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 (GR-MPN)

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).

Study Overview

• Status: Recruiting
• Conditions: Myelofibrosis (MF)
• Intervention / Treatment: Diagnostic test: Diagnosis of MPN subtypes

Detailed Description

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:

AIM 1 - Tracking of CD34⁺CCR2⁺ cells by flow cytometry as a diagnostic tool supporting histopathology in the differential diagnosis of MPN subtypes.

AIM 2 - Functional imaging of CCR2⁺ cells using the radioligand ⁶⁸Ga-DOTA-ECL1i in a murine model of myelofibrosis.

AIM 3 - Functional imaging of CCR2⁺ cells using the radioligand ⁶⁸Ga-DOTA-ECL1i in patients affected by MPNs.

• Study Type: Interventional
• Enrollment (Estimated): 265
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elena Masselli, MD, PhD; Phone Number: +39 0521 906655; Email: elena.masselli@unipr.it

Study Locations

• Italy
  • Italy
    • Parma, Italy, Italy, 43126
      • Recruiting
      • Dipartimento di Medicina e Chirurgia
      • Contact: Elena Masselli, MD, PhD; Phone Number: +39 0521 906655; Email: elena.masselli@unipr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MPN subtypes; Patient will be tested for CCR2 expression on CD34+ cells in order to correlate imaging and flow-cytometry data.	Diagnostic test: Diagnosis of MPN subtypes; Non-invasive imaging method (PET/CT) and flow-cytometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of circulating CD34+/CCR2+ cells	Percentage of CD34+/CCR2+ cells among total CD34+ cells measured by flow cytometry in peripheral blood samples	At study enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone marrow SUVmax on 68Ga-DOTA-ECL1i PET/CT	Maximum standardized uptake value (SUVmax) of 68Ga-DOTA-ECL1i in bone marrow regions measured by PET/CT imaging	At imaging session
Volume of active bone marrow on 68Ga-DOTA-ECL1i PET/CT	Volume of interest with tracer uptake above mean liver uptake plus two standard deviations measured by PET/CT imaging	At imaging session
Tracer uptake in extramedullary sites	Standardized uptake value and signal-to-background ratio of 68Ga-DOTA-ECL1i in extramedullary sites measured by PET/CT imaging	At imaging session

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria di Parma

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: February 16, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: MRI; PET; MRS; fluorescence; Myeloproliferative neoplasms; early detection of cancer; C-C chemokine receptor 2; therapy response monitoring; immunohystochemical assay; progression monitoring
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: 66/2023/SPER/AOUPR; GR-2021-12373308 (Other Grant/Funding Number: Ministero della Salute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No