Back to resultsRandomized Phase 2 Study to Investigate Efficacy of ALECSAT in Patients With GBM Measured Compared to Avastin/Irinotecan
Primary Purpose
Glioblastoma Multiforme
Status
Terminated
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
ALECSAT
Bevacizumab/Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma multiforme, Immunotherapy, Bevacizumab/Irinotecan, ALECSAT, recurrent
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed GBM tumour with recurrence during or after completing the recognized first-line treatments, tumor recurrence, documented by MRI,
- Minimum age of 18 years old,
- Capable of understanding the information and giving informed consent
- Minimum height of 155 cm
- Expected survival time (life expectancy) of over 3 months
- Adequate performance status equal or below 2
- Clinically normal Erythrocyte Volume Fraction (EVF)
- Women in fertile conditions can only be included with a negative pregnancy test at screening and must use appropriate contraceptives during the study
Exclusion Criteria:
- Positive tests for HIV-1/2; HBsAg, hemoglobin C, hepatitis C virus, or being positive in a Treponema Pallidum test (syphilis)
- Patients who may have been exposed to West Nile virus, or Dengue virus or human T-cell lymphotrophic virus (HTLV-1) virus should be excluded, unless the patient has been tested negative
- Concurrent illness, e.g. uncontrolled epilepsy, cardiovascular-, cerebrovascular-, and/or respiratory disease which can worsen or cause complications in connection with blood donation
- Clinically significant autoimmune disorders or conditions of immune suppression
- Hemoglobin count ≤ 7.5mmol/l (men & women)
- Lymphocyte-numbers below 0.5 x 109/l
- Body weight below 40 kg (men) and 50 kg (women)
- Clinically abnormal ECG as judged by the Investigator
- Pregnant or breast feeding women
- Inclusion in other clinical studies 4 weeks prior to inclusion in the study
- 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
- Treatment with any immunotherapy, cytotoxic therapy or, biologic therapy 4 weeks prior to enrolment in this study
- Patients that either may be put at risk due to the blood donation or where it is not expected that an ALECSAT product of good quality can be produced, as judged by the Investigator
- Patients with uncontrolled serious bacterial, viral, fungal or parasitic infection
- Blood transfusions within 48 hours prior to donation of blood for ALECSAT production
- Known or suspected intolerance to Avastin, Irinotecan or any of the excipients as well as intolerance to recombinant humanized antibodies Performance status ≥ 3
Sites / Locations
- Aalborg Universityhospital, Department of Oncology
- Aarhus University Hospital, Department of Oncology
- Odense University Hospital, Department of Oncology
- Department of Oncology, Rigshospitalet
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Alecsat
bevacizumab/irinotecan
Arm Description
The experimental product is an autologous product based on the individual patients blood. Blood donation are performed in study weeks 0, 6, 11, 23 and 43. The patient receives treatment as bolus injection at study weeks 4, 9, 14, 26 and 46.
Patients allocated to the comparator arm will be treated in accordance with standard practice in Denmark for relapsed glioblastoma multiforme, up to 16 treatment cycles with 4 weeks duration
Outcomes
Primary Outcome Measures
Progression-free survival (PFS)
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 Bevacizumab/Irinotecan. Progression of disease is defined according to the response evaluation criteria for solid tumours (RANO)
Secondary Outcome Measures
Overall survival (OS)
To evaluate the overall survival (OS) during the study period in patients treated with ALECSAT compared to patients treated with Bevacizumab/Irinotecan by Kaplan-Meier methodology
Time to progression (TTP)
To evaluate time to progression in the two treatment groups To compare PFS in the two treatment groups by Kaplan-Meier methodology upon study completion To compare PFS in a landmark analysis in the two treatment groups after a duration of 6 and 12 months after initiation of treatment
Quality of Life by European Organization for Research and Treatment of Cancer (EORTC) questionnaire
To investigate QoL and performance status during the study period for patients treated with ALECSAT compared to patients treated with Avastin/Irinotecan
Overall Response Rate (ORR)
To compare Objective Response Rate (ORR)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02060955
Brief Title
Randomized Phase 2 Study to Investigate Efficacy of ALECSAT in Patients With GBM Measured Compared to Avastin/Irinotecan
Official Title
An Open-labelled, Randomized Phase II Study to Investigate Efficacy of Autologous Lymphoid Effector Cells Specific Against Tumour-Cells (ALECSAT) in Patients With GBM Measured as Progression Free Survival Compared to Avastin/Irinotecan
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
Substantial design modifications required.
Study Start Date
February 2014 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CytoVac A/S
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The overall purpose of the study is to investigate the efficacy and safety of ALECSAT in patients with relapse of GlioBlastoma Multiforme (GBM) after first line treatments (followed by reoperation if possible). The efficacy and safety of ALECSAT treatment is, compared to standard Bevacizumab/Irinotecan second line treatments for these patients.
Detailed Description
This study is an open-label, randomized, prospective, parallel group phase II study with ALECSAT compared to Bevacizumab/Irinotecan in patients with verified relapsed glioblastoma multiforme after or during treatment with recognised first-line treatment. After 62 PFS events have been recorded, an interim analysis will be conducted under the auspices of the Data Monitoring Committee.
The patients in the two treatment groups will be followed for up to 62 weeks by planned study visits. Patients with, at least, stable disease will continue the allocated treatment after the study period as judged by the Investigator. Patients allocated to the Bevacizumab/Irinotecan (control group) will receive their treatment according to standard praxis, i.e. up to 16 treatment cycles with 4 weeks duration. Each cycle of Bevacizumab/Irinotecan consist of 2 dosing days; day 1 and day 15 in the cycle.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme
Keywords
Glioblastoma multiforme, Immunotherapy, Bevacizumab/Irinotecan, ALECSAT, recurrent
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Alecsat
Arm Type
Experimental
Arm Description
The experimental product is an autologous product based on the individual patients blood. Blood donation are performed in study weeks 0, 6, 11, 23 and 43.
