Efficacy & Safety of Autologous Dendritic Cell Vaccination in Glioblastoma Multiforme After Complete Surgical Resection
Prospective, Phase II Clinical Trial to Evaluate Efficacy and Safety of Autologous Dendritic Cell Vaccination in Glioblastoma Multiforme Patients After Complete Surgical Resection With Fluorescence Microscope
Primary outcome measure:
a.Evaluation of the treatment impact on progression-free survival.
Secondary outcome measures:
Safety evaluation.
- Direct effects attributable cell obtaining and administration.
- Adverse events during treatment.
- Neurological deterioration quantified using the NIH Stroke Scale.
- Autoimmune phenomena.
Evaluation of impact on other efficiency clinical parameters.
- Overall survival.
- Quality of life measured with EORTC questionnaire.
Study of specific immune response and correlates with clinical outcome.
- Delayed hypersensitivity.
- Humoral response to autologous tumor cells/tumoral lysate.
- Cellular response (proliferation, cytokine production, specific cytotoxicity).
Cell line characterization and correlate the final product with clinical efficacy.
- Phenotypic studies.
研究概览
详细说明
A prospective, open-label, unicentric phase II trial, historical control and non-randomized.
The study will try to evaluate the efficiency and safety of the experimental treatment using a cell therapy product (tumor lysate-pulsed autologous dendritic cell vaccine) in patients with glioblastoma multiforme in whom a gross total resection is feasible. Patients will receive standard first-line therapy (surgery before radio-chemotherapy) along with the experimental treatment. The experimental treatment consists in subcutaneous vaccination with a suspension of autologous dendritic cells (cells from the same patient) produced by cell culture from monocytes from the same patient extracted by leukapheresis and pulsed with a lysate of the patient´s tumoral tissue. The first four vaccines will be administered on a monthly basis, concomitantly with the standard chemo and radiotherapy treatments, the next four vaccines, every other month and the four last vaccinations every three months.The results obtained will be compared with those of an historical control study, where patients received a standard treatment without the experimental vaccine.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Pamplona、西班牙、31008
- Clinica Universidad de Navarra
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Patients with histological diagnosis of glioblastoma that have not received any previous chemotherapy or radiotherapy treatment.
- Patients are able to give informed consent and willing to comply with the protocol requirements during the study period.
- Age between 18 and 70 years
- Negative pregnancy test In female fertile subjects
- Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
- Complete/Total resection of tumour with surgery guided by fluorescence microscopy and 5-aminolevulinic acid, observed with post operative magnetic resonance imaging. The residual lesion must be null or ≤ 1 cm3 by contrast capturing.
- Enough tumor tissue available for the cellular vaccine elaboration
Exclusion Criteria:
- Patients with infections, severe diseases or hepatic, renal or medullary failures, that in the investigator's opinion, are not eligible to participate in the study.
- Participation in other clinical trial. If the patient has participated in other clinical trial within previous months, the patient has to complete the washout period required by de the investigator.
- Patients with diagnosis of other neoplasia, except basal cell or squamous cell skin, carcinoma in situ of the cervix properly treated or other tumour curatively treated and no evidence of relapse for at least 3 years. Those cases with coexisting tumours of long-term survival prediction will be considered individually.
- Pregnant or breast-feeding women.
- Patients who need immunosuppressive drugs.
- Positive serology for HIV , hepatitis B (HBsAg) or hepatitis C virus.
- Impossible to get enough material for at least 6 cellular vaccine production.
- Absolute contraindication for the patient to receive other steps of standard treatment of glioblastoma (surgery, radio and chemotherapy)
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Vaccination
Autologous Dendritic cells loaded with tumor lysate
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Patients will receive standard first-line therapy (surgery before radio-chemotherapy) along with the experimental treatment.
The experimental treatment consists in subcutaneous vaccination with a suspension of autologous dendritic cells (cells from the same patient) produced by cell culture from monocytes from the same patient extracted by leukapheresis and pulsed with a lysate of the patient´s tumoral tissue.
The first four vaccines will be administered on a monthly basis, concomitantly with the standard chemo and radiotherapy treatments, the next four vaccines, every other month and the four last vaccinations every three months.The results obtained will be compared with those of an historical control study, where patients received a standard treatment without the experimental vaccine.
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Evaluation of the treatment impact on progression-free survival
大体时间：5 years
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5 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Safety evaluation
大体时间：5 years
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5 years
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Evaluation of impact on other efficiency clinical parameters
大体时间：5 years
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5 years
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Study of specific immune response and correlates with clinical outcome
大体时间：5 years
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5 years
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Cell line characterization and correlate the final product with clinical efficacy
大体时间：5 years
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a. Phenotypic studies
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5 years
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合作者和调查者
调查人员
- 研究主任：Felipe Prosper, MD, PhD、Clinica Universidad de Navarra
出版物和有用的链接
一般刊物
- Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
- Liau LM, Black KL, Prins RM, Sykes SN, DiPatre PL, Cloughesy TF, Becker DP, Bronstein JM. Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg. 1999 Jun;90(6):1115-24. doi: 10.3171/jns.1999.90.6.1115.
- Omuro AM, Faivre S, Raymond E. Lessons learned in the development of targeted therapy for malignant gliomas. Mol Cancer Ther. 2007 Jul;6(7):1909-19. doi: 10.1158/1535-7163.MCT-07-0047.
- Inoges S, Tejada S, de Cerio AL, Gallego Perez-Larraya J, Espinos J, Idoate MA, Dominguez PD, de Eulate RG, Aristu J, Bendandi M, Pastor F, Alonso M, Andreu E, Cardoso FP, Valle RD. A phase II trial of autologous dendritic cell vaccination and radiochemotherapy following fluorescence-guided surgery in newly diagnosed glioblastoma patients. J Transl Med. 2017 May 12;15(1):104. doi: 10.1186/s12967-017-1202-z.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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