A Clinical Trial of Flonoltinib Maleate for Intermediate or High-Risk Myelofibrosis

A Randomized, Open-label, Positive-controlled, Parallel-grouped, Multicenter Phase III Clinical Trial on the Efficacy and Safety of Flonoltinib Maleate Tablets in Patients With Intermediate- or High-risk Myelofibrosis

This trial adopts a multicenter, open label, positive drug parallel controlled clinical trial design, with a planned enrollment of approximately 105 participants in the MF trial. Successful trial participants were selected and assigned to either the experimental group or the control group in a 2:1 stratified manner, with the stratification factor being the Dynamic International Prognostic Scoring System (DIPSS) prognostic grading criteria. Continuously take the test drug/control drug until it meets the withdrawal criteria.

Inclusion Criteria:

1. Age range of 18-80 years old , gender not limited;
2. Patients diagnosed with primary myelofibrosis (PMF) according to WHO criteria (2016 edition) or patients diagnosed with post polycythemia vera myelofibrosis (PPV-MF) or post thrombocytopenia myelofibrosis (PET-MF) according to IWG-MRT criteria;
3. Expected survival period greater than 24 weeks;
4. ECOG score 0-2 points;
5. Splenomegaly: Palpation of the splenic margin reaching or exceeding 5cm below the rib ; Or due to physical reasons (such as obesity), it may not be palpable, but MRI/CT spleen evaluation during screening confirms a volume of >= 450 cm^3;
6. Within 7 days prior to randomization, the main organ functions were generally normal, meeting the following criteria: ALT and AST <= 2.5 × ULN; TBIL<=2.0×ULN； Serum creatinine <=1.5 × ULN or serum creatinine clearance rate (Ccr)>50 mL/min; INR, PT, and APTT <= 1.5 × ULN;
7. Can understand and voluntarily sign an informed consent form.

Exclusion Criteria:

1. The toxic reactions of previous anti-cancer treatments have not recovered to grade 1 or below (excluding hair loss), or have not fully recovered from previous surgeries;
2. Allergy to experimental drugs and their excipients;
3. For any significant clinical and laboratory abnormalities, the researchers believe that they affect the safety evaluators, such as: a. uncontrollable diabetes - fasting blood glucose>250 mg/dL (13.9 mmol/L), b. hypertension and cannot be reduced to the following range after treatment with two or more antihypertensive drugs (systolic blood pressure<160 mmHg, diastolic blood pressure<100 mmHg), c. peripheral neuropathy;
4. Patients with a history of congestive heart failure (NYHA grade III or above), unstable angina or myocardial infarction, cerebrovascular accidents or thromboembolism within the first 6 months of screening;
5. Individuals with impaired cardiac function (those with ejection fraction<45% detected by echocardiography, congenital ventricular arrhythmia, QTcF>450 ms on electrocardiogram (males), QTcF>470 ms on electrocardiogram (females), or those with arrhythmia requiring treatment at the time of screening);
6. Patients with congenital or acquired bleeding disorders or unstable thrombotic diseases requiring anticoagulant therapy;
7. Any active infection requiring systemic treatment (oral, intravenous, subcutaneous, intramuscular, etc.) within the first 14 days of randomization;
8. Active infection of hepatitis B virus (HBV) or hepatitis C virus (HCV), except for the following patients: a) HBV infection: patients who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and undergo peripheral blood HBV-DNA testing, with the lower limit of HBV-DNA detection value (i.e. the upper limit of normal value in the laboratory of each research center) can be enrolled; If the baseline HBsAg is positive, continuous antiviral treatment is required after enrollment, and HBV-DNA testing should be conducted every 12 weeks and at EOT visits; b) Patients who are positive for HCV serology but negative for HCV-RNA can be included in the study;
9. Patients who are positive for human immunodeficiency virus antibodies (HIV Ab) or anti Treponema pallidum antibodies (TP Ab) (Treponema pallidum antibodies positive);
10. Patients with epilepsy or those taking psychotropic or sedative drugs during screening;
11. Pregnant or lactating female patients, female/male patients with fertility who refuse to use contraceptive measures during the trial period and within 6 months after the trial ends;
12. Patients who have suffered from other malignant tumors within the past 5 years before the first administration (excluding cured carcinoma in situ and basal cell carcinoma of the skin);
13. Patients with combined swallowing difficulties;
14. Patients who participated in clinical trials of other new drugs or medical devices within the first month of randomization and took the study drug or used the study device;
15. Researchers believe that there are other factors that are not suitable for participating in the experiment.