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
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EudraCT number |
2010-023058-35 |
Trial protocol |
BE |
Global end of trial date |
01 Jun 2015
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Results information
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Results version number |
v2(current) |
This version publication date |
02 Oct 2021
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First version publication date |
09 Apr 2021
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Other versions |
v1 |
Version creation reason |
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Summary report(s) |
Wilgenhof et al JCO article |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
UZB-VUB-10-001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01302496 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
UZ Brussel
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Sponsor organisation address |
Laarbeeklaan 101, Jette, Belgium, 1090
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Public contact |
Bart Neyns, UZ Brussel, 0032 24775447, bart.neyns@uzbrussel.be
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Scientific contact |
Bart Neyns, UZ Brussel, 0032 24775447, bart.neyns@uzbrussel.be
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Jun 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Nov 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Jun 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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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.
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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
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Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
02 May 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
18 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 39
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Worldwide total number of subjects |
39
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EEA total number of subjects |
39
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
32
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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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
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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
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Number of subjects started |
39 | ||||||
Number of subjects completed |
39 | ||||||
Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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TriMixDC-MEL plus Ipilimumab | ||||||
Arm description |
Single arm study | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Ipilimumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ipilimumab 10mg/kg every 3 weeks x4 followed by 1 administration Q12 weeks
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Investigational medicinal product name |
TriMixDC-MEL
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intravenous use
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Dosage and administration details |
TriMixDC-MEL suspension administered every 3 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
Single arm study, treatment arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
TriMixDC-MEL plus Ipilimumab
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Reporting group description |
Single arm study | ||
Subject analysis set title |
Single arm study
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Single arm study
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Subject analysis set title |
Single arm study
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Single arm study, fantom arm to resolve the query
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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.
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End point type |
Primary
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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)
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Notes [1] - Singel arm study [2] - fantom arm |
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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.
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Comparison groups |
TriMixDC-MEL plus Ipilimumab v Single arm study v Single arm study
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Number of subjects included in analysis |
117
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | ||||||||||||
Method |
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Parameter type |
ORR% | ||||||||||||
Point estimate |
51
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
36 | ||||||||||||
upper limit |
67 | ||||||||||||
Variability estimate |
Standard deviation
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Notes [3] - single arm phase II study |
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Adverse events information
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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).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Study population
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Reporting group description |
All the 39 patients that entered the study | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |