NCT00923806终止1 期
Phase I/II Study of Metastatic Cancer That Expresses Carcinoembryonic Antigen (CEA) Using Lymphodepleting Conditioning Followed by Infusion of Anti-CEA TCR-Gene Engineered Lymphocytes
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- clinical response of the administration of anti-CEA TCR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative conditioning regimen and aldesleukin in patients with metastatic cancer.
研究概览
简要总结
Background:
- Carcinoembryonic antigen (CEA) is a protein present mostly in cancer cells.
- An experimental procedure developed for treating patients with cancer uses blood cells found in their tumors or bloodstream. These cells are genetically modified using the anti-CEA gene and a type of virus. The modified cells (anti-CEA cells) are grown in the laboratory and then given back to the patient to try to decrease the size of the tumors. This is called gene therapy.
Objectives:
- To determine whether advanced cancers that that express the CEA antigen can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-CEA protein.
Eligibility:
- Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site) and for whom standard treatments are not effective.
- Patients' tumors express the CEA antigen.
- Patients have the human leukocyte (HLA-A*0201) antigen.
Design:
- Workup with scans, x-rays and other tests.
- Leukapheresis to obtain cells for preparing the anti-CEA cells for later infusion.
- 1 week of chemotherapy to prepare the immune system for receiving the anti-CEA cells.
- Infusion of anti-CEA cells, followed by interleukin-2 (IL-2) treatment. The cells are given as an infusion through a vein. IL-2 is given as a 15-minute infusion through a vein every 8 hours for a maximum of 15 doses.
- 1-2 weeks of recovery from the effects of chemotherapy and IL-2.
- Periodic follow-up clinic visits after hospital discharge for physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.
详细描述
Background:
- We have constructed a single retroviral vector that contains both the alpha and beta chains of a T cell receptor (TCR) that recognizes the carcinoembryonic antigen (CEA), which can be used to mediate genetic transfer of this TCR with high efficiency (greater than 30%) without the need to perform any selection.
- In co-cultures with HLA-A2 and CEA positive tumors, anti-CEA TCR transduced T cells secreted significant amounts of interferon-gamma (IFN-gamma) with high specificity.
Objectives:
Primary objectives:
- To evaluate the safety of the administration of anti-CEA TCR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative conditioning regimen and aldesleukin.
- To determine if the administration of anti-CEA TCR engineered peripheral blood lymphocytes and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic cancer that expresses CEA.
- To determine the in vivo survival of TCR gene-engineered cells.
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
- •INCLUSION CRITERIA:
- •Metastatic cancer that expresses carcinoembryonic antigen (CEA) as assessed by one of the following methods:
- •Immunohistochemistry of resected tissue, assessed by immunohistochemistry (IHC) in the Clinical Laboratory Improvement Amendments (CLIA) approved test in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH). Since the affinity of the antibody is weak, a result of greater than or equal to 1+ is considered positive.
- •Detection of elevated levels of circulating CEA using a standard clinical enzyme-linked immunosorbent (ELISA) assay. Results will be considered positive if CEA level is greater than 10 mcg/L.
- •Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the NCI.
- •Hepatic metastases must represent the life limiting components of the disease defined as liver disease with a very high likelihood of causing the death of a patient according to the best clinical judgment of the attending physician.
- •Patients must have previously received systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred.
- •Greater than or equal to 18 years of age.
- •Willing to sign a durable power of attorney
- •Able to understand and sign the Informed Consent Document
- •Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or
- •Life expectancy of greater than three months.
- •Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
- •Patients must be human leukocyte antigen (HLA-A*0201) positive
- •Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
- •Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
- •Hematology:
- •Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
- •White blood cell (WBC) (greater than 3000/mm^
- •Platelet count greater than 100,000/mm^
- •Hemoglobin greater than 8.0 g/dl.
- •Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
- •Serum creatinine less than or equal to 1.6 mg/dl.
- •Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- •More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
排除标准
- •Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- •Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- •Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- •Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- •Concurrent systemic steroid therapy
- •History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- •History of coronary revascularization or ischemic symptoms
- •Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
- •Documented LVEF of less than or equal to 45% tested in patients with:
- •History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
- •Age greater than or equal to 60 years old
- •Documented forced expiratory volume (FEV1) less than or equal to 60% predicted tested in patients with:
- •A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
- •Symptoms of respiratory dysfunction
研究组 & 干预措施
Gene Therapy Treatment
Experimental
干预措施: PG13-CEA_TCR (Anti-CEA TCR PBL) (Biological)
Gene Therapy Treatment
Experimental
干预措施: Aldesleukin (Drug)
结局指标
主要结局
clinical response of the administration of anti-CEA TCR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative conditioning regimen and aldesleukin in patients with metastatic cancer.
次要结局
- Safety
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)
研究点 (1)
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