Clinical Assessment of a Therapeutic Vaccine in Combination With PD-1 Knockout T Cells in the Treatment of Prostate Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
研究概览
简要总结
This study is to evaluate the safety and efficacy of a therapeutic vaccine in combination with PD-1 knockout T cells in the treatment of advanced prostate cancer.
详细描述
This is a phase 1/2 clinical study investigating the safety and efficacy of a therapeutic vaccine in combination with PD-1 knockout T cells in the treatment of advanced prostate cancer. The therapeutic vaccine is a customized product involving ex vivo treatment of the patient's peripheral blood mononuclear cells with a recombinant fusion protein (PAP-GM-CSF) to activate the expression of the antigen that would activate the immune function to kill cancer cells. The PD-1 knockout engineered T cells are also prepared using patient's T cells in which PD-1 gene will be knocked out using CRISPR Cas9 technology. The therapeutic vaccine and PD-1 knockout T cells will be infused back to the patient in 3 times with a 2-week interval.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •• Histologically confirmed prostate cancer (stage IV, according to NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer, Version 2.2017)
- •Evidence of metastasis in the soft tissue and/or bone.
- •Progressive androgen independent castrate resistant prostate cancer.
- •Serum PSA ≥ 5.0 ng/mL
- •Estimated life expectancy ≥ 6 months.
- •Castrate level of testosterone (< 50 ng/dL) achieved via medical or surgical castration.
- •Adequate hematologic, renal and liver function.
排除标准
- •• Presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites.
- •Presence of moderate to severe pain treating with opioid analgesics within 21 days prior to registration.
- •ECOG score ≥
- •Any other systemic therapy for prostate cancer (except for medical castration).
- •Participation in previous study using Provenge (Sipuleucel-T) or similar product.
- •Known pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression.
- •Known malignancies other than prostate cancer requiring active treatment within 6 months.
- •A requirement for systemic immunosuppressive therapy for any reason.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to this product or granulocyte-macrophage colony-stimulating factor.
- •Any infection requiring parenteral antibiotic therapy or causing fever (temp > 100.5°F or > 38.1°C) within 1 week prior to registration.
- •Any medical intervention or other condition which, in the opinion of the Principal Investigator could compromise adherence with study requirements or otherwise compromise the study's objectives.
- •Treatment with any of the following medications or interventions within 28 days of registration:
- •Systemic use of corticosteroids, External beam radiation therapy or surgery, Use of non-steroidal antiandrogens Dietary and herbal supplements, as well as alternative treatments that have evidence of hormonal and/or anticancer properties (e.g., prostate cancer (PC) -SPES or PC-SPEC) and saw palmetto, Megestrol acetate (Megace®), diethylstilbesterol (DES), or cyproterone acetate, ++Ketoconazole, 5-alpha-reductase inhibitors, Treatment with any other investigational product Treatment with chemotherapy High dose calcitriol [1,25(OH)2Vitamin D] (i.e., > 0.5 mcg/day). Initiation or discontinuation of bisphosphonate therapy
研究组 & 干预措施
Therapeutic vaccine
Therapeutic vaccine will be prepared ex vivo using the peripheral mononuclear cells from the patients and the vaccine (as maturated dendritic cells) will be infused back to the patients in 3 times with a 2-week interval.
干预措施: Therapeutic vaccine (Biological)
Therapeutic vaccine plus PD-1 knockout
Therapeutic vaccine and PD-1 knockout T cells will be prepared ex vivo using the white cells from the patients and the vaccine (as maturated dendritic cells) and maturated PD-1 knockout T cells will be infused back to the patients in 3 times.
干预措施: Therapeutic vaccine (Biological)
Therapeutic vaccine plus PD-1 knockout
Therapeutic vaccine and PD-1 knockout T cells will be prepared ex vivo using the white cells from the patients and the vaccine (as maturated dendritic cells) and maturated PD-1 knockout T cells will be infused back to the patients in 3 times.
干预措施: PD-1 Knockout T Cells (Biological)
PD-1 knockout T cells
PD-1 knockout T cells will be prepared ex vivo using the white cells from the patients and the maturated PD-1 knockout T cells will be infused back to the patients in 3 times.
干预措施: PD-1 Knockout T Cells (Biological)
结局指标
主要结局
Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
时间窗: 6 months
Safety and tolerability of dose of therapeutic vaccine in combination with PD-1 Knockout T cells will be assessed using CTCAE v4.0
次要结局
- Response Rate(6 months)
- Progression free survival - PFS(Up to 12 months)
- Overall Survival - OS(Death)
- Peripheral blood circulating tumor DNA(8 weeks)
研究者
Size Chen
Professor
The First Affiliated Hospital of Guangdong Pharmaceutical University