A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of EGFRBi-armed autologous activated T-cells
研究概览
简要总结
RATIONALE: Giving autologous lymphocytes that have been treated in the laboratory with antibodies may stimulate the immune system to kill tumor cells. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving laboratory-treated autologous lymphocytes together with aldesleukin and GM-CSF may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated autologous lymphocytes when given together with aldesleukin and GM-CSF in treating patients with recurrent, refractory, or metastatic advanced solid tumors.
详细描述
OBJECTIVES:
Primary
Determine the safety and maximum tolerated dose of EGFRBi-armed autologous activated T-cells (ATC) when administered in combination with low-dose aldesleukin and sargramostim (GM-CSF) in patients with recurrent, refractory, or extensive (metastatic) advanced solid tumors.
Secondary
Assess clinical outcome based on tumor responses, overall survival, and progression-free survival.
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
- •Histologically or cytologically confirmed solid tumor type (ex. Head and Neck Squamous Cell Carcinoma, Colorectal, Pancreatic, Gastric, Esophageal, Renal, Prostate, Breast and Ovarian cancers, etc.); high risk, recurrent, refractory, or metastatic disease after ≥ 1 prior first-line regimen (chemotherapy or radiotherapy)
- •Documented EGFR-positive disease (any expression level) by immunohistochemistry (IHC)
- •No clinical evidence of active brain metastases; patients with brain metastases are eligible provided they have received definitive radiotherapy or chemotherapy and/or have undergone surgical resection for brain metastases
- •No prior hematological malignancy
- •Karnofsky performance status (PS) 60-100% OR RCOG PS 0-2
- •Life expectancy ≥ 3 months
- •Not pregnant or nursing
- •Fertile patients must use contraception
- •Granulocytes ≥ 1,000/mm3
- •Platelet count ≥ 50,000/mm3
- •Hemoglobin ≥ 8g/dL
- •BUN ≤ 2.0 times normal
- •Serum creatinine ≤ 2.0mg/dL
- •Bilirubin ≤ 1.5 times normal (with or without liver metastases)
- •Hepatitis B surface antigen and HIV negative
- •LVEF ≥ 45% at rest by MUGA
- •No evidence of depressed left ventricular function
- •No other malignancy, except for the following:
- •History of curatively treated in situ squamous cell carcinoma or basal cell carinoma of the skin
- •History of other curatively treated malignancy (except those with a hematologic origin) for with the patient has remained in complete remission > 5 years after completing therapy (as documented by history, physical exams, tumor markers, and radiology scanning)
排除标准
- •Serious medical or psychiatric illness that would preclude giving informed consent or receiving intensive treatment
- •Recent myocardial infarction (within the past year)
- •Current angina/coronary symptoms requiring medications
- •Clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA results)
- •Systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 m Hg; patients with elevated BP must have it controlled by anti-hypertensive medications for at least 7 days prior to the infusion
- •Clinical evidence of active brain metastases
- •Prior/Concurrent Therapy
- •More than 4 weeks since prior chemotherapy or radiotherapy
- •At least 4 weeks since prior cetuximab or small molecule EGFR-inhibitors including, but not limited to, gefitinib or erlotinib hydrochloride
- •No concurrent radiotherapy
- •No concurrent steroids except for treatment or adrenal failure, septic shock, or pulmonary toxicity or hormones for non-disease-related conditions(e.g., insulin for diabetes)
研究组 & 干预措施
Armed Activated T Cells
Activated T Cells (ATC) armed with the bispecific antibody OKT3 x Cetuximab (EGFRBi). ATC will be expanded for 14 days from a leukapheresis product, armed with EGFRBi, cryopreserved and infused in 8 divided doses. Patients will also receive low dose subcutaneous IL-2(3000,000 IU/m2/day) and GM-CSF (250ug/m2 twice per week)
干预措施: EGFRBi-armed autologous activated T cells (Biological)
结局指标
主要结局
Maximum tolerated dose of EGFRBi-armed autologous activated T-cells
时间窗: 5 week regimen with 2 month follow up
次要结局
- Determine potential side effects of treating patients with Armed Activated T Cells (ATC)(5 week regimen with 2 month follow up)
- Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro(5 week regimen with 2 month follow up)
- Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy(5 week regimen with 2 month follow up)
- Overall survival(5 week regimen wtih 2 month follow up)
- Progression-free survival(5 week regimen with 2 month follow up)
- Determination of immunologic changes by evaluation of peripheral blood lymphocytes(5 week regimen with 2 month follow up)