bone marrow proliferative tumors
Conditions
Interventions
Group 1:25mg flunotinib maleate tablets
Group 2:50mg flunotinib maleate tablets
Group 3:100mg flunotinib maleate tablets
Group 4:150mg flunotinib maleate tablets
Group 5:225mg flunotinib maleate tablets
Group 6:325mg flunotinib maleate tablets
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >= 18 years, gender is not limited; 2. Patients diagnosed with PMF, PV (diagnosed with PV for 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 conditions are met: (1) Treated patients with myelofibrosis who must be at least intermediate-1 or high-risk according to the DIPSS risk grouping criteria; (2) PV and ET patients who are resistant or intolerant to hydroxyurea and/or interferon therapy; 4. There is no recent stem cell transplant plan; 5. Before enrollment, patients received at least 4 weeks or more than 5 half-lives (whichever is longer) after the last antitumor treatment (chemotherapy, radiotherapy, biological therapy or immunotherapy); 6. Expected survival time >= 12 weeks; 7. ECOG score=450 cm^3; 9. Bone marrow blast cells and peripheral blood blast cells=75x10^9/L and ANC>=1.0x10^9/µL, HGB>80 g/L without the assistance of colony stimulating factor, growth factor, thrombopoietic factor or platelet transfusion. The patients did not receive growth factors, colony-stimulating factors, platelet production factors and platelet transfusions within 2 weeks before the examination; 11. Patients without serious organic lesions in the heart, lung, liver, kidney and pancreas (LVEF (left ventricular ejection fraction) >=45%; total bilirubin 40 mL/min; alanine aminotransferase (ALT)<=2xULN; aspartate aminotransferase (AST)<=2xULN; 12. Those without severe coagulation dysfunction (PT<=1.5xULN, APTT<=1.5xULN, TT<=1.5xULN); 13. Those who agree to participate in this study and sign the informed consent; 14. Agree to abide by the relevant regulations of hospitals and research institutions.
Exclusion criteria
Exclusion criteria: 1. The toxicity of previous anticancer therapy has not recovered to grade I or below (except for hair loss), or has not fully recovered from previous surgery (major surgery within 4 weeks); 2. Allergic constitution, allergy to the test drug and its excipients; 3. Any significant clinical and laboratory abnormalities that the investigator considers affecting the safety assessor, such as: (1) Uncontrolled diabetes - fasting blood glucose > 250 mg/dL (13.9 mmol/L); (2) Those with hypertension who cannot be reduced to the following range after two or less antihypertensive drugs (systolic blood pressure 1 mm or T wave inversion in two or more channels; Congenital ventricular arrhythmia, clinically significant tachycardia (>100 beats/min), bradycardia (450 ms (men), QTc >480 ms (women) or clinically significant heart disease (such as unstable angina, congestive heart failure, myocardial infarction within 6 months), etc.; 6. Patients with arrhythmia disease requiring treatment at screening, or patients with QTc interval (QTcB) > 480 ms; 7. Any active infection requiring treatment at the time of screening; 8. Patients who have undergone splenectomy in the past or patients who have received radiation therapy to the spleen area within 12 months before screening; 9. HIV antibody positive at screening, positive for active hepatitis B virus detection (HBsAg positive, HBV-DNA positive or >=1000 copies/mL), anti-HCV antibody or HCV-RNA positive; 10. Patients with epilepsy or using psychotropic or sedative drugs at screening; 11. Pregnant or lactating patients, patients with reproductive potential who refuse to use contraceptive measures during the trial and within 6 months after the trial; 12. Patients who have suffered from malignant tumors in the past 5 years (except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix); 13. Patients with other serious diseases, which the researchers believe may affect the safety or compliance of patients; 14. Patients who participated in other new drugs or medical devices within 3 months before screening and took research drugs and used research devices; 15. Have used any MF drug (such as JAK inhibitor, hydroxyurea), any immunomodulator (such as thalidomide), any immunosuppressant, >=10 mg/day prednisone or glucocorticoids of equivalent biological potency, growth factors (such as EPO) treatment, or patients within 6 half-lives of the drug; 16. Have taken a strong or moderate CYP3A inhibitor (such as ketoconazole, clarithromycin, itraconazole, nefazodone, telithromycin) within two weeks before the first dose or potent CYP3A4 inducers (rifampicin and Hypericum perforatum); 17. Patients with a history of congenital or acquired bleeding disorders; 18. Alcohol dependence or drug abusers; 19. Those who use grapefruit, star fruit or their products within 48 hours before taking the study drug for the first time, or those who do not agree to be prohibited from eating the above-mentioned foods, beverag
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| dose limiting toxicity;maximum tolerated dose;health checkup;ECG;ultrasonic cardiogram;blood routine examination;blood biochemistry (including hepatorenal pancreas function);electrolyte;coagulation function;routine urine test;adverse event; | — |
Secondary
| Measure | Time frame |
|---|---|
| peripheral blood cell count;serum EPO level;the length of the spleen;spleen volume;blood cell compaction ;total symptom evaluation scale of bone marrow proliferative tumors ; | — |
Countries
China
Contacts
Public ContactNiu Ting, Wang Yongsheng
West China Hospital, Sichuan University
Outcome results
None listed