NY-ESO-1 Protein Vaccination in Malignant Melanoma Administered With Imiquimod as Adjuvant
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Number of Patients With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This was a Phase 1, single-arm, open-label, pilot study of NY-ESO-1 protein vaccination with imiquimod as an adjuvant in patients with resected Stage IIB, IIC, and III malignant melanoma. The primary study objective was to determine the safety of NY-ESO-1 protein/imiquimod treatment, and the secondary objective was to evaluate the immunogenicity of treatment.
详细描述
Patients applied imiquimod (250 mg) topically to a designated area of healthy skin on the upper inner arm or inner thigh (the cream remained on the skin overnight for 6-10 hours) every day for 5 consecutive days (i.e., for the first 5 days of Cycles 1-3 and for the first 4 days of Cycle 4). The NY-ESO-1 protein (100 μg) was injected intradermally into the imiquimod-pretreated area on Day 3 of each cycle for 4 consecutive 21-day cycles.
Safety was monitored continuously. Immunization was assessed by the generation of NY-ESO-1-specific cluster of differentiation (CD)4+ and CD8+ T cell responses in enzyme-linked immunosorbent spot (ELISPOT) assays and by the development or augmentation of NY-ESO-1-specific antibody titers, assessed by enzyme-linked immunosorbent assay (ELISA).
Blood samples were obtained for the assessment of clinical biochemistry and hematology, and physical examinations were performed at baseline, on Day 1 of each cycle, and at a follow-up visit at Week 13.
Skin biopsies of the vaccinated area were obtained 48 hours after the last injection (Day 5 of Cycle 4). To avoid irritation, imiquimod was not applied after the biopsies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Had histologically confirmed, resected American Joint Committee on Cancer Stage IIB, IIC or III malignant melanoma
- •Fully recovered from surgery
- •Age ≥ 18 years; children were excluded from this study, as the safety of imiquimod had not been established in patients below the age of 18
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Adequate organ and marrow function as defined below:
- •absolute neutrophil count: ≥ 1500/μL
- •hemoglobin: ≥ 9 g/dL
- •platelets: ≥ 100,000/μL
- •total bilirubin: ≤ 1.5 × institutional upper limit of normal (ULN)
- •aspartate aminotransferase/alanine aminotransferase (AST/ALT): ≤ 2.5 × institutional ULN
- •creatinine: ≤ 1.5 × institutional ULN
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Received chemotherapy, immunotherapy (including interferon), or radiotherapy within 4 weeks prior to first dosing of study agent
- •Prior treatment with NY-ESO-1 vaccines
- •Known human immunodeficiency virus infection or autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions could have interfered with the evaluation of the induced immune response; patients with vitiligo or melanoma-associated hypopigmentation were not excluded
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to imiquimod or other agents used in the study
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would have limited compliance with study requirements
- •Pregnancy or lactation
- •Women of childbearing potential not using a medically acceptable means of contraception
- •Known history of inflammatory skin disorders, as imiquimod might have exacerbated these conditions
- •Chronic corticosteroid or immunosuppressive therapies, as these might have interfered with the evaluation of the induced immune response
- •Lack of availability for immunological and clinical follow-up assessments
研究组 & 干预措施
Imiquimod + NY-ESO-1
Patients applied topical imiquimod followed by vaccination with intradermal injections of the NY-ESO-1 protein.
干预措施: Imiquimod (Drug)
Imiquimod + NY-ESO-1
Patients applied topical imiquimod followed by vaccination with intradermal injections of the NY-ESO-1 protein.
干预措施: NY-ESO-1 protein (Biological)
结局指标
主要结局
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 4 months
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the time informed consent was signed through the last follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
次要结局
- Number of Patients With Cellular Antibody Response to NY-ESO-1 at Two or More Post-vaccination Time Points(Up to 4 months)
- Number of Patients With Humoral Antibody Response to NY-ESO-1(Up to 4 months)