NCT00569296终止1 期
A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Non-Small Cell Lung Cancer
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro
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 non-small cell lung cancer.
FUNDING SOURCE--FDA OOPD
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) non-small cell lung cancer (NSCLC).
Secondary
- Assess clinical outcome based on tumor responses, overall survival, and progression-free survival.
- Monitor changes in sera concentrations of the tumor marker in association with EGFRBi-armed ATC administration throughout the study and at time points thereafter in patients with elevated levels of carcinoembryonic antigen (CEA) prior to beginning the study.
- Monitor patient sera for human anti-mouse antibodies (HAMA).
- Evaluate immune response, which may reflect immune augmentation in response to EGFRBi-armed ATC infusions, in peripheral blood mononuclear cell (PBMC) samples as well as purified immune cell populations.
- Investigate proliferation in response to ex vivo stimulation with NSCLC tumor-associated antigens, sera cytokine profiles (Th1 vs Th2), cytotoxicity of patient PBMC, and interferon gamma ELISPOTS as a surrogate marker for assessing generation of EGFR-specific cytotoxic T-lymphocytes (CTL).
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 or cytologically confirmed non-small cell lung cancer (NSCLC)
- •Recurrent, refractory, or metastatic disease after ≥ 1 prior first-line regimen (chemotherapy or radiotherapy)
- •Documented EGFR-positive disease (any expression level) by immunohistochemistry (IHC) (may be based on archival sample)
- •Measurable or evaluable disease by radiograph, CT scan, MRI, and/or physical exam
- •Appropriate slides of the primary lesion must be available for review of IHC staining assessment by a central pathology team
- •No clinical evidence of active brain metastases
- •Patients with brain metastases are eligible provide they have received definitive radiotherapy or chemotherapy and/or have undergone surgical resection for brain metastases
- •No prior hematological malignancy
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status (PS) 60-100% OR ECOG PS 0-2
- •Life expectancy ≥ 3 months
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Granulocytes ≥ 1,000/mm^3
- •Platelet count ≥ 50,000/mm^3
- •Hemoglobin ≥ 8 g/dL
- •BUN ≤ 2.0 times normal
- •Serum creatinine ≤ 2.0 mg/dL
- •Bilirubin ≤ 1.5 times normal
- •SGOT ≤ 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
- •FEV_1, DLCO, and FVC ≥ 50% of the predicted value
- •No other malignancy, except for the following:
- •History of curatively treated in situ squamous cell carcinoma or basal cell carcinoma of the skin
- •History of other curatively treated malignancy (except those with a hematologic origin) for which the patient has remained in complete remission > 5 years after completing therapy (as documented by history, physical exams, tumor markers, and radiology scanning)
- •No serious medical or psychiatric illness that would preclude giving informed consent or receiving intensive treatment
- •No recent myocardial infarction (within the past year)
- •No current angina/coronary symptoms requiring medications
- •No clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA results)
- •No systolic blood pressure (BP) ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg
- •Patients with elevated BP must have it controlled by anti-hypertensive medications for at least 7 days prior to the first infusion
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •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 of adrenal failure, septic shock, or pulmonary toxicity or hormones for non-disease-related conditions (e.g., insulin for diabetes)
排除标准
- 未提供
研究组 & 干预措施
T-cells
Experimental
EGFRBi-armed autologous activated T cells
干预措施: EGFRBi-armed autologous activated T cells (Biological)
T-cells
Experimental
EGFRBi-armed autologous activated T cells
干预措施: sargramostim (Biological)
T-cells
Experimental
EGFRBi-armed autologous activated T cells
干预措施: aldesleukin (Biological)
结局指标
主要结局
Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro
时间窗: 4 weeks
Safety
时间窗: 4 weeks
Maximum tolerated dose of EGFRBi-armed autologous activated T-cells
时间窗: 4 weeks
次要结局
- Evaluation of tumor markers and human anti-mouse antibody responses as assessed by carcinoembryonic antigen (CEA) levels in serum samples and development of IgG and IgM anti-mouse antibody responses to the Bi-antibodies(4 weeks)
- Determination of immunologic changes by evaluation of peripheral blood lymphocytes(4 weeks)
- Determination of immunologic changes by evaluation of cytotoxic T-lymphocytes as measured by interferon gamma ELISPOTS directed at autologous tumor or lung cancer cell lines(4 weeks)
- Progression-free survival(2 years)
- Overall survival(2 years)
- Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy(4 weeks)
研究者
研究点 (1)
Loading locations...
相似试验
终止
1 期
Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and Sargramostim (GM-CSF) in Treating Advanced Solid TumorsNeoplasmsTumorsMetastatic CancerSolid TumorsNCT01081808Roger Williams Medical Center2
招募中
1 期
CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid LeukemiaRecurrent Adult Acute Myeloid LeukemiaRefractory Acute Myeloid LeukemiaSecondary Acute Myeloid LeukemiaAcute Myeloid LeukemiaNCT05672147City of Hope Medical Center27
已完成
1 期
Adoptive Immunotherapy With Activated Marrow Infiltrating Lymphocytes and Cyclophosphamide Graft-Versus-Host Disease Prophylaxis in Patients With Relapse of Hematologic Malignancies After Allogeneic Hematopoietic Cell TransplantationHematologic MalignanciesGraft-Versus-Host DiseaseNCT02342613Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins32
招募中
1 期
Anti-CD19, Dual Co-stimulatory (4-1BB, CD3ζ) Chimeric Antigen Receptor T-cells in Patients With Relapsed/Refractory Aggressive Lymphoma or Acute Lymphoblastic Leukemia (ALL)Relapsed Non Hodgkin LymphomaRelapsed Adult ALLRelapsed Pediatric ALLNCT03938987University of Alberta63
撤回
1 期
Phase I/II Study of SLAMF7 FPBMC/CS-1 FPBMC in Relapsed/Refractory Multiple MyelomaMultiple MyelomaNCT04864522University of Virginia