Phase I/II Study of Adoptive T Cell Therapy Following In Vivo Priming With a HER-2/Neu (HER2) Intracellular Domain (ICD) Peptide-Based Vaccine in Patients With Advanced Stage HER2 Overexpressing Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Evaluate Toxicity of Infusing HER2-specific T Cells as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
研究概览
简要总结
This phase I/II trial is studying the side effects of escalating doses of adoptive T cell therapy in treating patients with stage IV breast cancer. Vaccines are given to patient prior the expansion of a person's white blood cells may help the body build an effective immune response to kill tumor cells that overexpress human epidermal growth factor receptor 2 (HER2)
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety of infusing escalating doses of HER2 specific T cells into patients with advanced HER2+ breast cancer using ex vivo expanded autologous T cells.
SECONDARY OBJECTIVES:
I. To investigate to what extent HER2 specific T cell immunity can be boosted or generated in individuals after infusion of HER2 specific T cells.
II. To evaluate how long T cell immune augmentation persists in vivo after adoptive transfer of HER2 specific T cells and subsequent booster immunizations.
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
- •Patients with HER2+ Stage IV breast cancer that have been maximally treated and not achieved a complete remission
- •Patients must have stable or slowly progressive disease state, measurable disease as:
- •Extraskeletal disease that can be accurately measured >= 10 mm by standard imaging techniques that can include but not limited to computed tomography (CT), positron emission tomography (PET), PET/CT, magnetic resonance imaging (MRI);
- •Skeletal or bone-only disease which is measurable by fludeoxyglucose (FDG) PET or PET/CT imaging will also be allowed
- •Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal therapy and/or bisphosphonate therapy
- •HER2 overexpression in the primary tumor or metastasis by immunohistochemistry (IHC) of 2+ or 3+, or documented gene amplification by fluorescence in situ hybridization (FISH) analysis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by FISH
- •Subjects must have a Performance Status Score (Southwest Oncology Group [SWOG]/Zubrod Scale) = 0, 1 or 2
- •Patients must be off all immunosuppressive treatments such as chemotherapy or systemic steroid therapy a minimum of 14 days prior to initiation of study (i.e. first vaccination)
- •Patients on trastuzumab and/or lapatinib must have a baseline left ventricular ejection fraction (LVEF) measured by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) equal to or greater than the lower limit of normal for the facility within 90 days of eligibility determination
- •Men and women of reproductive ability must agree to contraceptive use during the entire study period
- •Patients must have an expected survival of 6 months
- •White blood cell (WBC) >= 3000/mm^3
- •Absolute neutrophil count (ANC) >= 1000/mm^3
- •Hemoglobin (Hgb) >= 10 mg/dl
- •Platelets >= 75,000/mm^3
- •Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
- •Total bilirubin =< 2.5 mg/dl
- •Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 times upper limit of normal (ULN)
- •Patients must be >= 18 years old
排除标准
- •Patients with any of the following cardiac conditions:
- •Symptomatic restrictive cardiomyopathy;
- •Unstable angina within 4 months prior to enrollment;
- •New York Heart Association functional class III-IV heart failure on active treatment
- •Patients with any contraindication to receiving rhuGM-CSF based products
- •Patients with any clinically significant autoimmune disease uncontrolled with treatment
- •Patients with a history of brain metastases must have a stable head imaging study within 30 days of eligibility determination; specifically, patients with active brain metastases will not be eligible for study
- •Patients who are simultaneously enrolled in any other treatment study
- •Pregnant or breast-feeding women
研究组 & 干预措施
Treatment (vaccine therapy)
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.
干预措施: HER-2/neu peptide vaccine (Biological)
Treatment (vaccine therapy)
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.
干预措施: leukapheresis (Procedure)
Treatment (vaccine therapy)
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.
干预措施: ex vivo-expanded HER2-specific T cells (Biological)
Treatment (vaccine therapy)
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.
干预措施: cyclophosphamide (Drug)
Treatment (vaccine therapy)
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.
干预措施: sargramostim (Biological)
Treatment (vaccine therapy)
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Evaluate Toxicity of Infusing HER2-specific T Cells as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
时间窗: Up to 4 months after first booster vaccine
Patients are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, complete blood counts, urine analysis and physical exams. All adverse events for all systems are graded on a scale of 1-5 and attribution is assigned. There are DLT criteria. DLT is defined as any incidence of Grade 3 hematologic and non-hematologic toxicity (excluding: fever, hypoxia, and urticaria) Thus, if a subject develops a Grade 3 toxicity (excluding those listed in Table 4) will be considered excessive toxicity and no further dose escalations will occur.
次要结局
- Proportion of Patients Whose T Cells Persist at a Level the Same or Greater as the Level After the Final T Cell Infusion and Subsequent Booster Immunizations as Assessed by IFN-gamma (IFN-g) ELISPOT(Up to 2 year following the last infusion)
- Development of CD4+ and CD8+ Epitope Spreading(Up to 2 years)
- Response of Skeletal or Bone-only Disease by FDG-PET and According to European Organization for Research and Treatment for Cancer (EORTC)(Up to 2 years)
研究者
Mary (Nora) Disis
Principal Investigator
University of Washington