Randomized Phase 2 Study to Investigate Efficacy of ALECSAT in Patients With GBM Measured Compared to Avastin/Irinotecan

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

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.

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.

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