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    Clinical Trial Results:
    WT1 Immunity via DNA fusion Gene Vaccination in Haematological Malignancies by intramuscular injection followed by intramuscular electroporation.

    Summary
    EudraCT number
    		 2009-017340-14
    Trial protocol
    		 GB  
    Global end of trial date
    04 Jun 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Dec 2021
    First version publication date
    13 Dec 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    RHMCAN0700
    Additional study identifiers
    ISRCTN number
    		 ISRCTN62678383
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 ISRCTN reference number : ISRCTN62678383, Gene Therapy Advisory Committee reference number: 173
    Sponsors
    Sponsor organisation name
    University Hospital Southampton NHS Foundation Trust
    Sponsor organisation address
    Southampton General Hospital, Level E, Laboratory & Pathology Block, SCBR, MP 138, Southampton, United Kingdom, SO16 6YD
    Public contact
    University of Southampton Clinical Trials Unit, University of Southampton Clinical Trials Unit, 0044 2381205154, ctu@soton.ac.uk
    Scientific contact
    University of Southampton Clinical Trials Unit, University of Southampton Clinical Trials Unit, 0044 2381205154, ctu@soton.ac.uk
    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
    21 Jan 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jun 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The principal research questions are: a) In patients with chronic myeloid leukemia (CML) whether WT1 DNA vaccination can reduce the measurable amount of the leukaemia-derived marker (BCR-ABL and WT-1transcripts), of which BCR-ABL is already used for clinical monitoring of disease response and decision making. b) In patients with acute myeloid leukemia (AML) to examine the effect of WT1 DNA vaccination on time to disease progression in a patient group that has a 70% risk of disease recurrence in 2 years.
    Protection of trial subjects
    Painkillers (eg. paracetamol) were provided if needed. Of note, this was not necessary for any patient in the study GTAC 089. At all visits the physical examination included a careful examination of the injection site including measurements of the circumference of the extremity where appropriate if there was clinical evidence of a local reaction. Patients were monitored throughout the study period for anti-DNA antibodies, rheumatoid factors and evidence of muscle destruction. Levels of anti-DNA antibodies and rheumatoid factors were measured according to standard local ranges. If these tests became significantly positive, after previously being absent or normal or other clinically significant signs of autoimmunity appear, vaccination would have been terminated and rheumatology consultation sought. For all patients pain or discomfort and level of distress was assessed 1 hr after injection (or after recovery from sedation) and at 48 hrs. The information was collected using questionnaires. Vital signs were monitored closely after administration of the DNA. If anaphylaxis occurs, the patient were treated immediately, initially with adrenaline, hydrocortisone and chlorpheniramine. If CTC toxicity grade>2 occurs in a particular patient, vaccination were to be paused. Further vaccination may have been offered after normalization if appropriate in the opinion of the treating clinician and only after documented discussion with the UoSCTU and lead investigators.
    Background therapy
    		 Steroids or other drugs with a likely effect on immune competence are not permitted during the course of the trial. Concomitant medication may be given as medically indicated. Patients with CML-CP will continue on tyrosine kinase inhibitor therapy.
    Evidence for comparator
    		 Patients with HLA A2-ve genotype were not vaccinated and formed the control group.
    Actual start date of recruitment
    01 Feb 2011
    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
    United Kingdom: 23
    Worldwide total number of subjects
    23
    EEA total number of subjects
    23
    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)
    18
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Between 1st February 2011 and 26th February 2013, 23 CML patients were registered from three UK hospitals (Southampton General Hospital, Hammersmith Hospital and Royal Devon and Exeter Hospital). The CML arm of the trial was terminated early by the funders due to poor recruitment and therefore the AML arm were not opened to recruitment.

    Pre-assignment
    Screening details
    		 Screening details given in the pre-assignment period

    Pre-assignment period milestones
    Number of subjects started
    		 91 [1]
    Number of subjects completed
    		 22

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Not eligible: 47
    Reason: Number of subjects
    		 Patient choice: 7
    Reason: Number of subjects
    		 Other: 2
    Reason: Number of subjects
    		 Unknown: 12
    Reason: Number of subjects
    		 Physician decision: 1
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Pre-assignment period includes all patients assessed for eligibility and is therefore greater than the number actually enrolled.
    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 HLA A2 positive
    Arm description
    		 Intervention group: all eligible, consenting CML patients who were HLA A2 positive
    Arm type
    		 Experimental

    Investigational medicinal product name
    p.DOM-WT1-37
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    p.DOM-WT1-37: 1mg/dose/vaccine The DNA vaccine was administered 6 times every 4 weeks followed by a further 6 vaccinations every 3 months to maximum of 24 months.

