A Phase I Study Of Active Immunotherapy With Autologous Dendritic Cells Infected With CEA-6D Expressing Fowlpox -Tricom In Patients With Advanced Or Metastatic Malignancies Expressing CEA
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Safety
研究概览
简要总结
RATIONALE: Vaccines made from a person's white blood cells that have been treated in the laboratory may make the body build an immune response to kill tumor cells.
PURPOSE: Phase I trial to study the effectiveness of vaccine therapy in treating patients who have advanced or metastatic cancer.
详细描述
OBJECTIVES:
- Determine the safety and feasibility of active immunotherapy comprising autologous dendritic cells infected with recombinant fowlpox-CEA-TRICOM vaccine in patients with advanced or metastatic malignancies expressing CEA.
- Assess the CEA-specific immune response of patients treated with this regimen.
- Assess, in a preliminary manner, the clinical response rate of patients treated with this regimen.
OUTLINE: This is a dose-escalation study.
Autologous dendritic cells (ADCs) are harvested and infected with fowlpox-CEA-TRICOM vaccine. Patients receive the infected ADCs intradermally and subcutaneously (SC) followed by ADCs mixed with CMV pp65 peptide and ADCs mixed with tetanus toxoid SC and intradermally on day 1. Treatment repeats every 3 weeks for a total of 4, 8, or 12 immunizations in the absence of unacceptable toxicity.
Cohorts of 6 patients receive an escalating number of immunizations until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed advanced or metastatic malignancy expressing CEA
- •Metastatic disease meeting one of the following criteria:
- •Measurable or nonmeasurable
- •History of metastases but no current evidence of disease, meeting one of the following criteria:
- •Unresectable peritoneal or lymph node metastases that cannot be detected by imaging
- •Treated or resected metastatic disease considered at high risk of recurrence (predicted 5-year disease-free survival of less than 50%)
- •Must have completed treatment that rendered no evidence of disease within the past year
- •CEA-expressing malignancy is defined by any of the following:
- •Immunohistochemical staining (at least 50% of the tumor has at least a moderate intensity of staining)
- •CEA level in peripheral blood greater than 2.5 µg/L
- •Tumor known to be universally CEA positive (e.g., colon and rectal cancer)
- •Received prior therapy with possible survival benefit or refused such therapy
- •Prior resection of brain metastases allowed provided no metastasis by CT scan or MRI of the brain within 1 month of enrollment
- •Hormone receptor status:
- •Not specified
- •PATIENT CHARACTERISTICS:
- •18 and over Sex
- •Male or female Menopausal status
- •Not specified Performance status
- •Karnofsky 70-100% Life expectancy
- •More than 6 months
- •Hematopoietic
- •WBC at least 3,000/mm^3
- •Absolute lymphocyte count at least 1,000/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 9 g/dL (transfusion or epoetin alfa allowed) Hepatic
- •Bilirubin less than 2.0 mg/dL
- •SGOT/SGPT less than 1.5 times upper limit of normal
- •No active acute or chronic viral hepatitis
- •Hepatitis B surface antigen negative
- •Hepatitis C negative
- •No other hepatic disease that would preclude study entry
- •Creatinine less than 2.5 mg/dL
- •No active acute or chronic urinary tract infection
- •Cardiovascular
- •No New York Heart Association class III or IV heart disease Immunologic
- •HIV negative
- •No history of autoimmune disease, including, but not limited to, the following:
- •Inflammatory bowel disease
- •Systemic lupus erythematosus
- •Rheumatoid arthritis
- •Ankylosing spondylitis
- •Scleroderma
- •Multiple sclerosis
- •No allergy to eggs or any component of study vaccine Other
- •No active acute or chronic infection
- •No concurrent serious acute or chronic illness that would preclude study entry
- •No other medical or psychological impediment that would preclude study entry
- •No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled carcinoma in situ of the cervix, or controlled superficial bladder cancer
- 另有 21 项未显示
排除标准
- 未提供
研究组 & 干预措施
TRICOM-CEA(6D)
Subjects receiving TRICOM-CEA(6D)
干预措施: TRICOM-CEA(6D) (Biological)
结局指标
主要结局
Safety
时间窗: 12-36 weeks
The primary objective of this protocol is to determine the safety and feasibility of rF-CEA(6D)-TRICOM loaded DC in, subjects with metastatic, CEA expressing malignancies.
次要结局
- Immune response(12-36 weeks)
研究者
Michael Morse, MD
Principal Investigator
Duke University