Clinical Trial Results:
PROSPECTIVE, PHASE II CLINICAL TRIAL TO EVALUATE EFFICACY AND SAFETY OF AUTOLOGOUS DENDRITIC CELL VACCINATION IN
GLIOBLASTOMA MULTIFORME PATIENTS AFTER COMPLETE SURGICAL RESECTION WITH FLUORESCENCE MICROSCOPE
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Summary
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EudraCT number |
2009-009879-35 |
Trial protocol |
ES |
Global end of trial date |
01 Aug 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Sep 2021
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First version publication date |
19 Sep 2021
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Other versions |
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Summary report(s) |
SPANISH REPORT |
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 |
DEND/GM
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01006044 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Clínica Universidad de Navarra
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Sponsor organisation address |
Avda. Pío XII, 36, Pamplona, Spain, 31008
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Public contact |
UCICEC, Clínica Universidad de Navarra, 34 948 255 400 114, ucicec@unav.es
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Scientific contact |
UCICEC, Clínica Universidad de Navarra, 34 948 255 400 1148, ucicec@unav.es
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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 |
18 Apr 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Aug 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Aug 2014
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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 |
Assessing the impact of treatment on progression-free survival.
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Protection of trial subjects |
NA
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Oct 2009
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Long term follow-up planned |
No
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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 |
Spain: 26
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Worldwide total number of subjects |
26
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EEA total number of subjects |
26
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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) |
19
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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 between 18 and 70 years old, with a histological diagnosis of glioblastoma who have not previously been treated with chemo- or radiotherapy. After obtaining the patient's consent, surgery is performed where the tumour sample is processed. | ||||||||||||||||||
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Pre-assignment
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Screening details |
After surgery, early monitoring of the resection will be carried out with DG-MRI in the first 72h. If the residual volume is less than 1 cm3, the screening tests will be completed, and, if applicable, the patient's entry into the clinical trial shall be confirmed. Availability of sufficient tumour tissue processed to produce cell-based vaccines. | ||||||||||||||||||
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Period 1
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Period 1 title |
Teatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Treatment group | ||||||||||||||||||
Arm description |
26 patients were included in the trial. One patient withdrew consent and another patient died before receiving treatment, resulting in 24 patients receiving treatment. After surgery, standard treatment with concurrent radiotherapy and temozolomide was started, followed by twelve cycles of Temozolamide. In addition, autologous dendritic cells were obtained by leukapheresis and cell culture to prepare individualised cell vaccines. Each patient was given 4 monthly vaccinations, 4 bimonthly vaccinations and then 4 quarterly vaccinations. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
autologous dendritic cells
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
Leukapheresis of mononuclear cells is performed after completing a minimum of 7 days without steroid treatment. Immature dendritic cells are generated to prepare vaccines. The cell vaccine will be administered intradermally. The vaccination schedule shall begin as soon as possible after surgery. If possible, the first dose should be administered before starting radiotherapy. Repeat monthly until the first 4 vaccinations are completed. Thereafter, 4 vaccinations will be administered every other month and 4 quarterly. The total dose is 10 millones U unit(s).
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Arm title
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Historical control group | ||||||||||||||||||
Arm description |
The overall survival of the treatment group is compared to a historical control group. For historical control, a search was carried out in the CUN medical records system for patients operated on at the centre for glioblastoma since 2007, when fluorescence surgery was first used. 23 patients were selected who met the same inclusion criteria used in the clinical trial, had none of the exclusion criteria, and the clinical information included follow-up until death or up to 24 months. | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Treatment group
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Reporting group description |
26 patients were included in the trial. One patient withdrew consent and another patient died before receiving treatment, resulting in 24 patients receiving treatment. After surgery, standard treatment with concurrent radiotherapy and temozolomide was started, followed by twelve cycles of Temozolamide. In addition, autologous dendritic cells were obtained by leukapheresis and cell culture to prepare individualised cell vaccines. Each patient was given 4 monthly vaccinations, 4 bimonthly vaccinations and then 4 quarterly vaccinations. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Historical control group
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Reporting group description |
The overall survival of the treatment group is compared to a historical control group. For historical control, a search was carried out in the CUN medical records system for patients operated on at the centre for glioblastoma since 2007, when fluorescence surgery was first used. 23 patients were selected who met the same inclusion criteria used in the clinical trial, had none of the exclusion criteria, and the clinical information included follow-up until death or up to 24 months. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treatment group
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Reporting group description |
26 patients were included in the trial. One patient withdrew consent and another patient died before receiving treatment, resulting in 24 patients receiving treatment. After surgery, standard treatment with concurrent radiotherapy and temozolomide was started, followed by twelve cycles of Temozolamide. In addition, autologous dendritic cells were obtained by leukapheresis and cell culture to prepare individualised cell vaccines. Each patient was given 4 monthly vaccinations, 4 bimonthly vaccinations and then 4 quarterly vaccinations. | ||
Reporting group title |
Historical control group
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Reporting group description |
The overall survival of the treatment group is compared to a historical control group. For historical control, a search was carried out in the CUN medical records system for patients operated on at the centre for glioblastoma since 2007, when fluorescence surgery was first used. 23 patients were selected who met the same inclusion criteria used in the clinical trial, had none of the exclusion criteria, and the clinical information included follow-up until death or up to 24 months. | ||
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End point title |
Survival | |||||||||||||||
End point description |
Patient survival is assessed with data of Progresion free survival (PFS) and Overall Survival (OS). Overall survival of the treated group is compared to a historical control group. For historical control group, a search was carried out in the CUN medical records system for patients operated on at the centre for glioblastoma since 2007, when fluorescence surgery was first used.
The addition of tumor lysate-pulsed autologous DCs vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide is feasible and safe. Its potential benefit in survival in such a selected population still needs to be confirmed in a randomized trial.
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End point type |
Primary
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End point timeframe |
The Survival is assessed during all the trial.
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Statistical analysis title |
Kaplan-Meier. Cox-regression | |||||||||||||||
Statistical analysis description |
Overall survival of the treated group is compared to a historical control group.
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Comparison groups |
Treatment group v Historical control group
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Number of subjects included in analysis |
47
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | |||||||||||||||
P-value |
< 0.05 | |||||||||||||||
Method |
Regression, Cox | |||||||||||||||
Confidence interval |
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| Notes [1] - When comparing overall survival between the treatment group and the historical control group using the Wilcoxon test, a p=0.03 was obtained. |
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Adverse events information
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Timeframe for reporting adverse events |
All OA occurring during the treatment period or within 30 days after the administration of the last dose of the protocol treatment should be recorded. SAEs must be reported by filling in the SAE form within 24 hours of becoming aware of the SAE.
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Adverse event reporting additional description |
No serious adverse events related to the study medication occur. Non-serious adverse events occur in all patients, but most of these are related to concomitant treatment, pharmacological or surgical, as well as to disease progression, not with study medication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
ND | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
ND
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Reporting groups
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Reporting group title |
treatment group
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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07 Oct 2009 |
Changes to clarify vaccine administration, correct errors and add partners. |
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07 Oct 2009 |
Include model of oral consent of the patient in the presence of witnesses.
Clarify that the administration of GM CSF and interferon alpha will be at the discretion of the investigator.
Modify initial application form |
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28 Mar 2012 |
Add intermediate data analysis |
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13 Jun 2012 |
Change of promoter |
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21 Sep 2012 |
Change of principal investigator, due to death. |
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26 Jun 2013 |
Changes on the IMPD |
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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 | |||
