a phase ii clinical trial of flonoltinib maleate tablet in intermediate-high risk myelofibrosis

Conditions: MF,PMF,PPV-MF,PET-MF

Summary: this trial adopts a multicenter, open-label, positive drug parallel control clinical trial design, planning to enroll approximately 75 mf participants. eligible participants will be stratified and assigned in a 1:1:1 ratio to the low-dose flonoltinib maleate tablet group, high-dose flonoltinib maleate tablet group, or the ruxolitinib tablet group. stratification factor include the dynamic international prognostic scoring system (dipss) risk classification (intermediate-2 and high risk)


Eligibility criteria:
inclusion criteria: 1. age ≥ 18 years, no gender restrictions; 2. diagnosed with primary myelofibrosis (pmf) according to who criteria (2016 edition) or post-polycythemia vera myelofibrosis (ppv-mf) or post-essential thrombocythemia myelofibrosis (pet-mf) according to iwg-mrt criteria; 3. evaluated as intermediate-2 or high-risk myelofibrosis according to the dynamic international prognostic scoring system (dipss) risk classification; 4. expected survival ≥ 24 weeks; 5. ecog score of 0-2; 6. splenomegaly: palpable spleen edge reaching or exceeding 5 cm below the costal margin (distance from the intersection of the left midclavicular line and the left costal margin to the farthest point of the spleen); or not palpable due to body habitus (obesity) but confirmed by magnetic resonance imaging (mri ) (or ct scan if necessary) at screening with spleen volume ≥ 450 cm³; 7. blasts in peripheral blood and bone marrow ≤ 10%; 8) within 7 days before the first dose, absolute absolute neutrophil count (anc )≥ 1.0×10\^9/l, platelet count ≥ 50×10\^9/l, hemoglobin (hgb )\> 60 g/l (participants should not have received growth factors, colony-stimulating factors, thrombopoietic agents, or platelet transfusions within 2 weeks before the baseline assessment prior to the first dose); 9) major organ function basically normal within 7 days before the first dose; 10) able to understand and voluntarily sign the informed consent form. exclusion criteria: 1. previous anticancer treatment-related toxic reactions have not recovered to grade 1 or below (excluding alopecia and conditions specified in inclusion criteria 8 and 9), or have not fully recovered from previous surgery (major surgery within 4 weeks); 2. hypersensitivity, allergic to the investigational drug or its excipients; 3. previous intolerance or resistance to ruxolitinib; 4. use of jak inhibitors within 4 weeks before the first dose; 5. any significant clinical and laboratory abnormalities that, in the investigator's opinion, affect safety evaluation; 6. history of congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accident (excluding lacunar infarction), or pulmonary embolism within 6 months prior to screening; 7. impaired cardiac function or arrhythmic disease requiring treatment at screening; 8. any active infection requiring intravenous antibiotic treatment at screening; 9. active tuberculosis infection within 48 weeks prior to screening or latent tuberculosis infection indicated by tuberculosis-related tests during the screening period; 10. patients who have undergone splenectomy or received radiation therapy to the spleen area within 12 months before the first dose; 11. active hepatitis b virus (hbv) or hepatitis c virus (hcv) infection, except for: a) hbv infection: patients with positive hepatitis b surface antigen (hbsag) or hepatitis b core antibody (hbcab) with undetectable peripheral blood hbv-dna (below the detection limit of the testing laboratory) can be enrolled; they must continue antiviral therapy and have hbv-dna testing every 12 weeks and at the end of treatment (eot); b) hcv seropositive patients with negative hcv rna can be enrolled. 12. positive for human immunodeficiency virus antibody (hiv-ab) or treponema pallidum antibody (tp-ab) (patients with positive treponema pallidum antibody can have a titer test, and the investigator will determine eligibility based on comprehensive judgment); 13. patients with epilepsy or those using psychiatric drugs or sedatives at screening (excluding those used for sleep purposes); 14. pregnant or breastfeeding women, and patients with reproductive potential (male and female) who refuse to use contraceptive measures during the trial and for 6 months after the trial; 15. patients who have had another malignancy within 5 years before the first dose (excluding cured in-situ carcinoma and basal cell carcinoma of the skin); 16. patients with other severe diseases that, in the investigator's opinion, may affect safety or compliance; 17. patients who participated in other clinical trials of investigational drugs or medical devices within 1 month before the first dose and used the investigational drug or device; 18. use of any treatment for mf (other than jak inhibitors) within 2 weeks or 5 half-lives (whichever is longer) before the first dose, any immunomodulatory agents (e.g., thalidomide), any immunosuppressants, ≥10 mg/day prednisone or equivalent biological potency corticosteroids, or growth factors (e.g., erythropoietin (epo)) (traditional chinese medicine should be stopped 1 day before the first dose); 19. patients with a history of congenital or acquired bleeding disorders; 20. other factors that the investigator deems unsuitable for participation in the trial.