The goal of this clinical trial is to learn if therapy can be improved in patients with myelofibrosis (MF) who have primary resistance or who have progressed after treatment with a Janus kinase (JAK) inhibitor or are intolerant for this category of drugs.
The main questions it aims to answer are:
* To evaluate the feasibility and safety of once daily dose of tasquinimod for 24 weeks (6 cycles) * To determine the optimal dose
Patients will be treated once daily with tasquinimod for a maximum period of 24 weeks (6 cycles).
During the study most (diagnostic) procedures are part of the standard of care. Different from standard of care:
* Participation may lead to extra visits to the outpatient clinic * Additional blood will be drawn when blood is already taken per standard of care * Bone marrow sampling at entry and at the end of the trial * MRI scans (or CT-scans) have to be performed * Quality-of-life questionnaires have to be filled out
Diagnosis of PMF or Post-PV MF or Post-ET MF based on a bone marrow (BM) biopsy not older than 6 months, according to the 2016 World Health Organization.
Refactory or intolerant to treatment with an approved JAK inhibitor or ineligible for JAK inhibitor treatment.
MF classified as Intermediate-1 with disease-related symptoms (e.g. symptomatic splenomegaly), Intermediate-2 or high-risk by Dynamic International Prognostic Scoring System Plus
Spleen ≥5 cm below costal margin as measured by palpation.
Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
Splenectomy.
Splenic irradiation within the last 6 months.
Prior allogeneic stem cell transplantation.
Single group
Tasquinimod
Drugtreatment with tasquinimod capsules once daily
SVR35W24
Proportion of patients with at least 35% reduction in spleen volume from baseline at Week 24 (SVR35W24) as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, per International Working Group (IWG) criteria, based on MRI review.
DLT phase I
To determine the dose limiting toxicity (DLT) of tasquinimod. Pre-defined adverse events (AEs) that occur within 28 days of the start of study treatment will be considered a DLT, unless the AE is definitely unrelated to tasquinimod.
RBC transfusions
Red blood cell (RBC) transfusion (number of packed cells) during tasquinimod treatment.
Changes in variant allele frequency
To determine the changes in variant allele frequency (VAF) of MPN driver genes after tasquinimod treatment by single cell and bulk DNA sequencing.
Change in splenomegaly
Proportion of patients with at least 50% reduction in palpable splenomegaly from baseline per IWG criteria.
Change in spleen volume by MRI review
Proportion of patients with at least 35% reduction in spleen volume from baseline (SVR35) as measured by MRI or CT scan, per IWG criteria, based on MRI review.
Plasma concentrations
Plasma concentrations of tasquinimod
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