NCT01222221已完成1 期
A Cancer Research UK Phase I Trial of IMA950 (A Novel Multi-Peptide Vaccine) Plus GM-CSF in Patients With Newly Diagnosed Glioblastoma
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 14
- 主要终点
- Causality of each adverse event (AE) to glioblastoma multiform multi-antigen vaccine IMA950 and GM-CSF and AE severity according to NCI CTCAE Version 4.0
研究概览
简要总结
RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vaccine therapy together with temozolomide and radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects of vaccine therapy when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme.
详细描述
OBJECTIVES:
Primary
- To assess the safety and tolerability of glioblastoma multiform multi-antigen vaccine IMA950 plus sargramostim (GM-CSF) in combination with standard chemoradiotherapy comprising temozolomide and radiotherapy followed by adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.
- To determine the immunogenicity of this regimen in these patients.
Secondary
- To determine the anti-tumor effect of this regimen in these patients.
- To determine the effect of pre-treatment levels of regulatory T-cells on the immunogenicity of this regimen in these patients. (Exploratory)
- To evaluate the potential effect of steroid dose on the immunological response to glioblastoma multiform multi-antigen vaccine IMA950 plus GM-CSF.
研究设计
- 研究类型
- Interventional
- 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
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed glioblastoma multiforme (astrocytoma WHO grade IV disease)
- •Newly diagnosed disease
- •Resectable tumor (not including patients undergoing biopsy only or tumors involving the brain stem or cerebellum)
- •Meets 1 of the following criteria regarding standard chemoradiotherapy:
- •Eligible for standard chemoradiotherapy with temozolomide followed by adjuvant temozolomide
- •Has undergone surgical resection before study enrollment
- •Completed standard chemoradiotherapy with temozolomide with no subsequent progression of disease
- •Expected to complete standard chemoradiotherapy and 6 courses of adjuvant temozolomide
- •HLA-A*02 positive
- •PATIENT CHARACTERISTICS:
- •WHO performance status 0-1
- •Life expectancy ≥ 30 weeks
- •Hemoglobin ≥ 9.0 g/dL
- •Absolute neutrophil count ≥ 1.5 x 10^9/L
- •Lymphocyte count ≥ 1.0 x 10^9/L (cohort 1) OR ≥ 0.35 x 10^9/L post-chemoradiotherapy and ≥ 1.0 x 10^9/L prior to the start of chemoradiotherapy (cohort 2)
- •Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT or AST ≤ 3.0 times ULN
- •Alkaline phosphatase ≤ 3.0 times ULN
- •Hepatitis B serology negative (HBcAg-seronegative)
- •No known hepatitis C or HIV serological positivity
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use one (male) or two (female) highly effective forms of contraception 2 weeks before, during, and for 6 months after completion of study therapy
- •Not at high medical risk due to nonmalignant systemic disease including active uncontrolled infection
- •No known hypersensitivity to GM-CSF or excipients
- •No history of autoimmune disease
- •No concurrent congestive heart failure
- •No prior history of NYHA class III-IV cardiac disease, cardiac ischemia, or cardiac arrhythmia
- •No other condition that might interfere with the patient's ability to generate an immune response
- •No other condition that, in the investigator's opinion, would make the patient not a good candidate for the clinical trial
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •At least 7 days since prior dexamethasone (dose > 4 mg daily or equivalent)
- •At least 4 weeks since prior major surgery for any condition (except surgical resection as part of primary standard therapy in cohort 1)
- •At least 30 days since prior and no concurrent participation in another clinical trial or planning to participate in another interventional clinical trial (concurrent participation on an observational study allowed)
- •At least 30 days since prior and no other concurrent investigational drugs
- •No prior treatment for glioblastoma including Gliadel Wafers
- •Early components of standard therapy are allowed if already initiated (i.e., surgical resection [cohort 1] or surgical resection followed by conventional external-beam radiotherapy and concomitant temozolomide [cohort 2])
- •No other concurrent anticancer therapy
- •No other concurrent vaccinations from 2 weeks before the first study vaccine to the end of the sixth study vaccine (the induction phase)
排除标准
- 未提供
结局指标
主要结局
Causality of each adverse event (AE) to glioblastoma multiform multi-antigen vaccine IMA950 and GM-CSF and AE severity according to NCI CTCAE Version 4.0
Total number of patients showing patient-individual T-cell responses against a single or multiple tumor-associated peptides (TUMAP) contained in the study vaccine IMA950 at one or more post-vaccination time points by HLA multimer analysis
次要结局
- Correlation between steroid levels and observed T-cell responses
- Correlation between O6-methyl-DNA-methyltransferase (MGMT) promoter methylation status in tumor tissue using methylation-specific polymerase chain reaction and clinical benefit (PFS at 6 months and 9 months)
- Kinetics of vaccine-induced TUMAP responses including summary descriptions of the time of onset, sustainability, and magnitude of the observed response
- Progression-free survival (PSF) at 6 and 9 months post-surgery as assessed by the Macdonald criteria from conventional gadolinium-enhanced MRI and clinical assessment
研究者
研究点 (14)
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