None listed
Conditions
Brief summary
Gliomas are the most common primary brain tumour in adults and children. For patients with the commonest form, glioblastoma multiforme, the median survival is approximately 1 year. Based on data from our previous trial, we hypothesize that concomitant dendritic cell vaccine therapy and celecoxib, when combined with standard postoperative radiotherapy and temozolomide, is safe and effective in patients with malignant glioma. 10 patients will receive a minimum of six vaccines, and up to 12 where possible (If recurrence or progression does not occur, vaccination will continue for up to 12 vaccinations). Dendritic cell vaccines will be manufactured from the patient’s own blood cells and tumour resected at surgery. Local radiotherapy commences approximately two weeks after surgery. This continues for five days a week, for five weeks. Throughout this period, low dose oral temozolomide is given every day. After this, a higher dose is given for five days every four weeks for six cycles. The first vaccination will be given a week before the completion of the five weeks of radiochemotherapy. Vaccinations will continue every two weeks for six treatments, and then four-six weekly thereafter. Patients will be given the oral non-steroidal anti-inflammatory drug celecoxib (400mg twice daily) over eight weeks continuously, commencing with radio-chemotherapy. Patients will be clinically evaluated at each visit, including an assessment of quality of life. Symptoms and signs of toxicity will be monitored. An MRI scan will also be done at intervals according to standard clinical protocols.
Interventions
Autologous dendritic cells pulsed with irradiated autologous tumour cells, formulated in 10% dimethyl sulfoxide, cryopreserved, and thawed just prior to injection. This product will be administered in combination with celecoxib and standard adjuvant radiochemotherapy (ie radiation and temozolomide). Local radiotherapy commences approximately two weeks after surgery. This continues for five days a week, for five weeks. Throughout this period, low dose oral temozolomide is given every day. After t
Autologous dendritic cells pulsed with irradiated autologous tumour cells, formulated in 10% dimethyl sulfoxide, cryopreserved, and thawed just prior to injection. This product will be administered in combination with celecoxib and standard adjuvant radiochemotherapy (ie radiation and temozolomide). Local radiotherapy commences approximately two weeks after surgery. This continues for five days a week, for five weeks. Throughout this period, low dose oral temozolomide is given every day. After this, a higher dose is given for five days every four weeks for six cycles. The first vaccination will be given a week before the completion of the five weeks of radiochemotherapy. Vaccinations will continue every two weeks for six treatments, and then four-six weekly thereafter. Patients will be given the oral non-steroidal anti-inflammatory drug celecoxib (400mg twice daily) over eight weeks continuously, commencing with radio-chemotherapy.
Sponsors
Queensland Institute of Medical Research
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Malignant glioma (World Health Organisation grade IV). Preoperative assessment by clinical presentation and Computed tomography (CT) / Magnetic Resonance Imaging (MRI) scans appearance of the lesion will identify suitable candidates. Progression to enrolment will be dependent upon the neuropathological diagnosis being confirmed. 2. Age 18 – 75 3. Macroscopic tumour resection (ie it was felt by the surgeon at operation that all visible tumour was resected; tumour seen on postoperative imaging does not exclude the patient from consideration) 4. Patient undergoing standard postoperative radiotherapy and concurrent temozolomide chemotherapy, followed by post-radiotherapy temozolomide.
Exclusion criteria
1. Presence of extensive intracranial or intraspinal disease which precludes total macroscopic or subtotal resection. 2. Eastern Cooperative Oncology Group (ECOG) status > 2 3. Documented history of auto-immune disease such as systemic lupus erythematosus (SLE), sarcoidosis, rheumatoid arthritis, glomerulonephritis or vasculitis. Previous use of long term immunosuppressive therapy in recent months. (NB perioperative short term dexamethasone, which is normal treatment, does not preclude inclusion in the trial) 4. Prior use of any immunotherapeutic agent. 5. Serology indicating active infection with Hepatitis B or C, human immunodeficiency virus (HIV), human T-cell leukemia virus-1 (HTLV-1) or syphilis 6. Significant non-malignant disease (eg severe cardiac or respiratory dysfunction) 7. Pregnancy 8. Presence of another malignancy. 9. Clinically relevant abnormal haematological and biochemical parameters (as assessed by the treating clinician). 10. History of significant cardiac history (ie myocardial infarction < 1year, unstable angina). 11. Severe asthma or previous reactions to any non-steroidal anti-inflammatory medication. 12. If the patient is taking regular medications known to interact with celecoxib (lithium, warfarin, other Non-steroidal anti-inflammatory drugs). 13. Inadequate venous access for leukapheresis.
Outcome results
None listed