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

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorAzienda Ospedaliero-Universitaria di Parma

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • Diagnosis of MPN subtypes

    Diagnostic test

    Non-invasive imaging method (PET/CT) and flow-cytometry

Treatment groups

265 Participants
are divided into 1 treatment group
Group A: MPN subtypesExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Percentage of circulating CD34+/CCR2+ cells

Percentage of CD34+/CCR2+ cells among total CD34+ cells measured by flow cytometry in peripheral blood samples

Time frame
At study enrollment

Secondary outcomes

1

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

Time frame
At imaging session
2

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

Time frame
At imaging session
3

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

Time frame
At imaging session

Other outcomes

Sponsors and contacts

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