The patient receives treatment as bolus injection at study weeks 4, 9, 14, 26 and 46.
Arm Title
bevacizumab/irinotecan
Arm Type
Active Comparator
Arm Description
Patients allocated to the comparator arm will be treated in accordance with standard practice in Denmark for relapsed glioblastoma multiforme, up to 16 treatment cycles with 4 weeks duration
Intervention Type
Biological
Intervention Name(s)
ALECSAT
Other Intervention Name(s)
ALECSAT, the investigational product,
Intervention Description
The ALECSAT will be administered at week 4, 9, 14, 26 and week 46. Cells are re-suspended in a plasmalyte injection fluid up to a total volume of 20 ml. The 20 ml cell suspension will contain between 10 million and 1 billion cells. Each dose is supplied in a sterile 20 ml syringe and should be injected intravenously.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab/Irinotecan
Other Intervention Name(s)
Bevacizumab, Irinotecan
Intervention Description
Patients allocated to the Bevacizumab/Irinotecan (control group) will receive treatment according to standard praxis, i.e. up to 16 treatment cycles with 4 weeks duration. Each cycle consist of 2 dosing days; day 1 and day 15 in the cycle.
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
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 Bevacizumab/Irinotecan. Progression of disease is defined according to the response evaluation criteria for solid tumours (RANO)
Time Frame
During the study period up to 62 weeks
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
To evaluate the overall survival (OS) during the study period in patients treated with ALECSAT compared to patients treated with Bevacizumab/Irinotecan by Kaplan-Meier methodology
Time Frame
During the study period up to 62 weeks
Title
Time to progression (TTP)
Description
To evaluate time to progression in the two treatment groups To compare PFS in the two treatment groups by Kaplan-Meier methodology upon study completion To compare PFS in a landmark analysis in the two treatment groups after a duration of 6 and 12 months after initiation of treatment
Time Frame
During the study period up to 62 weeks
Title
Quality of Life by European Organization for Research and Treatment of Cancer (EORTC) questionnaire
Description
To investigate QoL and performance status during the study period for patients treated with ALECSAT compared to patients treated with Avastin/Irinotecan
Time Frame
During the study period up to 62 weeks
Title
Overall Response Rate (ORR)
Description
To compare Objective Response Rate (ORR)
Time Frame
During the study period up to 62 weeks
Other Pre-specified Outcome Measures:
Title
Safety & tolerability
Description
Comparison of type and frequency of AEs; changes in biochemical parameters of clinical relevance; in hematology parameters of clinical relevance; in vital signs and change in electrocardiogram (ECG). Evaluation of medical events of special interest.
Time Frame
During the study period up to 62 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed GBM tumour with recurrence during or after completing the recognized first-line treatments, tumor recurrence, documented by MRI,
Minimum age of 18 years old,
Capable of understanding the information and giving informed consent
Minimum height of 155 cm
Expected survival time (life expectancy) of over 3 months
Adequate performance status equal or below 2
Clinically normal Erythrocyte Volume Fraction (EVF)
Women in fertile conditions can only be included with a negative pregnancy test at screening and must use appropriate contraceptives during the study
Exclusion Criteria:
Positive tests for HIV-1/2; HBsAg, hemoglobin C, hepatitis C virus, or being positive in a Treponema Pallidum test (syphilis)
Patients who may have been exposed to West Nile virus, or Dengue virus or human T-cell lymphotrophic virus (HTLV-1) virus should be excluded, unless the patient has been tested negative
Concurrent illness, e.g. uncontrolled epilepsy, cardiovascular-, cerebrovascular-, and/or respiratory disease which can worsen or cause complications in connection with blood donation
Clinically significant autoimmune disorders or conditions of immune suppression
Hemoglobin count ≤ 7.5mmol/l (men & women)
Lymphocyte-numbers below 0.5 x 109/l
Body weight below 40 kg (men) and 50 kg (women)
Clinically abnormal ECG as judged by the Investigator
Pregnant or breast feeding women
Inclusion in other clinical studies 4 weeks prior to inclusion in the study
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
Treatment with any immunotherapy, cytotoxic therapy or, biologic therapy 4 weeks prior to enrolment in this study
Patients that either may be put at risk due to the blood donation or where it is not expected that an ALECSAT product of good quality can be produced, as judged by the Investigator
Patients with uncontrolled serious bacterial, viral, fungal or parasitic infection
Blood transfusions within 48 hours prior to donation of blood for ALECSAT production
Known or suspected intolerance to Avastin, Irinotecan or any of the excipients as well as intolerance to recombinant humanized antibodies Performance status ≥ 3
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Roland Jensen, PhD
Organizational Affiliation
CytoVac A/S (Sponsor)
Official's Role
Study Director
Facility Information:
Facility Name
Aalborg Universityhospital, Department of Oncology
City
Aalborg
State/Province
Hobrovej 18-22
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Aarhus University Hospital, Department of Oncology
City
Aarhus
State/Province
Nørrebrogade 44
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Odense University Hospital, Department of Oncology
City
Odense
State/Province
Sdr. Boulevard 29
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Department of Oncology, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
DK-2100
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Randomized Phase 2 Study to Investigate Efficacy of ALECSAT in Patients With GBM Measured Compared to Avastin/Irinotecan
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