A New Diagnostic Algorithm to Non-invasively Track Fibrotic Changes in Myeloproliferative Neoplasms Based on C-C Chemokine Receptor 2 Detection. From Flow Cytometry to the Development of Targeted Positron Emission Tomography Molecular Imaging. Pre-clinical Studies and First In-human Proof of Concept
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 265
- 试验地点
- 1
- 主要终点
- Percentage of circulating CD34+/CCR2+ cells
研究概览
简要总结
Chronic "Philadelphia-negative" myeloproliferative syndromes are chronic blood disorders. They include essential thrombocythemia, polycythemia vera, and myelofibrosis. Myelofibrosis may arise de novo ("primary myelofibrosis") or represent the evolution of essential thrombocythemia or polycythemia vera ("secondary myelofibrosis").
The myelofibrotic stage-characterized, as the name implies, by the presence of bone marrow fibrosis (deposition of scar-like tissue)-is generally associated with a more severe and symptomatic disease. To date, the only way to assess fibrotic progression in these disorders is bone marrow biopsy.
The aim of this project is to evaluate whether the identification, tracking, and quantification of cells expressing a specific receptor (CCR2), a selective biomarker of fibrosis, may allow early and non-invasive identification of the fibrotic stage of the disease through:
- laboratory analysis on a blood sample (using flow cytometry)
- use in PET-CT (positron emission tomography combined with computed tomography) of a tracer specific for the CCR2 receptor, capable of selectively binding to CCR2-expressing cells (⁶⁸Ga-DOTA-ECL1i).
详细描述
It is well established that the presence of bone marrow fibrosis in Philadelphia-negative myeloproliferative neoplasms (MPNs) defines a more severe disease stage, with a worse prognosis and a high risk of leukemic transformation. Therefore, accurate allocation of each patient to the correct diagnostic category is essential for subsequent therapeutic planning, which may also include bone marrow transplantation for selected patients.
To date, the only method available to assess bone marrow fibrosis is histopathological analysis of the bone marrow, which inevitably requires an invasive procedure such as bone marrow biopsy.
The aim of this project is to evaluate whether tracking and quantification of CD34⁺CCR2⁺ cells through flow cytometry (FCM) on peripheral blood and functional imaging may represent a valid non-invasive tool for identifying the fibrotic stage of the disease, thus supporting clinicians at key diagnostic time points, such as:
At disease onset, in support of histopathology for differential diagnosis when morphological features alone may be ambiguous (e.g., ET vs prePMF, unclassifiable MPNs); During follow-up, in cases of suspected progression of ET/PV to secondary myelofibrosis (SMF), as a screening tool prior to bone marrow biopsy; As an alternative to bone marrow biopsy, when clinical conditions do not allow the procedure.
To this end, the project is structured around the following AIMS:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 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
- •Diagnosis of ET/PV/prePMF/overtPMF according to the WHO 2016 criteria and of SMF according to the IWG-MRT criteria (with histopathological data).
- •Age >= 18 yrs
- •ECOG performance status <=3
排除标准
- •Pregnancy/breastfeeding
- •Ongoing therapy with immunomodulatory drugs (JAK-inhibitors, interferon).
- •For PET imaging, patients should be off any cytoreductive treatment for at least 3 months.
- •Antiplatelet agents are allowed
研究组 & 干预措施
MPN subtypes
Patient will be tested for CCR2 expression on CD34+ cells in order to correlate imaging and flow-cytometry data.
干预措施: Diagnosis of MPN subtypes (Diagnostic Test)
结局指标
主要结局
Percentage of circulating CD34+/CCR2+ cells
时间窗: At study enrollment
Percentage of CD34+/CCR2+ cells among total CD34+ cells measured by flow cytometry in peripheral blood samples
次要结局
- Volume of active bone marrow on 68Ga-DOTA-ECL1i PET/CT(At imaging session)
- Tracer uptake in extramedullary sites(At imaging session)
- Bone marrow SUVmax on 68Ga-DOTA-ECL1i PET/CT(At imaging session)
研究者
Elena Masselli
Principal Investigator
Azienda Ospedaliero-Universitaria di Parma