Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate in Glioblastoma: a Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- clinical activity
研究概览
简要总结
Single arm, monocentric trial to assess the safety and the progression-free survival related to the combined treatment of dendritic cell vaccine loaded with autologous tumor homogenate and temozolomide in patients operated for glioblastoma and then treated with standard radiochemotherapy (according to Stupp regimen).
详细描述
Single arm, monocentric trial to assess the safety and the progression-free survival related to the combined treatment of dendritic cell vaccine loaded with autologous tumor homogenate and temozolomide in patients operated for glioblastoma and then treated with standard radiochemotherapy (according to Stupp regimen).
The experimental treatment consists of an induction phase with 4 weekly doses of dendritic cell vaccine (10x10exp6 cells) intradermally administered (weeks 1-4), followed by a maintenance phase consisting of 28 days cycles with vaccine administration (start on week 7) and adjuvant temozolomide (150-200mg/m2/day) assumed orally from day 1 to 5 q28 (start on week 5). The combined maintenance treatment will continue until disease progression, unacceptable toxicity or withdrawal of consent by the patient, or up to a maximum of 1 year of treatments. After disease progression or the end of maintenance phase, is foreseen a one-year follow-up phase for each subject.
Primary objectives are clinical activity and safety of the study treatment. Secondary objectives are the evaluation of the prognostic role of the positive Delayed-Type Hypersensitivity (DTH) skin test after at least four vaccine administrations, the OS and the immunological efficacy of the study treatment. A series of exploratory objectives will be also assessed on samples from patients who participate to this optional part of the trial.
Simon's two-stage design (Simon, 1989) will be used for the sample size calculation.
A planned interim analysis will be done after the recruitment of the first 9 evaluable patients for toxicity and for efficacy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed "monofocal" glioblastoma
- •THE AUTOLOGOUS SURGICAL SPECIMEN NEEDED FOR VACCINE MANUFACTURING MUST HAVE BEEN COLLECTED AND SENT TO THE SOMATIC CELL THERAPY LAB OF ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI (IRST) ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO (IRCCS) AND MUST FULFIL ALL THE ACCEPTANCE CRITERIA PRESCRIBED BY THE GOOD MANUFACTURING PRACTICES (GMP) PROCEDURES.
- •Availability of sufficient leukapheretic material for the preparation of the vaccine product.
- •No progressive disease near-complete resection (= 5 ml residual tumor volume) confirmed by MRI after standard radiochemotherapy treatment (Stupp regimen)
- •Patients must have recovered (grade 1 or less by CTCAE 5.0) from all the events related to previous treatments.
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be >= 18 years of age on day of signing informed consent.
- •Have a Karnofsky performance status (KPS) = 70% or a performance status of 0 or 1 on the ECOG Performance Scale.
- •Demonstrate adequate organ and marrow function
排除标准
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 10 mg prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Has a known history of active Bacillus Tuberculosis (TB)
- •Previous treatment with a cancer vaccine
- •Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years, except basal or squamous cell carcinoma of the skin and in situ carcinoma of the cervix uteri treated with radical surgery.
- •Any known history of or is positivity of any serologic marker indicative of infection by Treponema pallidum, hepatitis B virus (HBsAg, HBsAb, HBcAB), hepatitis C virus (HCVAb, HCV RNA quantitative), human immunodeficiency virus (HIV), whether actual or previous.
- •Has received a live vaccine within 30 days of planned start of study therapy.
研究组 & 干预措施
Experimental treatment
Induction phase: 4 weekly doses of dendritic cell vaccine (10x10exp6 cells) intradermally administered (weeks 1-4).
Maintenance phase: 28 days cycles with vaccine administration (start on week 7) and adjuvant temozolomide (150-200mg/m2/day) assumed orally from day 1 to 5 q28 (start on week 5). The combined maintenance treatment will continue until disease progression, unacceptable toxicity or withdrawal of consent by the patient, or up to a maximum of 1 year of treatments.
After disease progression or the end of maintenance phase, is foreseen a one-year follow-up phase for each subject.
干预措施: Autologous Dendritic Cells (DC) vaccine (Biological)
Experimental treatment
Induction phase: 4 weekly doses of dendritic cell vaccine (10x10exp6 cells) intradermally administered (weeks 1-4).
Maintenance phase: 28 days cycles with vaccine administration (start on week 7) and adjuvant temozolomide (150-200mg/m2/day) assumed orally from day 1 to 5 q28 (start on week 5). The combined maintenance treatment will continue until disease progression, unacceptable toxicity or withdrawal of consent by the patient, or up to a maximum of 1 year of treatments.
After disease progression or the end of maintenance phase, is foreseen a one-year follow-up phase for each subject.
干预措施: Temozolomide (Drug)
结局指标
主要结局
clinical activity
时间窗: about 55 months
Progression free survival (PFS), measured as the proportion of patients without progression of disease at three months from leukapheresis
Incidence of Treatment-Emergent Adverse Events
时间窗: about 55 months
Proportion of patients experienced grade 3 or higher adverse events related to the study treatment
次要结局
- Immune response in vivo(about 32 months)
- Clinical Outcome (Overall Survival (OS))(about 55 months)
- Immunological efficacy(about 55 months)
- Human leukocyte antigen (HLA) class I and II characterization characterization of patients(about 32 months)