Myelofibrosis
Conditions
Interventions
The low-dose test group:Flonoltinib Maleate Tablet 50mg, oral administration, once daily, given on an empty stomach.
The high-dose test group:Flonoltinib Maleate Tablet 100mg, oral administration, once daily, given on an empty stomach.
Control group:Ruxolitinib Tablets (According to the instructions: For patients with platelet count between 100×10^9/L and 200×10^9/L, the recommended starting dose is 15mg twice daily
for patients with platelet count greater than 200×10^9/L, the recommended starting dose is 20mg twice daily. For patients with platelet count between 50×109/L and <100×10^9/L, the recommended maximum
Sponsors
Institute of Hematology, Chinese Academy of Medical Sciences / West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Age>=18 years, regardless of gender; 2.Diagnosis confirmed as:Primary myelofibrosis (PMF) per WHO 2016 criteria or post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) per IWG-MRT criteria; 3.Risk stratification: Intermediate-2 or high-risk myelofibrosis per Dynamic International Prognostic Scoring System (DIPSS); 4.Life expectancy >=24 weeks; 5.ECOG performance status 0-2; 6.Splenomegaly:Palpable spleen extending >=5 cm below the left costal midline,OR if non-palpable due to body habitus (e.g., obesity), spleen volume >=450 cm^3 confirmed by MRI/CT during screening; 7.Peripheral blood and bone marrow blasts=1.0×10^9/L,Platelet count >=50×10^9/L,Hemoglobin >60 g/L(No growth factors, colony-stimulating factors, thrombopoietin, or platelet transfusions within 2 weeks prior to baseline assessment); 9.Organ function within 7 days prior to first dose:ALT/AST 40 mL/min(Cockcroft-Gault formula:Male: CrCl = [(140-age) × weight (kg)] / [0.818 × Scr (µmol/L)]Female: CrCl = [(140-age) × weight (kg)× 0.85] / [0.818 × Scr (µmol/L)],PT/TT <=ULN +3 s,APTT <=ULN +10 s; 10.Voluntarily sign informed consent with full understanding.
Exclusion criteria
Exclusion criteria: 1. 1. The toxic reactions resulting from previous anti-cancer therapies have not subsided to grade 1 or lower (except for alopecia and the circumstances stipulated in Inclusion Criteria 8 and 9),or have not fully recuperated from previous surgeries (major surgeries within 4 weeks); 2. Individuals with allergic constitution and hypersensitivity to the test drug and its excipients; 3. Those who have experienced resistance or intolerance to ruxolitinib in the past; 4. Those who have used JAK inhibitors within 4 weeks prior to the first administration; 5. Any significant clinical and laboratory abnormalities that the investigators consider to affect the safety assessment, such as: (1) Uncontrollable diabetes - fasting blood glucose > 250 mg/dL (13.9 mmol/L), (2) Hypertension with no improvement within the range after treatment with two or more antihypertensive drugs (systolic blood pressure 1 mm in the electrocardiogram in two or more leads or T wave inversion; congenital ventricular arrhythmia, clinically significant tachycardia (> 100 beats/min), bradycardia ( 450 ms (in males), QTcF > 470 ms (in females), or those with arrhythmia diseases requiring treatment at the screening stage); 8. Any active infection requiring intravenous antibiotic treatment during screening; 9. Active tuberculosis infection occurred within 48 weeks prior to screening or latent tuberculosis infection indicated by relevant pulmonary tuberculosis-related tests during screening period; 10. Patients who have undergone splenectomy in the past or received radiation therapy in the splenic area within 12 months before the first administration; 11. Active infection of hepatitis B virus (HBV) or hepatitis C virus (HCV), except for the following patients: (1) For HBV infection: if hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) is positive, peripheral blood HBV-DNA detection shall be conducted. Patients with HBV-DNA detection values below the lower limit (i.e., the upper limit of the normal range of the laboratory department of each research center) can be enrolled; after enrollment, continuous antiviral treatment is required, and HBV-DNA detection shall be conducted at each 12-week visit and at the end-of-treatment visit; (2) For HCV serological positive patients, but with negative HCV RNA detection, can be enrolled; 12. Positive for Human Immunodeficiency Virus Antibody (HIV-Ab) or Treponema Pallidum Antibody (TP-Ab) (For patients with positive Treponema Pallidum Antibody, titers can be tested and the research team can make a comprehensive judgment on whether they can be enrolled); 13. Patients with epilepsy or using psychotropic drugs or sedatives at screening (Note: Excluding those for sleep aid); 14. Pregnant or lactating women patients, female/male patients with reproductive capacity d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects whose spleen volume decreased by>=35% compared to the baseline (at Week 24, assessed by the Independent Review Committee); | — |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of subjects whose spleen volume decreased by >=35% compared to the baseline (at 12Week,24Week,36Week,48 Week,assessed by the investigators);The proportion of subjects whose spleen volume decreased by >=35% compared to the baseline (at 12Week,36 Week,48Week, assessed by the Independent Review Committee);Response time of spleen: The time when the spleen volume is observed to have decreased by >=35% compared to the baseline for the first time.;The best response rate of the spleen: The proportion of subjects whose spleen volume decreased by>=35% compared to the baseline at least once;DoMSR: The time elapsed from the date when the spleen volume decreased by =35% compared to the baseline for the first time to the date when the spleen volume increased to be less than 35% smaller than the baseline.;Duration of continuous response of the spleen: The time elapsed from the date when the spleen volume decreased by >=35% compared to the baseline to the date when the spleen volume increased by =25% compared to the lowest value recorded during the trial period including the baseline.;The proportion of subjects whose total symptom scores on the MPN-SAF TSS scale decreased by >=50% (at 12weeks,24weeks,36weeks,48weeks );Total symptom score of the MPN-SAF TSS scale and the decrease value at baseline compared with each visit (each visit);The proportion of subjects whose bone marrow fibrosis grade remained stable or improved compared to the baseline level;The objective response rate (ORR = CR + PR) of the IWG-MRT consensus standard; | — |
Countries
China
Contacts
Public ContactXiao Zhijian; Niu Ting ; Miao Jia
Chinese Academy of Medical Sciences Peking Union Medical College Blood Disease Hospital (Institute of Hematology);West China Hospital of Sichuan University
Outcome results
None listed