Phase I/II Study of Intradermal IMA950 Peptide-based Vaccine Adjuvanted With Intra Muscular Poly-ICLC in Combination With Temozolomide in Newly Diagnosed HLA-A2 Glioblastoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0
研究概览
简要总结
RATIONALE : IMA 950 is multi tumour-associated peptides (TUMAPs) vaccine, these peptides have been identified on primary glioblastoma multiforme (GBM) cells. Poly-ICLC is a potent vaccine adjuvant with broad innate and adaptive immune enhancing effects. IMA 950 and Poly-ICLC will be administered to patients alongside standard primary therapy for glioblastoma. This includes the alkylating drug temozolomide (TMZ). Effective vaccine-induced immune responses associated with prolonged survival have been observed in glioblastoma patients during TMZ adjuvant therapy, suggesting a possible synergistic effect. A second component of glioblastoma standard treatment is external beam irradiation of the tumor site post-surgery. As a side effect, potentially beneficial tumor-infiltrating immune cells may also be killed by radiation. However, the combination of radiation with immunotherapy has been suggested to be favorable both in pre-clinical models.
详细描述
OBJECTIVES
Primary
- Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0.
- Immunogenicity of IMA950 plus Poly-ICLC when given together with temozolomide.
Secondary
- 6, 9 month progression free survival (PFS) using gadolinium enhanced MRI and clinical assessment according to revised RANO criteria
- Overall survival (OS)
- Immunologic endpoints (correlation between clinical and immunological responses):
- evaluation of peptide immunogenicity by tetramer staining
- analysis of memory, activation and homing marker expression by tetramer positive cells
- analysis of cytokine secretion and proliferation by antigen-specific CD4 and CD8 T cells
- analysis of the presence of T regulatory and myeloid-derived suppressor cells
- The immunological analyses will be performed on:
- peripheral blood mononuclear cells (PBMC)
- cultures of skin punch biopsy at delayed-type hypersensitivity (DTH) site
- tumor-infiltrating lymphocytes (TIL) if brain tissue is available at recurrence
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
- •Histological documentation of glioblastoma. For experimental purposes only, 5 additional grade III astrocytoma may be included (these cases will not be included in the endpoints analysis).
- •Patients must have completed radiation therapy with concomitant temozolomide.
- •HLA-A2 positive.
- •Eastern Cooperative Oncology Group performance status of 0 or 1 (Appendix1).
- •Age > 18 years, life expectancy of least 4 months.
- •Patient must be on stable or decreasing dose of steroids, with a maximal dose of Dexamethasone of 4mg/day.
- •Adequate bone marrow, liver and kidney function.
- •Hepatitis B serology negative (HBcAg-seronegative)
- •Written (signed and dated) informed consent. Capable of co-operating with standard therapy and IMA950 with Poly-ICLC vaccinations and follow-up.
排除标准
- •Any other vaccination given within 2 weeks before first IMA950 vaccination.
- •History of cardiac disease: congestive heart failure > New York heart association class 2, active CAD, cardiac requiring anti-arrhythmic therapy or uncontrolled hypertension.
- •History of HIV infection or chronic hepatitis B or C or clinical active infections.
- •Patients with evidence of history bleeding diathesis.
- •Pregnant or potentially pregnant patients. Women of childbearing age must be tested for pregnancy (serum or urine HCG) before treatment and must not contemplate pregnancy during the study
研究组 & 干预措施
IMA 950 and Poly ICLC
干预措施: IMA 950 (Biological)
IMA 950 and Poly ICLC
干预措施: Immunomonitoring (Other)
IMA 950 and Poly ICLC
干预措施: Poly ICLC (Biological)
结局指标
主要结局
Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0
时间窗: up to 2 years
次要结局
- 6, 9 month progression free survival (PFS) using gadolinium enhanced MRI and clinical assessment according to revised RANO criteria(up to 2 years)
- Overall survival (OS)(up to 2 years)
- Immunologic endpoints(up to 2 years)
研究者
Pierre-Yves Dietrich
Professor
University Hospital, Geneva