    Investigational medicinal product name
    p.DOM-WT1-126
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    p.DOM-WT1-126: 1mg/dose/vaccine The DNA vaccine will be administered 6 times every 4 weeks followed by a further 6 vaccinations every 3 months to maximum of 24 months.

    Arm title
    		 HLA A2 Negative
    Arm description
    		 Control group: all eligible and consenting patients who were HLA A2 negative
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1 [2]
    		HLA A2 positive HLA A2 Negative
    Started
    13
    9
    Completed
    4
    2
    Not completed
    9
    7
         Physician decision
    1
    -
         Consent withdrawn by subject
    6
    5
         Imatinib dose decreased
    2
    -
         Changed to dasatinib
    -
    1
         Other medical urgent issues
    -
    1
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: One patient was enrolled but excluded before baseline period and HLA A2 status obtained due to achieving CMR

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    HLA A2 positive
    Reporting group description
    		 Intervention group: all eligible, consenting CML patients who were HLA A2 positive

    Reporting group title
    HLA A2 Negative
    Reporting group description
    		 Control group: all eligible and consenting patients who were HLA A2 negative

    Reporting group values
    		 HLA A2 positive HLA A2 Negative Total
    Number of subjects
    		 13 9 22
    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))
    		 52 (23 to 66) 56 (42 to 73) -
    Gender categorical
    Units: Subjects
        Female
    		 7 4 11
        Male
    		 6 4 10
        Not recorded
    		 0 1 1
    BCR-ABL Transcript type
    Units: Subjects
        e13/e14a2
    		 0 1 1
        e13a2
    		 2 3 5
        e13a2/e14a2
    		 0 1 1
        e14a2
    		 7 2 9
        unknown
    		 3 1 4
        Not analysed
    		 1 1 2
    BCR_ABL Result
    Units: Subjects
        Positive
    		 12 8 20
        Undetectable
    		 0 0 0
        Failed
    		 0 0 0
        Not analysed
    		 1 1 2
    WT1 result
    Units: Subjects
        Positive
    		 12 7 19
        Undetectable
    		 0 1 1
        Failed
    		 0 0 0
        Not analysed
    		 1 1 2
    Subject analysis sets

    Subject analysis set title
    ITT population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All registered patients who obtained an HLA A2 status following the intention-to-treat principle.

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    For safety analyses, all patients with positive HLA A2 status who received at least one trial drug administration were evaluable for toxicity. All controls (HLA A2 negative) were included in the safety analyses, where relevant.

    Subject analysis set title
    Molecular analysis set
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The analyses on molecular response were performed on all patients with molecular data at a minimum of 2 post-baseline time points (HLA A2 positive patients must also have received at least 1 dose of the vaccine).

    Subject analysis sets values
    		 ITT population Safety analysis set Molecular analysis set
    Number of subjects
    22
    21
    20
    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))
    53 (23 to 73)
    52 (23 to 73)
    53 (23 to 73)
    Gender categorical
    Units: Subjects
        Female
    11
    10
    10
        Male
    10
    10
    10
        Not recorded
    1
    1
    0
    BCR-ABL Transcript type
    Units: Subjects
        e13/e14a2
    1
    1
    1
        e13a2
    5
    5
    5
        e13a2/e14a2
    1
    1
    1
        e14a2
    9
    9
    9
        unknown
    4
    5
    4
        Not analysed
    2
    1
    0
    BCR_ABL Result
    Units: Subjects
        Positive
    20
    20
    20
        Undetectable
    0
    0
    0
        Failed
    0
    0
    0
        Not analysed
    2
    1
    0
    WT1 result
    Units: Subjects
        Positive
    19
    19
    19
        Undetectable
    1
    1
    1
        Failed
    0
    0
    0
        Not analysed
    2
    1
    0

    End points

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    End points reporting groups
    Reporting group title
    HLA A2 positive
    Reporting group description
    		 Intervention group: all eligible, consenting CML patients who were HLA A2 positive

    Reporting group title
    HLA A2 Negative
    Reporting group description
    		 Control group: all eligible and consenting patients who were HLA A2 negative

    Subject analysis set title
    ITT population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All registered patients who obtained an HLA A2 status following the intention-to-treat principle.

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    For safety analyses, all patients with positive HLA A2 status who received at least one trial drug administration were evaluable for toxicity. All controls (HLA A2 negative) were included in the safety analyses, where relevant.

    Subject analysis set title
    Molecular analysis set
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The analyses on molecular response were performed on all patients with molecular data at a minimum of 2 post-baseline time points (HLA A2 positive patients must also have received at least 1 dose of the vaccine).

