Safety of Flonoltinib Maleate Tablets for the Treatment of Patients With Myeloproliferative

Inclusion Criteria:

1. Age ≥18, gender unlimited;

2. Patients diagnosed as PMF, PV (PV at least 24 weeks), ET according to WHO criteria (2016 edition), or post-PV-MF or post-ET-MF according to IWG-MRT criteria;

3. Any of the following criteria is met :(1) Patients receiving treatment for myeloidfibrosis must be at least medium-risk -1 or high risk as assessed according to theDIPSS risk grouping criteria; (2) PV and ET patients who are resistant or intolerantto hydroxyurea and/or interferon therapy;

4. No immediate plans for a stem cell transplant;

5. At least 4 weeks or more than 5 half-lives (whichever is longer) after receiving thelast antitumor therapy (chemotherapy, radiotherapy, biotherapy or immunotherapy)before enrollment;

6. Expected survival ≥12 weeks;

7. ECOG≤2;

8. Splenomegaly: palpate the margin of the spleen (the farthest point of the spleen) atleast 5 cm below the costal margin; Or not accessible due to body type (obesity),but confirmed by MRI (CT scan if necessary) spleen assessment at screening time, thevolume is ≥450 cm3;

9. Bone marrow primitive cells and peripheral blood primitive cells ≤10%;

10. PLT≥75×109 /L, ANC≥1.0×109 /μL, HGB> without the assistance of colony stimulatingfactor, growth factor, thrombogenic factor or platelet infusion; 80 g/L. Subjectsdid not receive growth factor, colony-stimulating factor, thrombogenic factor orplatelet transfusions within 2 weeks before examination.

11. Heart, lung, liver, kidney, pancreas without serious organic lesions (LVEF (leftventricular ejection fraction) ≥45%; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN or CCR> 40 ml/min. Alanine aminotransferase (ALT) ≤2×ULN; Aspartateaminotransferase (AST) ≤2×ULN;

12. No severe coagulation abnormalities (PT≤1.5×ULN, APTT≤1.5×ULN, TT≤1.5×ULN);

13. Those who agree to participate in the study and sign the informed consent;

14. Agree to comply with the regulations of the hospital and research institution.

Exclusion Criteria:

1. The toxicity of previous anticancer therapy does not recover to grade I or below (except for hair loss), or does not fully recover from previous surgery (majorsurgery within 4 weeks);

2. Allergic constitution, allergy to test drugs and their excipients;

3. Any significant clinical or laboratory abnormalities that the investigator considersto affect the safety reviewer, such as: A. Uncontrolled diabetes - fasting glucose > 250 mg/dL (13.9 mmol/L), b. Patients with hypertension who cannot be reduced to thefollowing range after treatment with two or less antihypertensive drugs (systolicblood pressure < 160 mmHg, diastolic blood pressure < 100 mmHg), c. Peripheralneuropathy (NCI-CTC AE V5.0 Grade 2 or above);

4. Patients with a history of congestive heart failure, unstable angina pectoris ormyocardial infarction, cerebrovascular accidents, or pulmonary embolism within thefirst 6 months were screened;

5. Patients with impaired heart function (Ejection fraction measured by ultrasonicelectrocardiogram; ST segment descending in two or more channels in 45% or completeleft bundle branch block > 1 mm or T wave inverted; Congenital ventriculararrhythmia, clinically significant tachycardia (>; 100 beats/min), bradycardia (lt; 50 times/min), ECG QTc > 450 ms (male), QTc > 480 MS (female) or clinicallysignificant heart disease (such as unstable angina pectoris, congestive heartfailure, myocardial infarction within 6 months);

6. Arrhythmic disease requiring treatment, or QTC interphase (QTCB) > 480 ms;

7. Any active infections requiring treatment at the time of screening;

8. Patients who had previously undergone splenectomy or who had received radiotherapyin the splenic region within 12 months prior to screening;

9. Positive HIV antibody, positive active hepatitis B virus (HBsAg positive, HBV-DNApositive or ≥1000 copies/mL), positive anti-HCV antibody or HCV-RNA at screeningtime;

10. Screening patients with epilepsy or using psychotropic drugs or sedatives;

11. Pregnant or lactating women, fertile women/men who refuse to use contraceptivesduring the trial and within 6 months after the trial;

12. Patients who have had malignant tumors (except cured basal cell carcinoma of theskin and carcinoma in situ of the cervix) in the past 5 years;

13. Concomitant with other serious diseases that the investigator believes may affectpatient safety or compliance;

14. Screening patients who participated in other new drugs or medical devices and tookstudy drugs or used study devices within the previous 1 months;

15. Within 2 weeks before randomization and into the group to use any drug for MF (JAKinhibitor, hydroxyurea), any immune modulators (such as Sally degree amine), anyimmune inhibitors, 10 mg/day or prednisone or equivalent strength of biologicaleffect of glucocorticoid, growth factors, such as EPO therapy, or within six drughalf-life of patients;

16. Intravenous use of either a potent or moderate CYP3A inhibitor (such asketoconazole, clarithromycin, itraconazole, nefazoldone, telimycin) or a potentCYP3A4 inducer (rifampicin perforatum) within two weeks prior to initialadministration;

17. Patients with a history of congenital or acquired bleeding diseases;

18. Alcohol dependence or drug abuse;

19. People who use grapefruit, star fruit or its products within 48 hours before takingthe study drug for the first time, or who do not agree to prohibit the consumptionof the above-mentioned food, drink or other special diet, which may affect theabsorption, distribution, metabolism and excretion of the study drug;

20. Other factors considered by the investigator to be unsuitable for participation inthe study.