The overall purpose of the study is to investigate the efficacy and safety of ALECSAT in GBM patients either with relapse of GBM after first line treatments (followed by reoperation if possible). The efficacy and safety of ALECSAT treatment is, compared to standard Avastin/Irinotecan econd line treatments for these patients. MedDRA version: 17.0 Level: PT Classification code 10018337 Term: Glioblastoma multiforme System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl c
Conditions
Interventions
Product Name: ALECSAT
Product Code: PR1
Pharmaceutical Form: Suspension for injection
Trade Name: Bevacizumab and Irinotecan in combination
Pharmaceutical Form: Concentrate and solvent for concentrat
Sponsors
CytoVac A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The patients must meet the following criteria in order to be eligible for inclusion in the study: 1. Histologically confirmed GBM tumour with recurrence during or after completing the first-line treatments, documented by MRI 2. Minimum age of 18 years old Capable of understanding the information and giving informed consent 3. Minimum height of 155 cm 1. Expected survival time (life expectancy) of over 3 months 2. Adequate performance status £ 2 (see below*) 3. Clinically normal EVF 4. Women in fertile conditions can only be included with a negative pregnancy test at screening and must use appropriate contraceptives during the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: Criteria which exclude the patient for entering in the study are: 1. Positive tests for anti-HIV-1/2; HBsAg, anti-HBc, Anti-HCV or being positive in a Treponema Pallidum test (syphilis) 2. Patients which have visit an area where there is an outbreak of West Nile virus or Dengue virus within 28 days prior to donation should be excluded, unless the patient has been tested negative 3. Concurrent illness, e.g. uncontrolled epilepsy, cardiovascular-, cerebrovascular-, and/or respiratory disease which can worsen or cause complications in connection with blood donation 4. Clinically significant autoimmune disorders or conditions of immune suppression 5. Hemoglobin count = 7.5mmol/l (men & women) 6. Lymphocyte-numbers below 0.5 x 109/l 7. Body weight below 40 kg (men) and 50 kg (women) 8. Clinically abnormal ECG as judged by the Investigator 9. Pregnant or breast feeding women 10. Inclusion in other clinical studies 4 weeks prior to inclusion in the study 11. Any medical condition that will render participation in the study risky or, according to the Investigator will make the assessment of the study endpoints difficult 12. Treatment with any immunotherapy, cytotoxic therapy or, biologic therapy 4 weeks prior to enrolment in this study 13. Patienys that either put a risk due to the blood donation or where it is not expected taht an ALECSAT product of good quality van be produced 14. Patients with uncontrolled serious bacterial, viral , fungal or parasitic infection 15. Blood transfusion within 48 hours prior to donation of blood for LECSAT production 16Known or suspected intolerance to Avastin, Irinotecan or any of the excipients as well as intolerance to recombiant humanized antibodies 17. Performance status >3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare progression free survival (PFS) in patients with relapsed GBM when the patients are either treated with ALECSAT immunotherapy or standard praxis therapy with Avastin/Irinotecan.The included patients disease has relapsed during or after receceiving recongnized first-line treatments. Progression of disease is defined according to the response ecaluation criteria for solid (RANO);Secondary Objective: • To evaluate the overall survival (OS) during the study period in patients treated with ALECSAT compared to patients treated with Avastin/Irinotecan by Kaplan-Meier methodology • To evaluate time to progression in the two treatment groups • To compare PFS in the two treatment groups by Kaplan-Meier methodology • To compare PFS in a landmark analysis in the two treatment groups after a duration of 6 and 12 months after initiation of treatment • To compare ORR • To investigate QoL and performance status during the study period for patients treated with ALECSAT compared to patients treated with Avastin/Irinotecan • To investigate any changes in leucocytes and lymphocytes during the study period for patients receiving ALECSAT • To investigate radiological changes as measured by MRI during the study period for the ALECSAT group and compare the results with the Avastin/Irinotecan treated group ;Primary end point(s): • PFS, progreesion-free survival, measured by MRI according to RANO at specific time points during the study period, to be analysed when top-line data are obtained after 124 PFS events or after LSLV in case of the total number of PFS events ending up being less that 124;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Endpoints • OS (Overall Survival), the number of patients still alive at the end of study (EoS) • Time to progression • PFS time to event analysis (Kaplan-Meier) upon study completion, inthe cases of topline results after 124 evebts published before LSLV •PFS landmark after duration of 6 month from initiation of treatment as measured by MRI according to RANO at specific time points during the study period • • PFS landmark at 12 months • ORR (Objective Response Rate) defined as the response rate of patients having a complete (CR) or partial response (PR) within the two treatment groups • Evaluate outcome of patients response to QoL questionnaire (Appendix 3) and performance status in the two treatment groups at specific time points during the study period • Changes in leucocytes and lymphocytes in the ALECSAT arm at specific time points during the study period. • Changes in tumour size measured by MRI Safety Endpoints • Comparison of type and frequency of AEs • Changes in biochemical parameters of clinical relevance • Changes in hematology parameters of clinical relevance • Changes in vital signs • Evaluation of medical events of special interest • Changes in electrocardiogram (ECG) Exploratory Endpoints • Use of corticosteroid for each patient during study • Differences in level and variability between the tumour measurements provided by Investigator and by the blinded radiologist • To compare the two groups with respect to reoperation / no reoperation, tumour size, histo-pathologic diagnosis and genomic diagnosis using O6-methylguanine-DNAmethyltransferase (MGMT) at the time of allocation in the study • Changes in tumour size measured by 18F-FET/PET (PET only at sites having PET equipment) ;Timepoint(s) of evaluation of this end point: At specific time points during the study period | — |
Countries
Denmark
Contacts
Public ContactClinical Trials Information
CytoVac A/S
Outcome results
None listed