    Primary: Molecular response of BCR-ABL (major or minor response or CMR)

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    End point title
    		 Molecular response of BCR-ABL (major or minor response or CMR)
    End point description
    1) For patients with a baseline BCR-ABL transcript level less than 11: CMR: 0 BCR-ABL transcript level with ABL control copy greater than or equal to 32,000; in TWO CONSECUTIVE tests. These patients cannot be assessed for a major or minor response as defined below. 2) For patients with a baseline BCR-ABL transcript level greater than or equal to 11: a. CMR: 0 BCR-ABL transcript level with ABL control copy greater than or equal to 32,000; in TWO CONSECUTIVE tests. b. Major response: a fall greater than 1 log in the BCR-ABL transcript level ratio.* c. Minor response: a fall greater than 0.5 log in the BCR-ABL transcript level ratio.* *Confirmed in an ABL control copy greater than or equal to 32,000 in two consecutive samples at any time during follow up.
    End point type
    Primary
    End point timeframe
    Molecular samples collected during various follow up visits and compared to the baseline sample. Only responses measured at weeks 4, 8, 12, 16, 20, 32 and 11, 17 and 23 months were considered in the analysis as pre-defined in the protocol.
    End point values
    		 HLA A2 positive HLA A2 Negative Molecular analysis set
    Number of subjects analysed
    12 [1]
    8 [2]
    20
    Units: Number
        BCR-ABL response (CMR or minor or major)
    1
    1
    2
        BCR-ABL no response (CMR or minor or major)
    11
    7
    18
    Notes
    [1] - Number in molecular analysis population
    [2] - Number in molecular analysis population
    Statistical analysis title
    		 Fisher's exact test
    Statistical analysis description
    Fisher’s exact test was used to compare differences in proportions of molecular response in CML patients versus controls.
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.999
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Molecular response of BCR-ABL response (major or CMR)

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    End point title
    		 Molecular response of BCR-ABL response (major or CMR)
    End point description
    1) For patients with a baseline BCR-ABL transcript level less than 11: CMR: 0 BCR-ABL transcript level with ABL control copy greater than or equal to 32,000; in TWO CONSECUTIVE tests. These patients cannot be assessed for a major or minor response as defined below. 2) For patients with a baseline BCR-ABL transcript level greater than or equal to 11: a. CMR: 0 BCR-ABL transcript level with ABL control copy greater than or equal to 32,000; in TWO CONSECUTIVE tests. b. Major response: a fall greater than 1 log in the BCR-ABL transcript level ratio.* *Confirmed in an ABL control copy greater than or equal to 32,000 in two consecutive samples at any time during follow up.
    End point type
    Secondary
    End point timeframe
    Molecular samples collected during various follow up visits and compared to the baseline sample. Only responses measured at weeks 4, 8, 12, 16, 20, 32 and 11, 17 and 23 months were considered in the analysis as pre-defined in the protocol.
    End point values
    		 HLA A2 positive HLA A2 Negative Molecular analysis set
    Number of subjects analysed
    12 [3]
    8 [4]
    20
    Units: Number
        BCR-ABL response (CMR or major)
    1
    1
    2
        BCR-ABL no response (CMR or major)
    11
    7
    18
    Notes
    [3] - Number in molecular analysis population
    [4] - Number in molecular analysis population
    Statistical analysis title
    		 Fisher's exact test
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 > 0.999
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [5] - Fisher’s exact test was used to compare differences in proportions of molecular response in CML patients versus controls.

    Secondary: Molecular response of WT1 (CMR or minor or major)

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    End point title
    		 Molecular response of WT1 (CMR or minor or major)
    End point description
    1) For patients with a baseline WT1/GUS ratio less than 0.1%: a) CMR: 0% WT1/GUS ratio with GUS control copy greater than or equal to 32,000; in TWO CONSECUTIVE tests. b) These patients cannot be assessed for a major or minor response as defined below. 2) For patients with a baseline WT1/GUS ratio greater than or equal to 0.1%: a) CMR: 0% WT1/GUS ratio with GUS control copy greater than or equal to 32,000; in TWO CONSECUTIVE tests. b) Major response: a fall greater than 1 log in the WT1/GUS ratio.* c) Minor response: a fall greater than 0.5 log in the WT1/GUS ratio.* *Confirmed in a GUS control copy greater than or equal to 32,000 in two consecutive samples at any time during follow up.
    End point type
    Secondary
    End point timeframe
    Molecular samples collected during various follow up visits and compared to the baseline sample. Only responses measured at weeks 4, 8, 12, 16, 20, 32 and 11, 17 and 23 months were considered in the analysis as pre-defined in the protocol.
    End point values
    		 HLA A2 positive HLA A2 Negative Molecular analysis set
    Number of subjects analysed
    12 [6]
    8 [7]
    20
    Units: Number
        WT1 response (CMR or minor or major)
    2
    1
    3
        WT1 no response (CMR or minor or major)
    10
    7
    17
    Notes
    [6] - Number in molecular analysis set
    [7] - Number in molecular analysis population
    Statistical analysis title
    		 Fisher's exact test
    Comparison groups
    HLA A2 Negative v HLA A2 positive v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 > 0.999
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [8] - Fisher’s exact test was used to compare differences in proportions of molecular response in CML patients versus controls.

    Secondary: Time to disease progression

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    End point title
    		 Time to disease progression
    End point description
    Disease progression for CML patients is defined as a loss in complete haematological response, where at least one factor falls out of the following ranges 56: o WBC < 10 x 109/L o Basophils < 5% o No myelocytes, promyelocytes, myeloblasts in the differential o Platelet count < 450 x 109/L o Spleen nonpalpable
    End point type
    Secondary
    End point timeframe
    Time to disease progression was defined as time from date of consent to date of progression, last follow up or death (whichever occurs first). Patients who die and do not progress are censored at the date of death/last follow up.
    End point values
    		 HLA A2 positive HLA A2 Negative ITT population
    Number of subjects analysed
    13 [9]
    9 [10]
    22 [11]
    Units: Months
        median (confidence interval 90%)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    Attachments
    		 Kaplan-Meier for time to progression or death
    Notes
    [9] - No events observed therefore median and CI not reached
    [10] - No events observed therefore median and CI not reached
    [11] - No events observed therefore median and CI not reached
    Statistical analysis title
    		 Cox proportional hazards regression
    Statistical analysis description
    No events observed so therefore no results were computed.
    Comparison groups
    HLA A2 positive v HLA A2 Negative v ITT population
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0 [12]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 1
    Notes
    [12] - No events observed so therefore no results were computed. Dummy values entered to satisfy upload

    Secondary: Time to next treatment

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    End point title
    		 Time to next treatment
    End point description
    A next treatment is defined as the first drug taken during the course of the study with an indication to treat CML.
    End point type
    Secondary
    End point timeframe
    Time to next treatment defined as time from date of consent to date of last follow up or next CML treatment (whichever occurs first). Patients who die or do not have a next treatment are censored at the date of death/last follow up.
    End point values
    		 HLA A2 positive HLA A2 Negative ITT population
    Number of subjects analysed
    13 [13]
    9 [14]
    22 [15]
    Units: Months
        median (confidence interval 90%)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    Attachments
    		 Kaplan-Meier for time to next treatment
    Notes
    [13] - No events observed therefore median and CI not reached
    [14] - No events observed therefore median and CI not reached
    [15] - No events observed therefore median and CI not reached
    Statistical analysis title
    		 Cox proportional hazard regression
    Statistical analysis description
    The reference category for the Hazard Ratio is HLA A2 - patients i.e. a hazard ratio greater than 1 represents a favourable outcome for HLA A2 - patients; a hazard ratio below 1 represents a favourable outcome for HLA A2 + patients No results were computed as no events were observed.
    Comparison groups
    HLA A2 positive v HLA A2 Negative v ITT population
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0 [16]
    Method
    		 Not done
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 1
    Notes
    [16] - No results were computed as no events were observed. dummy value entered to satisfy upload

    Secondary: Time to BCR-ABL response (major or minor or CMR) from the beginning of tyrosine kinase inhibitor treatment

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    End point title
    		 Time to BCR-ABL response (major or minor or CMR) from the beginning of tyrosine kinase inhibitor treatment
    End point description
    Patients who did not respond were censored at the date of last BCR-ABL response.
    End point type
    Secondary
    End point timeframe
    Time to BCR-ABL response in years is defined as time from date of beginning tyrosine kinase inhibitor treatment to date of last BCR-ABL sample or the first date of BCR-ABL response (whichever occurs first).
    End point values
    		 HLA A2 positive HLA A2 Negative Molecular analysis set
    Number of subjects analysed
    12 [17]
    8 [18]
    20 [19]
    Units: Years
        median (confidence interval 90%)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    Attachments
    		 Kaplan-Meier plot
    Notes
    [17] - The number in the molecular analysis population
    [18] - The number in the molecular analysis population
    [19] - Median and CI were not reached due to small number of events
    Statistical analysis title
    		 Cox proportional hazards model
    Statistical analysis description
    The reference category for the Hazard Ratio is HLA A2 - patients i.e. a hazard ratio greater than 1 represents a favourable outcome for HLA A2 - patients; a hazard ratio below 1 represents a favourable outcome for HLA A2 + patients
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 = 0.77
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.661
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.064
         upper limit
    		 6.782
    Notes
    [20] - Median time and its 90% confidence interval were not reached because a small number of events were observed.
    Statistical analysis title
    		 Logrank test
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.768
    Method
    		 Logrank
    Confidence interval

    Secondary: Time to BCR-ABL response (major or minor or CMR) from date of informed consent

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    End point title
    		 Time to BCR-ABL response (major or minor or CMR) from date of informed consent
    End point description
    End point type
    Secondary
    End point timeframe
    Time to BCR-ABL response in months is defined as time from date of consent to date of last BCR-ABL sample or the first date of BCR-ABL response (whichever occurs first). Patients who did not respond were censored at the date of last BCR-ABL response.
    End point values
    		 HLA A2 positive HLA A2 Negative Molecular analysis set
    Number of subjects analysed
    12 [21]
    8 [22]
    20 [23]
    Units: Months
        median (confidence interval 90%)
    0 (0 to 0)
    22.8 (22.8 to 100)
    22.8 (22.8 to 100)
    Attachments
    		 Kaplan-Meier plot
    Notes
    [21] - Number in molecular analysis population Median & CI not reached
    [22] - Number in molecular analysis population Median & CI not reached
    [23] - Median and upper CI not reached due to small number of events.
    Statistical analysis title
    		 Cox proportional hazard regression
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.699
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.577
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.056
         upper limit
    		 5.947
    Statistical analysis title
    		 Logrank test
    Comparison groups
    HLA A2 Negative v HLA A2 positive v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.695
    Method
    		 Logrank
    Confidence interval

    Secondary: Time to WT1 response (major or minor or CMR) in years is defined as time from date of beginning tyrosine kinase inhibitor treatment

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    End point title
    		 Time to WT1 response (major or minor or CMR) in years is defined as time from date of beginning tyrosine kinase inhibitor treatment
    End point description
    Patients who did not respond were censored at the date of last WT1 response.
    End point type
    Secondary
    End point timeframe
    Time to WT1 response in years is defined as time from date of beginning tyrosine kinase inhibitor treatment to date of last WT1 sample or the first date of WT1 response (whichever occurs first).
    End point values
    		 HLA A2 positive HLA A2 Negative Molecular analysis set
    Number of subjects analysed
    12 [24]
    8 [25]
    20 [26]
    Units: Years
        median (confidence interval 90%)
    8 (8 to 100)
    8.7 (8.7 to 100)
    8.7 (8.7 to 100)
    Attachments
    		 Kaplan-Meier plot
    Notes
    [24] - Median and Upper CI not reached. numbers added for compliance. see KM plot
    [25] - Median and Upper CI not reached. numbers added for compliance. see KM plot
    [26] - Median and upper CI not reached due to small number of events. Numbers added for compliance
    Statistical analysis title
    		 Cox proportional hazard regression
    Statistical analysis description
    The reference category for the Hazard Ratio is HLA A2 - patients i.e. a hazard ratio greater than 1 represents a favourable outcome for HLA A2 - patients; a hazard ratio below 1 represents a favourable outcome for HLA A2 + patients
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.765
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.688
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.088
         upper limit
    		 5.397
    Statistical analysis title
    		 Logrank test
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.764
    Method
    		 Logrank
    Confidence interval

    Secondary: Time to WT1 response (major or minor or CMR) from date of informed consent

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    End point title
    		 Time to WT1 response (major or minor or CMR) from date of informed consent
    End point description
    Patients who did not respond were censored at the date of last WT1 response.
    End point type
    Secondary
    End point timeframe
    Time to WT1 response in months is defined as time from date of consent to date of last WT1 sample or the first date of WT1 response (whichever occurs first).
    End point values
    		 HLA A2 positive HLA A2 Negative Molecular analysis set
    Number of subjects analysed
    12 [27]
    8 [28]
    20 [29]
    Units: Months
        median (confidence interval 90%)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    Attachments
    		 Kaplan-Meier plot
    Notes
    [27] - Number in the molecular analysis population
    [28] - Number in the molecular analysis population
    [29] - Median and CI not reached due to small number of events.
    Statistical analysis title
    		 Cox proportional hazards regression
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.879
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.205
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.161
         upper limit
    		 9.05
    Statistical analysis title
    		 Logrank test
    Comparison groups
    HLA A2 positive v HLA A2 Negative v Molecular analysis set
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.879
    Method
    		 Logrank
    Confidence interval

    Secondary: Overall survival

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    End point title
    		 Overall survival
    End point description
    End point type
    Secondary
    End point timeframe
    OS defined as time from date of consent to date of last follow up or death (whichever occurs first). Patients who do not die are censored at the date of last follow up.
    End point values
    		 HLA A2 positive HLA A2 Negative ITT population
    Number of subjects analysed
    13
    9
    22 [30]
    Units: Months
        median (confidence interval 90%)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    Attachments
    		 Kaplan-Meier plot
    Notes
    [30] - Median and CI not reached due to no events observed.
    Statistical analysis title
    		 Cox proportional hazard regression
    Statistical analysis description
    No events observed so therefore no results were computed.
    Comparison groups
    HLA A2 positive v HLA A2 Negative v ITT population
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0 [31]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 1
    Notes
    [31] - No events observed so therefore no results were computed.

    Secondary: Pain assessment immediately after vaccination (How severe is your pain or discomfort now?)

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    End point title
    		 Pain assessment immediately after vaccination (How severe is your pain or discomfort now?) [32]
    End point description
    Pain and discomfort data were collected on a visual analogue scale ranging from 0 (no pain/discomfort) to 10 (worst ever pain/discomfort). Median score for each pain assessment question obtained by calculating the summary statistics using the median score for the corresponding pain assessment question recorded for each patient across all vaccination visits .
    End point type
    Secondary
    End point timeframe
    Recorded immediately after vaccination
    Notes
    [32] - 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: Pain assessment information recorded immediately after vaccination and recorded 48 hours post vaccination were summarised in terms of the median pain score recorded and the worst pain score recorded for HLA A2+ patients in the ITT population only.
    End point values
    		 HLA A2 positive
    Number of subjects analysed
    12 [33]
    Units: Score from 0 (none) to 10 (worst)
        median (inter-quartile range (Q1-Q3))
    1 (1 to 2.3)
    Notes
    [33] - One patient did not receive any treatment and therefore was not included in summary.
    No statistical analyses for this end point

    Secondary: Pain assessment immediately after vaccination (How severe was your pain or discomfort during and immediately after the injection?)

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    End point title
    		 Pain assessment immediately after vaccination (How severe was your pain or discomfort during and immediately after the injection?) [34]
    End point description
    Pain and discomfort data were collected on a visual analogue scale ranging from 0 (no pain/discomfort) to 10 (worst ever pain/discomfort). Median score for each pain assessment question obtained by calculating the summary statistics using the median score for the corresponding pain assessment question recorded for each patient across all vaccination visits .
    End point type
    Secondary
    End point timeframe
    Assessment completed immediately post-vaccination
    Notes
    [34] - 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: Pain assessment information recorded immediately after vaccination and recorded 48 hours post vaccination were summarised in terms of the median pain score recorded and the worst pain score recorded for HLA A2+ patients in the ITT population only.
    End point values
    		 HLA A2 positive
    Number of subjects analysed
    12 [35]
    Units: Score from 0 (none) to 10 (worst)
        median (inter-quartile range (Q1-Q3))
    3 (2 to 5)
    Notes
    [35] - One patient did not receive any treatment and therefore was not included in summary.
    No statistical analyses for this end point

    Secondary: Pain assessment immediately after vaccination (How distressing is your pain or discomfort now?)

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    End point title
    		 Pain assessment immediately after vaccination (How distressing is your pain or discomfort now?) [36]
    End point description
    Pain and discomfort data were collected on a visual analogue scale ranging from 0 (no pain/discomfort) to 10 (worst ever pain/discomfort). Median score for each pain assessment question obtained by calculating the summary statistics using the median score for the corresponding pain assessment question recorded for each patient across all vaccination visits .
    End point type
    Secondary
    End point timeframe
    Assessment completed immediately post-vaccination
    Notes
    [36] - 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: Pain assessment information recorded immediately after vaccination and recorded 48 hours post vaccination were summarised in terms of the median pain score recorded and the worst pain score recorded for HLA A2+ patients in the ITT population only.
    End point values
    		 HLA A2 positive
    Number of subjects analysed
    12 [37]
    Units: Score from 0 (none) to 10 (worst)
        median (inter-quartile range (Q1-Q3))
    1 (0.3 to 1)
    Notes
    [37] - One patient did not receive treatment and therefore was excluded from summary.
    No statistical analyses for this end point

    Secondary: Pain assessment immediately after vaccination (How distressing was your pain or discomfort during and immediately after the injection?)

