A Phase I Study Evaluating the Feasibility of Using Fluorine-19 Cell Sense to Image Human Peripheral Blood Mononuclear Cells In Vivo
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 2
- 主要终点
- Number of participants with treatment-related adverse effects as assessed by CTCAE v4.0
研究概览
简要总结
Cell-based therapies in the form of stem cell-based or immune cell-based therapies are becoming important treatment options that are either approved for clinical use or are showing promise in clinical trials. One of the issues regarding cell-based therapies is that, once the cells are injected into a subject, there is no easy way to track where they go, assess whether adequate numbers of cells arrive at the intended therapeutic target and for how long they persist at a given location. To address this issue non-invasive imaging methods have been developed using magnetic resonance imaging (MRI). When used with an appropriate cell labelling contrast agent, Cellular MRI can track cells non-invasively in vivo. Detection of cells is accomplished with an inert imaging agent containing the MRI sensitive fluorine-19 (19F) nuclei. The objective of this study is to demonstrate that 19F-MRI is safe to use in humans so that it can subsequently be used to track cell-based immunotherapies in future clinical trials. The long term goal is to be able to quantify immune cell migration to secondary lymphoid tissues and potentially to tumors and correlate to therapeutic outcomes.
详细描述
Background: None of the currently available Good Manufacturing Practices (GMP)-grade MRI cell labelling agents are approved for use in Canada. There is one iron oxide nanoparticle GMP grade preparation that is commercially available but it is not suitable for labelling the immune cell populations the investigators are interested in tracking in vivo. The investigators have, instead, chosen to develop the commercially available, GMP-grade 19F-based perfluorocarbon, known as Cell Sense, for the purpose of tracking immune cell-based vaccine therapies in vivo. This agent has been successful used in a phase I clinical trial in United States and is approved for a second trial current recruiting, under the oversight of the FDA.
The cell tracing agent Cell Sense (CS-1000) is an inert, non-metabolizable tracer. As CS-1000 is taken-up and incorporated into the cell traditional pharmacodynamic and pharmacokinetic analyses in animals and humans are not appropriate, as adsorption and biodistribution will vary with cell type, and therefore have not been done. In vitro studies of toxicity towards various cell types did not yield evidence of adverse effects on various cell functions. Cell Sense also was shown to be non-mutagenic using the Ames and Forward thymidine kinase (TK) assays. Some limited skin irritation was observed when >2,500 fold more Cell Sense than expected to be maximally injected into humans was injected intradermally into rats.
Examples of MRI cell tracking labels include superparamagnetic iron oxide nanoparticles and 19F-containing compounds such as perfluorocarbons. The advantage of using cellular MRI to track cells is that a non-radioactive tracer is used that is suitable for longitudinal studies. MRI offers 3D imaging with exquisite soft tissue contrast. The additional advantage of using 19F over iron-based agents is that 19F is a positive, easily quantifiable contrast cell labelling agent. Furthermore, there is no 19F-background MRI signal in humans whereas MRI involving iron can be confounded by different imaging artifacts and it is a negative contrast agent that is difficult to accurately quantify. The investigators are particularly interested in whether immune cells arrive in secondary lymphoid organs such as lymph nodes.
Study Design:
Open label, dose escalating, single centre, phase I study that will accrue (a) 6 healthy adults and (b) 6 prostate cancer patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men diagnosed with confirmed adenocarcinoma of the prostate
- •No history of skin hypersensitivities or allergies.
- •Normal liver functions as defined by alanine aminotransferase (ALT) (3-36 U/L) and aspirate aminotransferase (AST) levels (10-34 U/L)
- •Normal kidney function by monitoring urea (2.5-8.0 ηmol/L) and creatine (70-120 μmol/L [for males]) concentrations.
- •Normal complete blood count with differential
- •Body Weight between 40 and 110 kg (relates to being able to fit in scanner)
- •Body Mass Index < 30 (relates to being able to fit in scanner)
- •Negative for (HIV, HTLV1&2, Hep A, B, C, syphilis) infection as determined by approved serological testing.
排除标准
- •Contraindication to venipuncture and donation of 100-160 mL of blood
- •Active infection (not limited to HIV, HTLV1&2, Hep A, B, C, syphilis)
- •Participants are on active chemotherapy (not including castrate hormone therapy), radiation therapy or immunosuppressive therapy (i.e. steroid use, anti-transplant rejection drugs, depleting antibodies)
- •Participants who are unable to have an MRI scan (e.g. history of head or eye injury involving metal fragments, implanted electrical device (such as a cardiac pacemaker), conductive implants or devices such as skin patches, body piercing or tattoos containing metallic inks, severe heart disease (including susceptibility to heart rhythm abnormalities), claustrophobia, etc.)
- •Participants with known allergies to phenol red, β-lactams and β-lactam derivative
- •Participants with known allergies to streptomycin sulfate and gentamicin sulfate
- •Participants with unforeseen conditions that are deemed unsafe or inappropriate for the study (e.g. participants who are claustrophobic and cannot undergo an MRI) as per the discretion of the principal investigator.
结局指标
主要结局
Number of participants with treatment-related adverse effects as assessed by CTCAE v4.0
时间窗: 12 months
次要结局
- Number of patients with detectable 19F MRI signal at local lymph nodes(24 hours post injection)
- Number of patients with detectable 19F MRI signal at the site of injection(1hr post injection)
研究者
Gregory A. Dekaban
Professor
Western University, Canada