Open Label Randomized Phase II/III Trial of Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy (DEN-STEM)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
Open, randomized study of a trivalent dendritic cell therapy compared to standard therapy in primary treated patients with IDH wild-type, MGMT-promotor methylated glioblastoma. The IMP is dendritic cells transfected with mRNA of survivin, hTERT og autologous tumor stem cells derived from tumorspheres.
详细描述
Autologous leukapheresis for enrichment of PBMCs is performed after enrollment of the patient into the trial. Ex vivo generated DCs will be frozen and stored in the vapour phase of liquid nitrogen.
At first surgery, tumor biopsies will be cultured under sphere-forming conditions under ex vivo conditions for enrichment of glioblastoma stem cells. mRNA will purified and amplified from these autologous tumor stem cells.
At specified intervals patients randomized to the vaccine group will receive intradermal injections of DCs transfected with mRNA from autologous tumor stem cells, survivin and hTERT. Injections will be given as three separate injections at three separate sites.
Vaccination will be continued for as long as there are vaccines available.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All of the following conditions must apply:
- •Must be at least 18 years and less than 70 years of age.
- •Must be ambulatory with a ECOG performance status 0 or 1
- •Must have histologically confirmed glioblastoma IDH wild-type, with unmethylated MGMT-gene promotor, and a candidate for combined radiation therapy and chemotherapy ("Stupps Regimen").
- •Must have accessible volume and quality of tumor tissue for vaccine production (proliferation of cells and extraction of tumor mRNA) at first surgery.
- •Must have postoperative MRI after surgery with contrast enhancing tumor remnant of less than 1 cm3 or less than 10% of original tumor volume.
- •Normal organ function defined by laboratory values as following: ANC > 1.5 x 109/L; platelets >100 x109/L, Hb >9g/dL (> 5.6 mmol/L). Creatinine < 140 µmol/L (1.6 mg/dL); if borderline, the creatinine clearance >40 mL/min, Bilirubin < 20% above the upper limit of normal, ASAT and ALAT < 2.5 the upper limit of normal. Albumin >2.5 g/L.
- •Serology indicating contagious HIV, HBV, HCV and Treponema pallidum must be negative.
- •Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
排除标准
- •Tumor in a localization where a modest increase in size due to reactive oedema may have a large impact on the patient's neurological condition, i.e. brain stem.
- •History of prior malignancy other than glioblastoma, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin and ca. cervicis stage IB.
- •Active infection requiring antibiotic therapy.
- •Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia.
- •Prior splenectomy.
- •Glucocorticoid treatment not possible to terminate due to autoimmune disease or increased intracranial pressure.
- •Adverse reactions to vaccines such as asthma, anaphylaxis or other serious reactions.
- •History of immunodeficiency or autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis-dermatomyositis, juvenile onset insulin dependent diabetes, or a vasculitic syndrome.
- •Chemotherapy or other potentially immune-suppressive therapy outside protocol that has been administered within the last 4 weeks prior to vaccination.
- •Positive pregnancy test in women of childbearing potential (within 7 days before the first vaccination). Women of childbearing potential and sexually active male participants must use reliable methods of contraception during the whole treatment period and 3 months after the last trial drug dose. Reliable methods of contraception are defined in section .
- •Any reason why, in the opinion of the investigator, the patient should not participate.
研究组 & 干预措施
DC immunization
Leukapheresis before start of radiotherapy. Immunization with DCs starting first week after finalizing radiotherapy (2Gy x 30) and concomitant temozolomide.
干预措施: Dendritic cell immunization (Biological)
Standard therapy
Radiotherapy (2 Gy x30) with concomitant and adjuvant temozolomide.
干预措施: Adjuvant temozolomide (Drug)
结局指标
主要结局
Progression free survival
时间窗: 2 years
Defined as time from first surgery to first certain progress of contrast enhancing tumor or clinical progression, according to the Response Assessment in Neuro-Oncology (RANO) criteria.
次要结局
- Overall survival(2 years from inclusion)
- Patient reported quality of life, overall(2 years from inclusion)
- Patient reported quality of life, brain specific(2 years from inclusion)
- Immunological response, skin(2 years from inclusion)
- Immunological response, cellular(2 years from inclusion)
- Adverse events(2 years from inclusion)
研究者
Einar Vik-Mo
Senior consultant
Oslo University Hospital