A Randomized Phase I/II Trial Using a GM-CSF-Producing and CD40L-Expressing Bystander Cell Line (GM.CD40L) Vaccine in Combination With CCL21 for Patients With Stage IV Adenocarcinoma of the Lung
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 73
- 试验地点
- 2
- 主要终点
- Phase II: Progression Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to find out what effects (good and bad) a tumor vaccine used in combination with GM.CD40L and CCL21 have on the patient and their cancer. We also want to find out if the vaccine and the drugs can boost the immune system of these patients and how their immune system reacts, both before and after the vaccine treatment.
详细描述
The vaccine will be made by mixing two kinds of cells: 1) some lung cancer cells, which have been grown in the lab, and 2) experimental "bystander (present but not taking part in the immune response)" cells. All the cells in the vaccine will be treated with high-dose X-rays to make sure that none of them grow and cause more cancer. The bystander cells are human cells that have been genetically changed to express GM-CSF and CD40L. These are called "GM.CD40L". (That is the original cells, called K562, with the genes for human GM-CSF and CD40L inserted into them). These changes are designed to help boost the participants' immune system to better fight the cancer in their body. GM-CSF is a hormone that is known to stimulate bone marrow to make more white blood cells.
CCL21 is a chemokine (protein) that helps to recruit T cells (a type of white blood cell that helps to protect the body from infections) and leads to hyper-responsive T cells. This leads to heightened immune responses when T cells are exposed to both CCL21 and antigen (a substance that when introduced into the body lead to production of an antibody)-presenting cells (A cell that can "present" antigen in a form that T cells can recognize it ). The induction of a strong cell-mediated immune response is the type of immunity expected to be most involved in controlling cancer cell growth. A randomized trial of a vaccine consisting of the GM.CD40L bystander cells and an equivalent number of allogeneic (taken from different individuals) tumor cells plus or minus CCL21 is proposed.
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
- 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 confirmed metastatic adenocarcinoma of the lung
- •Patients must have received and completed first line therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1
- •No external beam radiation therapy within 2 weeks of first vaccine administration
- •No stereotactic radiation therapy within 3 days of first vaccine
- •No targeted therapy within 2 weeks of first vaccine administration
- •No immunomodulatory therapy within 2 weeks of first vaccine administration
- •No chemotherapy within 4 weeks of first vaccine administration
- •During Screening period, no steroid therapy within 4 weeks of first vaccine administration
- •Patient's written informed consent
- •Adequate organ function (measured within a week of beginning treatment):
- •White blood count (WBC) > 3,000/mm³ and absolute neutrophil count (ANC) >/= 1500/mm³
- •Platelets > 100,000/mm³
- •Hematocrit > 25%
- •Bilirubin < 2.0 mg/dL
- •Creatinine < 2.0 mg/dL, or creatinine clearance > 60 mL/min
- •Patients will be tested for HLA-A0201 as determined by flow cytometry followed by molecular analysis of a peripheral blood specimen; however this result will not be an inclusion criterion.
- •Measurable metastatic tumor as defined by standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Lesions must be accurately measured in at least one dimension with the longest diameter ≥20 mm. With spiral computed tomography (CT) scan, lesion must be ≥10 mm in at least one dimension.
排除标准
- •Symptomatic brain metastasis or Uncontrolled central nervous system (CNS) metastasis will not be permitted.
- •Any acute medical problems requiring active intervention
- •Current corticosteroid (other than replacement doses in patients who are hypo-adrenal) or other immunosuppressive therapy
- •Any other pre-existing immunodeficiency condition (including known human immunodeficiency virus [HIV] infection)
- •Any known pre-existing autoimmune disorder
- •History of a second malignancy within the previous 2 years (except non-melanoma skin cancer and cervical in-situ)
- •Patients who have had major surgery without full recovery or major surgery within three weeks of the start of vaccine treatment
- •Pregnant or lactating women: Patients in reproductive age must agree to use contraceptive methods for the duration of the study (*A pregnancy test will be obtained before treatment).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2, 3, or 4
- •Patients with other significant diseases or disorders that, in the Investigator's opinion, would exclude them from the study.
- •Patients who at the discretion of the investigator are deemed to have rapidly progressive disease
研究组 & 干预措施
Phase I Vaccinations
Participants enrolled in the Phase I trial will receive GM.CD40L.CCL21 vaccinations on 3 occasions, at 2 week intervals. Note for the phase I portion: the use of steroid medication is to be avoided for 4 weeks prior to the initiation of vaccine therapy and during the vaccine treatment period.
干预措施: Phase I - GM.CD40L.CCL21 Vaccinations (Biological)
Phase II Arm A Vaccinations
Arm A participants will receive GM.CD40L cells vaccinations on 3 occasions, at 2 week intervals. Note on either Arms A and B: the use of steroid medication is to be avoided for 4 weeks before to the initiation of vaccine therapy and during the vaccine treatment period.
干预措施: Phase II - GM.CD40L cells Vaccinations (Biological)
Phase II Arm B Vaccinations
Arm B participants will receive GM.CD40L.CCL21 vaccinations on 3 occasions, at 2 week intervals. Note on either Arms A and B: the use of steroid medication is to be avoided for 4 weeks before to the initiation of vaccine therapy and during the vaccine treatment period.
干预措施: Phase II - GM.CD40L.CCL21 Vaccinations (Biological)
结局指标
主要结局
Phase II: Progression Free Survival (PFS)
时间窗: Up to 6 Months
PFS is measured as the time from start of treatment to progression or death. 6 month progression free survival will be estimated from available clinical and radiographic assessments and RECIST 1.1 will be used to make tumor measurements. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions.
Phase I: Recommend Phase II Dose (RPDII)
时间窗: Up to 6 Months
Highest dose level of GMCD40L vaccine in combination with CCL21 that induced dose limiting toxicity (DLT) in fewer than 33% of patients. DLT: Intervention-specific acute toxicity; i.e., occurrence within 28 days of drug administration, according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), V 4: 1.) that precludes further dose escalation. Participants are entered in cohorts of 3 at the first dose level. Doses are not escalated over the course of treatment of an individual patient. If 2 or more patients experience toxicity in dose level 1 (30X10\^6 cells per injection), dose de-escalation will occur. Dose level -1 will be defined by 10 % reduction of cells administered from dose level 1 and follow the same rules. It is not feasible to escalate the dose of the vaccine beyond 30X10\^6 cells per injection; therefore the Maximum Tolerated Dose (MTD) may not be reached in this study. In that case, the highest dose level will be used in the phase II component.
次要结局
- Response Rate(Up to 12 Months)