Mechanism of Action of Interferon in the Treatment of Myeloproliferative Neoplasms

Recruiting now

Conditions studied: Myeloproliferative Neoplasm

In brief

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

Key facts

Study ID: NCT05850273
Run by: Institut National de la Santé Et de la Recherche Médicale, France
People needed: 80
Starts: 2023-03-16
Expected to finish: 2033-03-16
Last updated by the study team: 2026-04-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Adult male or female 18 years of age or older
Diagnosis of MPN has been previously established by the referring physician and that physician will have decided to treat with pegylated IFN. Patients will be treated or untreated at the time of inclusion and may be newly diagnosed patients.
These patients will be affiliated with or benefit from a social security plan
For all these patients an additional 20-40 mL will be collected except for some PV patients who are treated conventionally by phlebotomy. In this case, we will collect blood bags from these patients. The volumes vary between 300 and 450 mL of blood depending on the weight and size of the patients.
We will also include in this protocol any patient whose MPN, either PV, TE or MF, will have progressed to acute leukemia (AL) during treatment. These will be patients with AP of MPN (MPN can also progress to acute myeloid leukemia (AML) by acute transformation (AT) of MPN).
Patient with signed informed consent

You may not qualify if…

The non-inclusion criterion concerns the anemia that some MF patients may suffer from. Therefore, patients with anemia (Hb<10g) or transfusion dependency (≥ 1 packed red blood cell per month) at the time of the referral monitoring visit are not included in the research.
Persons under court protection, guardianship or curatorship

Where it is running

Inserm U1287 — Villejuif, Île-de-France Region, France (enrolling)

Full record on ClinicalTrials.gov

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