A Safety and Feasibility Trial of Boost Vaccinations of a Lethally Irradiated, Allogeneic Pancreatic Tumor Cell Vaccine Transfected With the GM-CSF Gene Given Alone or in Combination With Either a Single Intravenous Dose or Daily Metronomic Oral Doses of Cyclophosphamide for the Treatment of Surgically Resected Pancreatic Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 71
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation
研究概览
简要总结
The purpose of this study is to evaluate the safety and feasibility of long term boost vaccination of a lethally irradiated, allogenic pancreatic tumor cell vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene (GVAX Pancreas Vaccine) alone or given in combination with either a single intravenous dose or daily metronomic oral doses of cyclophosphamide for the treatment of patients with surgically resected adenocarcinoma of the pancreas.
详细描述
Primary Objective:
- To evaluate the safety and feasibility of long term boost vaccinations of a lethally irradiated, allogeneic pancreatic tumor cell vaccine transfected with the GM-CSF gene given alone or in combination with either a single intravenous dose or daily metronomic oral doses of cyclophosphamide for the treatment of patients with surgically resected adenocarcinoma of the head, neck, or uncinate process of the pancreas.
Secondary Objective:
- To assess the effect of boost vaccinations and long-term treatment of immune modulating doses of cyclophosphamide on the number, repertoire and avidity of peripheral mesothelin-specific CD8+ T cells.
- To estimate disease-free and overall survival of surgically resected pancreatic adenocarcinoma patients treated with vaccine boosts with or without low dose cyclophosphamide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Has a history of surgically resected and pathologically proved AJCC stage I or stage II adenocarcinoma of the head, neck, or uncinate of the pancreas.
- •Cohorts 1, 3, 4 and 5: Have been a participant in Hopkins IRB protocol J0810, J1568, J15237 or J
- •Cohort 2: Have never received any type of pancreatic cancer vaccine/immunotherapy, had the Whipple surgery within 18 months and completed the planned adjuvant chemotherapy and/or chemoradiation.
- •Cohorts 1, 3, 4 and 5: Received the last irradiated GM-CSF transfected allogeneic pancreatic cell lines Panc 10.05 and Panc 6.03 at least 6-12 months prior.
- •Has received the last anti-cancer therapy at least 28 days ago.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Has provided informed consent.
- •Has adequate hematologic function.(Hemoglobin ≥ 9 g/dL ANC ≥ 1500/mm3 Platelets ≥ 100,000 K/ mm3).
- •Has adequate renal function (Serum creatinine ≤ 2 mg/dL).
- •Has adequate hepatic function. (Bilirubin ≤ 2.0 mg/dl, unless known Gilbert's Syndrome; AST, ALT and amylase ≤ 2x upper limit of normal, Alk Phos ≤ 5x upper limit of normal).
- •Agree to use adequate birth control, if of childbearing potential.
排除标准
- •Has radiographic evidence of pancreatic cancer recurrence.
- •Has any documented history of autoimmune diseases including systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis,or vasculitis.
- •Has any uncontrolled medical problems.
- •Has had systemic steroid therapy within 28 days before vaccine administration.
- •Has an anticipated need for systemic steroid therapy within 28 days after vaccine administration.
- •Has any evidence of active infections.
- •Is pregnant.
- •Has a history of another cancer (other than pancreatic cancer) or myeloproliferative disorders in the past five years except for treated non-melanoma skin cancer, superficial bladder cancer, or carcinoma in-situ of the cervix.
- •Has a history of noncompliance during previous vaccination cycles with study treatment and/or monitoring which is concerning for continued noncompliance.
研究组 & 干预措施
Cohort 1 (J0810 Arm A)
Patients coming from J0810 (NCT00727441). Patients receive GVAX.
干预措施: GVAX Pancreas Vaccine (Biological)
Cohort 1 (J0810 Arm B)
Patients coming from J0810 (NCT00727441). Patients receive IV CY and GVAX.
干预措施: Cyclophosphamide (Drug)
Cohort 1 (J0810 Arm B)
Patients coming from J0810 (NCT00727441). Patients receive IV CY and GVAX.
干预措施: GVAX Pancreas Vaccine (Biological)
Cohort 1 (J0810 Arm C)
Patients coming from J0810 (NCT00727441). Patients receive oral CY and GVAX.
干预措施: Cyclophosphamide Pill (Drug)
Cohort 1 (J0810 Arm C)
Patients coming from J0810 (NCT00727441). Patients receive oral CY and GVAX.
干预措施: GVAX Pancreas Vaccine (Biological)
Cohort 2 (Vaccine Naive)
Patients receive IV CY and GVAX.
干预措施: Cyclophosphamide (Drug)
Cohort 2 (Vaccine Naive)
Patients receive IV CY and GVAX.
干预措施: GVAX Pancreas Vaccine (Biological)
Cohort 3 (J1568)
Patients coming from J1568 (NCT02451982). Patients receive IV CY and GVAX.
干预措施: Cyclophosphamide (Drug)
Cohort 3 (J1568)
Patients coming from J1568 (NCT02451982). Patients receive IV CY and GVAX.
干预措施: GVAX Pancreas Vaccine (Biological)
Cohort 4 (J15237)
Patients coming from J15237 (NCT02648282). Patients receive IV CY and GVAX.
干预措施: Cyclophosphamide (Drug)
Cohort 4 (J15237)
Patients coming from J15237 (NCT02648282). Patients receive IV CY and GVAX.
干预措施: GVAX Pancreas Vaccine (Biological)
Cohort 5 (J1766)
Patients coming from J1766 (NCT03153410). Patients receive IV CY and GVAX.
干预措施: Cyclophosphamide (Drug)
Cohort 5 (J1766)
Patients coming from J1766 (NCT03153410). Patients receive IV CY and GVAX.
干预措施: GVAX Pancreas Vaccine (Biological)
结局指标
主要结局
Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation
时间窗: 121 Months
Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0
Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs)
时间窗: 121 months
Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0
次要结局
- Overall Survival (OS)(174 Months)
- Disease Free Survival (DFS)(131 months)