First-line immunotherapy using Wilms’ tumor protein 1 (WT1)-targeted dendritic cell vaccinations for malignant pleural mesothelioma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Safety will be assessed by clinical laboratory tests and adverse event reporting: (1) Microbiological testing (bacteria, fungi, mycoplasma, endotoxin) will be performed to assess safe DC vaccine production, (2) Local toxicity (e.g. skin reactions at injection site) will be reported, (3) Systemic toxicity will be scored according to the latest version of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC)
研究概览
简要总结
To evaluate the feasibility and safety of Wilms' tumor 1 mRNA-electroporated dendritic cell (DC) vaccinations in patients with malignant pleural mesothelioma (MPM) as first-line treatment combined with standard chemotherapy
详细描述
Malignant pleural mesothelioma (MPM) is a highly aggressive and in virtually all cases fatal cancer that is tightly associated with prior asbestos exposure. Despite some improvement over time, the prognosis of patient diagnosed with MPM remains dismal with a median overall survival from diagnosis of only 12 months.
In this single arm phase I/II trial the investigators want to demonstrate the feasibility and safety of WT1-targeted dendritic cell vaccination in MPM patients as frontline treatment in conjunction with first line platinum/pemetrexed-based chemotherapy and the induction of both systemic and in situ mesothelioma-specific immune responses. During three years of recruitment the investigators aim at including 20 patients diagnosed with histologically proven epithelial MPM (WHO grade 0-1) who are able to undergo leukapheresis, chemotherapy, immunotherapy and pleurectomy/decortication (P/D; in case of resectable disease). Patients who underwent prior treatment for MPM or with a history of another malignancy within the last five years will be excluded.
The intention of this study is to administer four vaccine doses in combination with standard of care of four 3-weekly cytoreductive platinum/pemetrexed-based chemotherapy cycles to each participant and prior to surgery (P/D) in the case of resectable MPM. Patients will receive four 3-weekly intradermal vaccinations with autologous WT1 messenger (m)RNA-loaded dendritic cells (V1-4), at day 14 after the start of each chemotherapy cycle (CT1-4).
The dendritic cell therapy product will be generated and administered in the Antwerp University Hospital, more specifically the Center for Cell Therapy and Regenerative Medicine (CCRG) and the Division of Hematology, both headed by Prof. Zwi Berneman.
The DC vaccines will be under embargo from release until the safety and quality control test results have become available and all release criteria have been met. A detailed overview of all applicable release criteria is provided in the investigational medicinal product dossier. The embargo period generally lasts 3 weeks counting from the day of cryopreservation (i.e. 8 days after leukapheresis).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Diagnosis with histologically proven epithelial MPM
- •Age: ≥18 years at the time of enrollment
- •WHO performance status 0–1 at the time of enrollment
- •Fit to undergo general anesthesia, a thoracoscopy, leukapheresis, chemotherapy, immunotherapy and (in case of resectable disease) P/D
- •No history of receiving any investigational treatment within 28 days of study enrollment
- •No history of intolerance to pemetrexed and/or cisplatin
- •Before patient registration written informed consent must be given according to ICH/GCP, and national/local regulations
排除标准
- •Unwilling or unable to comply with the study requirements
- •Prior treatment for mesothelioma
- •History of other malignancy within the last five years, except for non-melanoma skin cancer and cervical carcinoma in situ or unless the investigator rationalizes otherwise
- •Known proven metastases
- •Known concomitant presence of any immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo
- •Pregnant or breastfeeding
结局指标
主要结局
Safety will be assessed by clinical laboratory tests and adverse event reporting: (1) Microbiological testing (bacteria, fungi, mycoplasma, endotoxin) will be performed to assess safe DC vaccine production, (2) Local toxicity (e.g. skin reactions at injection site) will be reported, (3) Systemic toxicity will be scored according to the latest version of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC)
Safety will be assessed by clinical laboratory tests and adverse event reporting: (1) Microbiological testing (bacteria, fungi, mycoplasma, endotoxin) will be performed to assess safe DC vaccine production, (2) Local toxicity (e.g. skin reactions at injection site) will be reported, (3) Systemic toxicity will be scored according to the latest version of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC)
Feasibility will be assessed based on the success of (1) leukapheresis and (2) DC vaccine preparation (production of at least 4 DC vaccines) and (3) administration of combined chemoimmunotherapy cycles within the proposed time schedule
Feasibility will be assessed based on the success of (1) leukapheresis and (2) DC vaccine preparation (production of at least 4 DC vaccines) and (3) administration of combined chemoimmunotherapy cycles within the proposed time schedule
次要结局
- Clinical endpoints: time to progression (TTP), progression-free survival (PFS) and overal survival (OS) (Tumor assessment will be performed according to the latest modified Response Evaluation Criteria In Solid Tumors (RECIST), PET Response Criteria In Solid Tumors (PERCIST) and endpoints for cancer immunotherapy trials)
- Translational endpoint: immunological responses (Systemic and local immunological response analysis will be performed to determine the in vivo immunogenicity of WT1 mRNA-electroporated DC vaccinations when combined with chemotherapy for the frontline treatment of MPM by evaluating the development of effective anti-mesothelioma immunity)
研究者
Center for Cell Therapy and Regenerative Medicine
Scientific
Antwerp University Hospital