A Phase II Clinical Trial Evaluating Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen +/- Toll-like Receptor Agonists for the Treatment of Malignant Glioma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Most effective combination of DC vaccine components
研究概览
简要总结
The main purpose of this study is to evaluate the most effective immunotherapy vaccine components in patients with malignant glioma. Teh investigators previous phase I study (IRB #03-04-053) already confirmed that this vaccine procedure is safe in patients with malignant brain tumors, and with an indication of extended survival in several patients. However, the previous trial design did not allow us to test which formulation of the vaccine was the most effective. This phase II study will attempt to dissect out which components are most effective together. Dendritic cells (DC) (cells which "present" or "show" cell identifiers to the immune system) isolated from the subject's own blood will be treated with tumor-cell lysate isolated from tumor tissue taken from the same subject during surgery. This pulsing (combining) of antigen-presenting and tumor lysate will be done to try to stimulate the immune system to recognize and destroy the patient's intracranial brain tumor. These pulsed DCs will then be injected back into the patient intradermally as a vaccine. The investigators will also utilize adjuvant imiquimod or poly ICLC (interstitial Cajal-like cell) in some treatment cohorts. It is thought that the host immune system might be taught to "recognize" the malignant brain tumor cells as "foreign" to the body by effectively presenting unique tumor antigens to the host immune cells (T-cells) in vivo.
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
- •PATIENT ELIGIBILITY
- •Inclusion Criteria
- •Patients with newly diagnosed or recurrent glioma of WHO Grade III or IV {anaplastic astrocytoma (AA), anaplastic astro-oligodendroglioma (AO), or glioblastoma (GBM)} will be eligible for this protocol.
- •Patients must have had surgical resection at UCLA (University of California, Los Angeles), for which a separate informed consent was signed for the collection of their tumor prior to surgery.
- •After surgery, a pathological diagnosis of malignant glioma (WHO Grade III or IV) will need to be established.
- •Patients must be 18 years or older and able to read and understand the informed consent document. Patients must sign the informed consent indicating that they are aware of the investigational nature of this study.
- •Patients must have a Karnofsky performance status (KPS) rating of > 60 prior to initiating treatment. Patients may be enrolled at a KPS of < 60 if it is felt that the patient will have adequate opportunity to recover to a KPS of > 60 by the initiation of treatment.
排除标准
- •Subjects with an active infection.
- •Inability to obtain informed consent because of psychiatric or complicating medical problems.
- •Unstable or severe intercurrent medical or psychiatric conditions as determined by the Investigator.
- •Females of child-bearing potential who are pregnant or lactating or who are not using approved contraception.
- •History of immunodeficiency (e.g., HIV) or autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, vasculitis, polymyositis-dermatomyositis, scleroderma, multiple sclerosis, or juvenile-onset insulin-dependent diabetes) that may be exacerbated by immunotherapy.
- •Subjects with organ allografts.
- •Inability or unwillingness to return for required visits and follow-up exams.
- •Subjects who have an uncontrolled systemic malignancy that is not in remission.
研究组 & 干预措施
Tumor Lysate-pulsed DC vaccination
Cohort #1 will receive autologous tumor lysate-pulsed DC vaccination together with a placebo cream or intramuscular injection of saline.
干预措施: autologous tumor lysate-pulsed DC vaccination (Biological)
Tumor lysate-pulsed DC vaccination+0.2% resiquimod.
Cohort #2 will receive autologous tumor lysate-pulsed DC vaccination together with adjuvant 0.2% resiquimod.
干预措施: Tumor lysate-pulsed DC vaccination+0.2% resiquimod (Biological)
Tumor-lysate pulsed DC vaccination +adjuvant polyICLC.
Cohort #3 will receive autologous tumor lysate-pulsed DC vaccination together with adjuvant poly ICLC (TLR3 agonist).
干预措施: Tumor-lysate pulsed DC vaccination +adjuvant polyICLC (Biological)
结局指标
主要结局
Most effective combination of DC vaccine components
时间窗: 6 weeks
次要结局
- Time to tumor progression and overall survival(2 years)