (60.00%)
         occurrences all number
    21
    23
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    4 / 27 (14.81%)
    1 / 15 (6.67%)
         occurrences all number
    6
    1
    Cardiac disorders
    Left ventricular systolic dysfunction
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    Sinus tachycardia
         subjects affected / exposed
    3 / 27 (11.11%)
    3 / 15 (20.00%)
         occurrences all number
    3
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    9 / 27 (33.33%)
    6 / 15 (40.00%)
         occurrences all number
    12
    6
    Dysgeusia
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 15 (0.00%)
         occurrences all number
    3
    0
    Headache
         subjects affected / exposed
    5 / 27 (18.52%)
    3 / 15 (20.00%)
         occurrences all number
    10
    4
    Presyncope
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    Syncope
         subjects affected / exposed
    5 / 27 (18.52%)
    1 / 15 (6.67%)
         occurrences all number
    5
    1
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    20 / 27 (74.07%)
    5 / 15 (33.33%)
         occurrences all number
    33
    27
    Febrile neutropenia
         subjects affected / exposed
    23 / 27 (85.19%)
    5 / 15 (33.33%)
         occurrences all number
    30
    27
    Ear and labyrinth disorders
    Hearing impaired
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 15 (6.67%)
         occurrences all number
    4
    1
    Vertigo
         subjects affected / exposed
    4 / 27 (14.81%)
    0 / 15 (0.00%)
         occurrences all number
    4
    0
    Eye disorders
    Blurred vision
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 15 (0.00%)
         occurrences all number
    3
    0
    Dry eye
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    10 / 27 (37.04%)
    1 / 15 (6.67%)
         occurrences all number
    10
    1
    Colitis
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 15 (0.00%)
         occurrences all number
    3
    0
    Constipation
         subjects affected / exposed
    7 / 27 (25.93%)
    7 / 15 (46.67%)
         occurrences all number
    8
    10
    Diarrhoea
         subjects affected / exposed
    24 / 27 (88.89%)
    11 / 15 (73.33%)
         occurrences all number
    99
    32
    Dysphagia
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    Mucositis oral
         subjects affected / exposed
    12 / 27 (44.44%)
    6 / 15 (40.00%)
         occurrences all number
    19
    7
    Nausea
         subjects affected / exposed
    23 / 27 (85.19%)
    13 / 15 (86.67%)
         occurrences all number
    49
    19
    Oral haemorrhage
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 15 (0.00%)
         occurrences all number
    4
    0
    Stomach pain
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 15 (6.67%)
         occurrences all number
    3
    1
    Toothache
         subjects affected / exposed
    4 / 27 (14.81%)
    0 / 15 (0.00%)
         occurrences all number
    5
    0
    Vomiting
         subjects affected / exposed
    22 / 27 (81.48%)
    9 / 15 (60.00%)
         occurrences all number
    46
    13
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    Rash maculo-papular
         subjects affected / exposed
    4 / 27 (14.81%)
    1 / 15 (6.67%)
         occurrences all number
    6
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 27 (3.70%)
    3 / 15 (20.00%)
         occurrences all number
    1
    3
    Urinary incontinence
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    2
    Chest wall pain
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    Pain in extremity
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 15 (6.67%)
         occurrences all number
    3
    1
    Infections and infestations
    Catheter related infection
         subjects affected / exposed
    4 / 27 (14.81%)
    1 / 15 (6.67%)
         occurrences all number
    4
    1
    Lung infection
         subjects affected / exposed
    8 / 27 (29.63%)
    4 / 15 (26.67%)
         occurrences all number
    13
    15
    Sepsis
         subjects affected / exposed
    7 / 27 (25.93%)
    3 / 15 (20.00%)
         occurrences all number
    7
    4
    Sinusitis
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 15 (0.00%)
         occurrences all number
    4
    0
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    22 / 27 (81.48%)
    8 / 15 (53.33%)
         occurrences all number
    40
    10
    Hyperglycaemia
         subjects affected / exposed
    4 / 27 (14.81%)
    1 / 15 (6.67%)
         occurrences all number
    4
    2
    Hypocalcaemia
         subjects affected / exposed
    4 / 27 (14.81%)
    1 / 15 (6.67%)
         occurrences all number
    5
    1
    Hypokalaemia
         subjects affected / exposed
    17 / 27 (62.96%)
    2 / 15 (13.33%)
         occurrences all number
    27
    2
    Hypomagnesaemia
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 15 (6.67%)
         occurrences all number
    3
    1
    Hyponatraemia
         subjects affected / exposed
    3 / 27 (11.11%)
    4 / 15 (26.67%)
         occurrences all number
    4
    6
    Hypophosphataemia
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 15 (0.00%)
         occurrences all number
    4
    0
    Weight loss
         subjects affected / exposed
    2 / 27 (7.41%)
    2 / 15 (13.33%)
         occurrences all number
    3
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Sep 2014
    Protocol v1.2 dd. Sep01, 2014: The full ophthalmologic examination at baseline and if clinically indicated during treatment has been implemented into the protocol as part of the safety assessments in order to help determine if selinexor is contributing any visual changes. In phase I clinical trials, a baseline full ophthalmologic examination had been implemented since November 2012, because there had been few reports of "blurred vision" and other visual changes during 2 phase I trials with selinexor.
    24 Aug 2015
    Protocol v2.0 dated Aug24, 2015: The findings of the study showed that very good response was achieved with treatment with Ara-C and idarubicin in combination with selinexor. The most frequent non-haematologic AEs observed had included vomiting, diarrhoea, nausea, fatigue, anorexia and neutropenic fever. Taking into account the promising results, 15 more subjects were planned to be recruited reaching a total of approximately 40 subjects for the trial. The sample size calculation, statistical considerations, the anticipated enrolment period, and the planned duration of the study had been updated accordingly. The new cohort of subjects was to receive selinexor at a flat dose of 60 mg twice weekly in weeks 1-3 of a 4-week cycle. The objective of the new dose regimen was to improve management of most common AEs and further investigate the response to treatment. Dose modification levels had been adapted accordingly. Furthermore, several sections in the protocol related to treatment, dose modification, concomitant medication, and supportive care guidelines were updated according to the updated Investigator's Brochure v5.0 dated Aug12, 2015.
    13 Jan 2017
    Protocol v3.1 dated Jan13, 2017: The protocol was updated following the regular update of the Reference Safety Information (Investigator's Brochure Selinexor). Also finishing Source Data Verification and collecting data for final study results revealed the necessity of additional data to interpret the safety and efficacy. Additional data (time to platelet recovery to platelets >=50x10^9/L and >=100x10^9/L and time to Absolute neutrophil count (ANC) recovery to ANC >=0.5x10^9/L and >=1.0x10^9/L) were to be collected to define the recovery times for platelets and neutrophils in more detail. The primary objective "remission status after induction" was to be classified according to Doehner et al.: the recommendations from the European LeukemiaNet (Blood. 2004 Jan 15;103(2):479-85), and not according to Cheson et al. An Independent Data Monitoring Committee consisting of 2-3 AML specialists was implemented to make recommendations regarding the interpretation of the safety and efficacy results. The protocol was updated accordingly to the Investigator's Brochure (IB) v6.0 dated Nov14, 2016. Subsequently to the IB update, all cases of cerebellar toxicity >= Grade 3 were added as Adverse Events of Special Interest and were to be reported in the same format and timeframe as Serious Adverse Events. An addendum to subject's information (v3.0 dated Dec14, 2016) for subjects still in maintenance therapy and follow-up had been updated in accordance with the amended protocol and IB.

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

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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/32515072
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 10 08:42:04 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA