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    Clinical Trial Results:
    A Two-Stage Phase II Study of Autologous TriMix-DC Therapeutic Vaccine in Combination with Ipilimumab in Patients with Previously Treated Unresectable Stage III or IV Melanoma.

    Summary
    EudraCT number
    		 2010-023058-35
    Trial protocol
    		 BE  
    Global end of trial date
    01 Jun 2015

    Results information
    Results version number
    		 v2(current)
    This version publication date
    02 Oct 2021
    First version publication date
    09 Apr 2021
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    End date of trial 31DEC2016
    Summary report(s)
    		 Wilgenhof et al JCO article

    Trial information

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    Trial identification
    Sponsor protocol code
    UZB-VUB-10-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01302496
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    UZ Brussel
    Sponsor organisation address
    Laarbeeklaan 101, Jette, Belgium, 1090
    Public contact
    Bart Neyns, UZ Brussel, 0032 24775447, bart.neyns@uzbrussel.be
    Scientific contact
    Bart Neyns, UZ Brussel, 0032 24775447, bart.neyns@uzbrussel.be
    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
    01 Jun 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Nov 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Jun 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To estimate the anti-tumor activity of therapeutic vaccination with autologous TriMix-DC vaccine in combination with ipilimumab in patients with previously treated, therapy-refractory or -intolerant, unresectable, AJCC Stage III or Stage IV melanoma.
    Protection of trial subjects
    Signed Informed consent, in this consent is explained that the patient data is anonymized. Safety data will be collected on a continuous basis and will be reviewed by the Sponsor in order to ensure that it is appropriate to continue the study
    Background therapy
    		 NA
    Evidence for comparator
    		 NA
    Actual start date of recruitment
    02 May 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 18 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 39
    Worldwide total number of subjects
    39
    EEA total number of subjects
    39
    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)
    32
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients with histologically confirmed, unresectable, American Joint Committee on Cancer (AJCC) stage III or IV melanoma with measurable disease, who experienced treatment failure with at least one prior line of systemic treatment, were eligible.

    Pre-assignment
    Screening details
    		 Willing and able to give written informed consent Histologically confirmed malignant melanoma Measurable melanoma AJCC Stage III (unresectable) or Stage IV melanoma Response to treatment with at least one prior regimen (non-experimental or experimental) with the exception of a CD137 agonist

    Pre-assignment period milestones
    Number of subjects started
    		 39
    Number of subjects completed
    		 39

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

    Arms
    Arm title
    		 TriMixDC-MEL plus Ipilimumab
    Arm description
    		 Single arm study
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ipilimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ipilimumab 10mg/kg every 3 weeks x4 followed by 1 administration Q12 weeks

    Investigational medicinal product name
    TriMixDC-MEL
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intravenous use
    Dosage and administration details
    TriMixDC-MEL suspension administered every 3 weeks

    Number of subjects in period 1
    		TriMixDC-MEL plus Ipilimumab
    Started
    39
    Completed
    39

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment
    Reporting group description
    		 Single arm study, treatment arm

    Reporting group values
    		 Treatment Total
    Number of subjects
    		 39 39
    Age categorical
    Adults (18-64years) From 65-84years
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 32 32
        From 65-84 years
    		 7 7
        85 years and over
    		 0 0
    Age continuous
    Median Age 46years, (range 24-70years)
    Units: years
        median (full range (min-max))
    		 46 (24 to 70) -
    Gender categorical
    Units: Subjects
        Female
    		 16 16
        Male
    		 23 23

    End points

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    End points reporting groups
    Reporting group title
    TriMixDC-MEL plus Ipilimumab
    Reporting group description
    		 Single arm study

    Subject analysis set title
    Single arm study
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Single arm study

    Subject analysis set title
    Single arm study
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Single arm study, fantom arm to resolve the query

    Primary: The 6-month disease control

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    End point title
    		 The 6-month disease control
    End point description
    The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post–DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event.
    End point type
    Primary
    End point timeframe
    The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses)
    End point values
    		 TriMixDC-MEL plus Ipilimumab Single arm study Single arm study
    Number of subjects analysed
    39 [1]
    39
    39 [2]
    Units: whole
    39
    39
    39
    Notes
    [1] - Singel arm study
    [2] - fantom arm
    Statistical analysis title
    		 ORR% estimate
    Statistical analysis description
    A Simon two-stage design (minimax) was used to test the null hypothesis that the DCR at 6 months was<33% versus the alternative hypothesis that the DCR at 6 months was > 50%. Using an a error of .05 and a b error of .20, a DCR by irRC at 6 months of greater than seven of 19 patients was needed to continue the study and recruit a final total of 39 patients.
    Comparison groups
    TriMixDC-MEL plus Ipilimumab v Single arm study v Single arm study
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    Method
    Parameter type
    		 ORR%
    Point estimate
    51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 36
         upper limit
    		 67
    Variability estimate
    Standard deviation
    Notes
    [3] - single arm phase II study

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Throughout the duration of the study Clinical and blood parameters were assessed every 3 weeks. Adverse events (AEs) were graded for severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4
    Reporting groups
    Reporting group title
    Study population
    Reporting group description
    		 All the 39 patients that entered the study

    Serious adverse events
    		 Study population
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 39 (0.00%)
         number of deaths (all causes)
    26
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Study population
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    39 / 39 (100.00%)
    Nervous system disorders
    Hypophysitis
    Additional description: Immune related AE; Grade II
         subjects affected / exposed
    6 / 39 (15.38%)
         occurrences all number
    6
    General disorders and administration site conditions
    Skin injection site reaction
    Additional description: Dendritic cells related AE; Grade II skin injection site reaction
         subjects affected / exposed
    39 / 39 (100.00%)
         occurrences all number
    39
    Flu-like symptoms
    Additional description: Dendritic cells related AE; Grade II (<72h post administration)
         subjects affected / exposed
    33 / 39 (84.62%)
         occurrences all number
    33
    Gastrointestinal disorders
    Colitis
    Additional description: Imune related AE; Colitis/diarrhea grade II/II
         subjects affected / exposed
    8 / 39 (20.51%)
         occurrences all number
    8
    Hepatobiliary disorders
    Hepatitis
    Additional description: Immune related AE; Grade III/IV
         subjects affected / exposed
    5 / 39 (12.82%)
         occurrences all number
    5
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis
    Additional description: Immune related AE; Grade III
         subjects affected / exposed
    3 / 39 (7.69%)
         occurrences all number
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

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