Phase I/II Clinical Trial of Immunotherapy With an Allogeneic B7.1/HLA-A1 Transfected Tumor Cell Vaccine in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer That Have Completed First Line Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Preliminary Safety Profile (Phase 1)
研究概览
简要总结
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy and to see how well it works in treating patients with stage IIIB or stage IV non-small cell lung cancer who have finished first-line chemotherapy.
详细描述
OUTLINE: This is a multicenter study.
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Phase I (single site [University of Miami Sylvester Comprehensive Cancer Center]): Patients receive allogeneic B7.1 and human leukocyte antigen-A1 (HLA-A1) transfected tumor cell vaccine intradermally (ID) in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses. If no more than 1 of 6 patients experience a probable or definitively treatment related adverse effect (i.e., grade 2 autoimmune or grade 3-4 of any type), patients proceed to the phase II portion of the study. If 2 or more (out of 6) patients experience treatment related adverse effects the study stops.
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Phase II (randomized): Patients are stratified according to study site (University of Miami Sylvester Comprehensive Cancer Center or Memorial Regional Hospital), type of prior first-line treatment (platinum and taxane vs platinum and gemcitabine), and presence of brain metastasis (yes vs no). Patients are randomized to 1 of 2 treatment arms.
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Arm I: Patients receive allogeneic B7.1 and HLA-A1 transfected tumor cell vaccine ID in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses.
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Arm II: Patients receive a placebo vaccine as in arm I. Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for cluster of differentiation 8 (CD8), cluster of differentiation 4 (CD4), and natural killer cell (NK) response and peripheral blood lymphocytes (PBL) and T helper cell 1 (TH1)/T helper cell 2 (TH2) bias, including levels of interleukin (IL) IL-1β, IL-2, IL-4, IL-5, IL-6, IL-13, Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) via ELISA.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 4 years, and then once a year thereafter.
PROJECTED ACCRUAL: A total of 66 patients (6 patients for phase I and 60 patients for phase II) will be accrued for this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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 stage IIIB (non-candidates for radiation) or stage IV pathologically confirmed non-small cell carcinoma of the lung that completed 4-6 cycles of platinum based first line chemotherapy and achieved complete response (CR), partial response (PR) or stable disease.
- •Last administration of chemotherapy occurred no later than 4 weeks prior to the enrollment date.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Renal Requirements: The calculated creatinine clearance must be at least 50 ml/min.
- •Pulmonary Function Requirements:
- •All patients will undergo evaluation of pulmonary function prior to enrollment.
- •Patients should have a Forced expiratory volume in 1 second (FEV1) more than 30% of the predicted value and/or Diffusing capacity (DLCO) more than 30% of the predicted value with a partial pressure of carbon dioxide (PCO2) < 45mm.
- •Any patient enrolled in the protocol whose respiratory symptoms have experienced marked deterioration not related to a known cause (e.g. pneumonia, congestive heart failure (CHF) or pulmonary embolism (PE)) will have request pulmonary function test (PFT) evaluation and if the above parameters are seen will be excluded from the protocol.
- •Age ≥ 18 years.
- •Signed informed consent.
- •Patients should have absolute neutrophil count (ANC) ≥ 1000/mm3; platelets (PLT) ≥ 80,000/mm3.
排除标准
- •Small cell carcinoma of the lung.
- •Existing autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren's disease etc; colitis, inflammatory bowel disease or pancreatitis within 10 years of study.
- •Other active malignancies present within the past three years, except for basal and/or squamous cell carcinoma(s) or in situ cervical cancer.
- •Concomitant steroid or other immunosuppressive therapy.
- •Active infection, or less than 7 days since therapy for acute infections.
- •Pericardial effusion.
- •Currently receiving chemotherapy for another condition (such as arthritis).
- •Time elapsed greater than 4 weeks since last administration of first line chemotherapy for NSCLC.
- •Active or symptomatic cardiac disease such as congestive heart failure, angina pectoris or recent myocardial infarction.
- •Pregnant or lactating women (negative test for pregnancy required of women of childbearing potential).
- •Refusal in fertile men or women to use effective birth control measures during and for six months after the completion of treatment on study.
- •Known HIV infection
- •Untreated or uncontrolled brain metastasis.
- •Liver Enzymes greater than 3 times the institutional upper limit.
研究组 & 干预措施
Arm II: Placebo
Patients receive a placebo vaccine intradermally once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.
干预措施: Placebo (Other)
Arm I: Allogeneic B7.1/HLA-A1
Patients will receive Allogeneic B7.1/HLA-A1 vaccine once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.
Given intradermally.
干预措施: Allogeneic B7.1/HLA-A1 (Biological)
结局指标
主要结局
Preliminary Safety Profile (Phase 1)
时间窗: Up to 13 weeks
This will include the number of patients experiencing toxicity over the course of treatment, characterized by type of toxicity and grade, and by the time of toxicity onset in relation to day of vaccination.
Progression-free Survival (Phase 2)
时间窗: Date of randomization to the earliest date of documented progression.
次要结局
- Correlative Immunological Studies in Study Participants (Phase 2)(Baseline, Week 7 and Week 13)
- Safety Profile (Phase 2)(About 13 weeks)
- Immune Response (CD8) in B7-vaccinated Participants as Compared to Controls. (Phase 2)(About 13 weeks)
- Response to Second-line Chemotherapy After Disease Progression (Phase 2)(From Week 1 of Study Therapy until Death or Withdrawal of Consent)
- Relationship of CD8 Response in B7-vaccinated Patients to Their Progression-free Survival.(Phase 2)(From Week 1 of Study Therapy until Death or Withdrawal of Consent)
- Overall Survival (Phase 2)(Date of randomization to the recorded date of death)