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    End point title
    		 Pain assessment immediately after vaccination (How distressing was your pain or discomfort during and immediately after the injection?) [38]
    End point description
    Pain and discomfort data were collected on a visual analogue scale ranging from 0 (no pain/discomfort) to 10 (worst ever pain/discomfort). Median score for each pain assessment question obtained by calculating the summary statistics using the median score for the corresponding pain assessment question recorded for each patient across all vaccination visits .
    End point type
    Secondary
    End point timeframe
    Assessment completed immediately post-vaccination
    Notes
    [38] - 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: Pain assessment information recorded immediately after vaccination and recorded 48 hours post vaccination were summarised in terms of the median pain score recorded and the worst pain score recorded for HLA A2+ patients in the ITT population only.
    End point values
    		 HLA A2 positive
    Number of subjects analysed
    12 [39]
    Units: Score from 0 (none) to 10 (worst)
        median (inter-quartile range (Q1-Q3))
    2.3 (1 to 4)
    Notes
    [39] - One patient did not receive treatment and therefore was excluded from summary.
    No statistical analyses for this end point

    Secondary: Pain assessment 48 hours post-vaccination (Pain at its worst in the last 48 hours?)

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    End point title
    		 Pain assessment 48 hours post-vaccination (Pain at its worst in the last 48 hours?) [40]
    End point description
    Pain and discomfort data were collected on a visual analogue scale ranging from 0 (no pain/discomfort) to 10 (worst ever pain/discomfort). Median score for each pain assessment question obtained by calculating the summary statistics using the median score for the corresponding pain assessment question recorded for each patient across all vaccination visits .
    End point type
    Secondary
    End point timeframe
    Assessment completed 48 hours post-vaccination
    Notes
    [40] - 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: Pain assessment information recorded immediately after vaccination and recorded 48 hours post vaccination were summarised in terms of the median pain score recorded and the worst pain score recorded for HLA A2+ patients in the ITT population only.
    End point values
    		 HLA A2 positive
    Number of subjects analysed
    12 [41]
    Units: Score from 0 (none) to 10 (worst)
        median (inter-quartile range (Q1-Q3))
    0.5 (0 to 1)
    Notes
    [41] - One patient did not receive treatment and therefore was excluded from summary.
    No statistical analyses for this end point

    Secondary: Pain assessment 48 hours post-vaccination (Pain at its least in the last 48 hours?)

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    End point title
    		 Pain assessment 48 hours post-vaccination (Pain at its least in the last 48 hours?) [42]
    End point description
    Pain and discomfort data were collected on a visual analogue scale ranging from 0 (no pain/discomfort) to 10 (worst ever pain/discomfort). Median score for each pain assessment question obtained by calculating the summary statistics using the median score for the corresponding pain assessment question recorded for each patient across all vaccination visits .
    End point type
    Secondary
    End point timeframe
    Assessment completed 48 hours post-vaccination
    Notes
    [42] - 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: Pain assessment information recorded immediately after vaccination and recorded 48 hours post vaccination were summarised in terms of the median pain score recorded and the worst pain score recorded for HLA A2+ patients in the ITT population only.
    End point values
    		 HLA A2 positive
    Number of subjects analysed
    12 [43]
    Units: Score from 0 (none) to 10 (worst)
        median (inter-quartile range (Q1-Q3))
    0 (0 to 0)
    Notes
    [43] - One patient did not receive treatment and therefore was excluded from summary.
    No statistical analyses for this end point

    Secondary: Pain assessment 48 hours post-vaccination (Pain at its average in the last 48 hours?)

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    End point title
    		 Pain assessment 48 hours post-vaccination (Pain at its average in the last 48 hours?) [44]
    End point description
    Pain and discomfort data were collected on a visual analogue scale ranging from 0 (no pain/discomfort) to 10 (worst ever pain/discomfort). Median score for each pain assessment question obtained by calculating the summary statistics using the median score for the corresponding pain assessment question recorded for each patient across all vaccination visits .
    End point type
    Secondary
    End point timeframe
    Assessment completed 48 hours post-vaccination
    Notes
    [44] - 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: Pain assessment information recorded immediately after vaccination and recorded 48 hours post vaccination were summarised in terms of the median pain score recorded and the worst pain score recorded for HLA A2+ patients in the ITT population only.
    End point values
    		 HLA A2 positive
    Number of subjects analysed
    12 [45]
    Units: Score from 0 (none) to 10 (worst)
        median (inter-quartile range (Q1-Q3))
    0.3 (0 to 1)
    Notes
    [45] - One patient did not receive treatment and therefore was excluded from summary.
    No statistical analyses for this end point

    Secondary: Pain assessment 48 hours post-vaccination (How much pain you have right now?)

