Flonoltinib Maleate Oral Regimens in Patients With Myelofibrosis

The goal of this clinical trial is to learn which of three different doses of Flonoltinib Maleate taken by mouth daily works best to treat adult patients with myelofibrosis in whom the most common approved therapy has failed to adequately control the disease. It will also learn about the safety of the three different daily doses of Flonoltinib Maleate. The main questions it aims to answer are: Which dose is the best at controlling the symptoms and signs of organ damage caused by myelofibrosis? What medical problems do participants have when taking the three different doses of Flonoltinib Maleate? Researchers will compare the three different doses of Flonoltinib Maleate to see which dose is best to treat patients with myelofibrosis. Participants will: Take Flonoltinib Maleate every day for as long as it seems to be of benefit to them in terms of controlling myelofibrosis. Visit the clinic for checkups and tests after giving fully informed written consent confirming that they would like to consider entering the study. Visit the clinic for checkups and tests when on the study once every 2 weeks for the first 2 months, every 4 weeks after that, and when coming off study therapy. Keep a diary of their symptoms.

Inclusion Criteria: All participants must: 1. Have signed the current relevant ICF prior to any study related procedures; 2. Understand and commit to comply with study requirements; 3. Be ≥18 years of age; 4. Be able to swallow and retain oral medications; 5. Be diagnosed with PMF according to the 2016 WHO criteria, or PPV-MF or PET-MF according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria; 6. Have Intermediate-1 to high-risk myelofibrosis (as per Dynamic International Prognostic Scoring System \[DIPSS\] risk categories) and be either JAKi-naïve or JAKi-resistant. JAKi-naïve patients include those with JAKi exposure of no more than 14 days. The JAKi-resistant patients need to meet 1 of the following criteria: a) Treatment with JAKi for 3 months with inadequate efficacy response defined as \< 10% spleen volume reduction (SVR) by Magnetic Resonance Imaging (MRI) or \60 g/L without the assistance of CSF, EPO, TPO, or component blood transfusions. Have discontinued growth factors and platelets transfusions for more than 2 weeks before screening tests; 14. Have no overt significant disease involving heart, lungs, liver, kidneys, or pancreas (left ventricular ejection fraction ≥ 45%; serum direct bilirubin ≤2 × upper limit of normal \[ULN\]; serum creatinine ≤1.5 × ULN or Estimated Glomerular Filtration Rate \[eGFR\] by the 2021 chronic kidney disease-Epidemiology Collaboration formula ≥ 45 mL/min/1.73 m2; alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\] ≤2.5 × ULN) or ≤5 × ULN if associated with liver MF involvement; 15. Have no severe coagulation dysfunction (prothrombin time \[PT\] or thrombin time \[TT\] ≤2 × ULN; activated partial thromboplastin time \[APTT\] ≤2 × ULN); 16. Have a normal thiamine level at the time of study entry; 17. Agree to comply with the relevant regulations of the treating institution and the research organization. Exclusion Criteria: Participants must not: 1. Have failure to recover from toxic effects of prior anticancer therapy to Grade 1 or below (except alopecia), or failure to fully recover from prior surgery (major surgery within 4 weeks); 2. Have known hypersensitivity to the investigational product or its excipients; 3. Have any significant clinical or laboratory abnormality that would interfere with accurate safety evaluation on study, including: 1. Uncontrolled diabetes with fasting blood glucose \>250 mg/dL (13.9 mmol/L); 2. Hypertension not controlled by one or two antihypertensive drugs to the following range: systolic \