NCT05850273: IFN&SMP

Mechanism of Action of Interferon in the Treatment of Myeloproliferative Neoplasms

Recruiting now Last updated 14 April 2026

What this trial tests

trial in Myeloproliferative Neoplasm in 80 participants. Currently enrolling.

Timeline

16 March 2023

Primary endpoint
16 March 2028

16 March 2033

Quick facts

Lead sponsor	Institut National de la Santé Et de la Recherche Médicale, France
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	80
Start date	16 March 2023
Primary completion	16 March 2028
Estimated completion	16 March 2033
Sites	1 location across France

Conditions studied

• Myeloproliferative Neoplasm — all drugs for Myeloproliferative Neoplasm →

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France — full company profile →

Who can join

18 and older, any sex, with Myeloproliferative Neoplasm. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) include: Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are myeloid malignancies resulting from the transformation of a multipotent hematopoietic stem cell (HSC) caused by mutations activating the JAK2/STAT pathway. The most prevalent mutation is JAK2V617F. Type 1 and Type 2 calreticulin (CALR) and thrombopoietin receptor (MPL) mutations are also observed in ET and PMF. Additional non-MPN mutations affecting different pathways are also found, particularly in PMF, and are involved in disease initiation and/or in phenotypic changes and /or disease progression and/or response to therapy.

There is an obvious and urgent need for an efficient therapy for MPN. In particular, PMF remain without curative treatment, except allogeneic HSC transplantation and JAK inhibitors have limited effects on the disease outcome. Among novel therapeutic approaches, Peg-IFNα2a (IFN) is the most efficient harboring both high rates of hematological responses in JAK2V617F and CALRmut MPN patients and some molecular responses mainly in JAK2V617F patients including deep molecular response (DMR). Nevertheless, several studies, including our own, have demonstrated that the IFN molecular response in CALRmut patients is heterogeneous and overall much lower than in JAK2V617F patients. Moreover, some JAK2V617F MPN patients do not respond to IFN, and DMR is only observed in around 20% of JAK2V617F patients. Finally, long-term treatments are needed (2-5 years) to obtain a DMR, jeopardizing its success due to possible long-term toxicity.

The underlying reasons for failure, drug resistance, heterogeneous molecular response in CALRmut patients and the long delays for DMR in JAK2V617F patients remain unclear, largely because the mechanisms by which IFNα targets MPN malignant clones remain elusive.

Significant improvement of IFN efficacy cannot be achieved without basic and clinical research. Hence our two lines of research are to

* Understand how IFNα specifically targets neoplastic HSCs
* Predicting and improving patient response during IFNα therapy

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Single-cell RNA sequencing: enhancing the predictive accuracy of tumor immunotherapy efficacy.
   Zhou W, Huang Z, Wu Z, Tang M, et al · · 2025 · cited 3× · PMID 40857744 · DOI 10.1042/ebc20253017