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    End point title
    		 Pain assessment 48 hours post-vaccination (How much pain you have right now?) [46]
    End point description
    Pain and discomfort data were collected on a visual analogue scale ranging from 0 (no pain/discomfort) to 10 (worst ever pain/discomfort). Median score for each pain assessment question obtained by calculating the summary statistics using the median score for the corresponding pain assessment question recorded for each patient across all vaccination visits .
    End point type
    Secondary
    End point timeframe
    Assessment completed 48 hours post-vaccination
    Notes
    [46] - 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: Pain assessment information recorded immediately after vaccination and recorded 48 hours post vaccination were summarised in terms of the median pain score recorded and the worst pain score recorded for HLA A2+ patients in the ITT population only.
    End point values
    		 HLA A2 positive
    Number of subjects analysed
    12 [47]
    Units: Score from 0 (none) to 10 (worst)
        median (inter-quartile range (Q1-Q3))
    0 (0 to 0)
    Notes
    [47] - One patient did not receive treatment and therefore was excluded from summary.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events were reported for the entire trial period. The reporting requirement for SAEs affecting subjects applies for all events which occurred up to 4 weeks after the last administration of study drugs
    Adverse event reporting additional description
    Adverse events were assessed during every patient visit.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 NCI CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    HLA A2 positive safety population
    Reporting group description
    		 Intervention group: all eligible, consenting CML patients who were HLA A2 positive and received at least one trial drug administration

    Reporting group title
    HLA A2 Negative
    Reporting group description
    		 Control group: all eligible and consenting patients who were HLA A2 negative

    Serious adverse events
    		 HLA A2 positive safety population HLA A2 Negative
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 HLA A2 positive safety population HLA A2 Negative
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 12 (100.00%)
    9 / 9 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Edema limbs
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Fatigue
         subjects affected / exposed
    4 / 12 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    5
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 9 (22.22%)
         occurrences all number
    1
    2
    Epistaxis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders, Other
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Investigations
    CPK increased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Bruising
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Injury, poisoning and procedural complications, Other
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    4
    Nervous system disorders, Other
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 9 (22.22%)
         occurrences all number
    1
    2
    Ear and labyrinth disorders
    Ear and labyrinth disorders, Other
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Eye disorders, Other
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Watering eyes
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Bloating
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Dyspepsia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders, Other
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Skin ulceration
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Renal and urinary disorders, Other
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Renal calculi
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Urinary tract pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Musculoskeletal and connective tissue disorders, Other
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    3 / 12 (25.00%)
    0 / 9 (0.00%)
         occurrences all number
    6
    0
    Pain in extremity
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Eye infection
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Nail infection
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Upper respiratory infection
         subjects affected / exposed
    2 / 12 (16.67%)
    5 / 9 (55.56%)
         occurrences all number
    2
    6
    Metabolism and nutrition disorders
    Anorexia
    alternative dictionary used: CTCAE 4.0
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Sep 2010
    Addition of electrocardiogram at baseline; Logistical changes made for supply and return of IMP; Clarification on monitoring.
    01 Nov 2010
    Update in the Investigational Medicinal Product Dossier included in the protocol.
    12 Aug 2011
    Clarification of patient pathway throughout the trial from consent; clarification on the schedule of observations and procedure for HLA negative participants; clarification on inclusion criteria for AML patients with regards to WT1 status; clarification determination of bone status for trial inclusion; clarification on resupply of IMP to sites; clarification of local and central laboratory responsibilities and shipment of samples; amendment of pain assessment Case Report Form to remove patient identifiers; addition of DTH (delayed type hypersensitivity) reaction to be carried out wherever feasible.
    16 Jan 2012
    Eligibility criteria amended to allow patients with a 6 months history of lymphocyte counts of just below 1 to be included in the trial.
    17 May 2012
    Stability data for pDOM WT1 DNA vaccines to support the proposed expiry date extension plan at the predetermined 18 month time point.
    08 Nov 2012
    Eligibility criteria widened to include all tyrosine kinase inhibitors to increase recruitment; Change in trial design from a two stage design to a single stage design; sample size adjusted to 32 CML patients and 37 AML patients; All HLA A2+ patients to receive all 12 vaccinations instead of only receiving the latter 6 if a response is observed.
    07 Nov 2013
    Patients last follow 12 months post final vaccination. ELISPOT removed from endpoint analysis (replaced by tetramer staining). 36 month follow-up visit removed.
    03 Apr 2014
    End of Trial Notification

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    11 Apr 2013
    CML arm of the trial stopped and temporary halt on trial for AML arm.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study did not complete recruitment as per the sample size.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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