Myelofibrosis
Conditions
Interventions
Experimental group:Flonoltinib 75mg
Control group:Ruxolitinib Phosphate Tablets
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (IHCAMS);West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Age range of 18-80 years old (including threshold), 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.Patients with myelofibrosis assessed as intermediate-2 or high-risk according to the dynamic international prognostic scoring system (DIPSS) prognostic classification criteria; 4.According to the MPN-SAF TSS scoring scale, the total score is >=10 points; 5.Expected survival period greater than 24 weeks; 6.ECOG score 0-2 points; 7.Splenomegaly: Palpation of the splenic margin reaching or exceeding 5cm below the rib (distance from the intersection of the left clavicle midline and left rib margin to the farthest point of the spleen); 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; 8.Peripheral blood and bone marrow blasts =1.0 × 10^9/L, platelet count >=100 × 10^9/L, HGB>60 g/L (no growth factor, colony stimulating factor, platelet-derived factor, or blood transfusion received within 2 weeks prior to examination); 10.Within 7 days prior to randomization, the main organ functions were generally normal, meeting the following criteria: ALT and AST 50 mL/min; INR, PT, and APTT <= 1.5 × ULN; 11.Can understand and voluntarily sign an informed consent form.
Exclusion criteria
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(such as undergoing major surgery within 4 weeks); 2.Allergy to experimental drugs and their excipients; 3.Previous use of JAK inhibitors (excluding those exposed for 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 pressure450 ms on electrocardiogram (males), QTcF>470 ms on electrocardiogram (females), or those with arrhythmia requiring treatment at the time of screening); 7.Patients with congenital or acquired bleeding disorders or unstable thrombotic diseases requiring anticoagulant therapy; 8.Any active infection requiring systemic treatment (oral, intravenous, subcutaneous, intramuscular, etc.) within the first 14 days of randomization; 9.Individuals who have experienced active tuberculosis infection within the 48 weeks prior to screening or those who have been diagnosed with latent tuberculosis infection during the screening period (those diagnosed with latent tuberculosis infection must complete preventive anti tuberculosis treatment for at least 3 months before they can be enrolled); 10.Patients who have undergone splenectomy in the past or those who have received splenic radiation therapy within the 12 months prior to their first dose; 11.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; 12.Patients who are positive for human immunodeficiency virus antibodies (HIV Ab) or anti Treponema pallidum antibodies (TP Ab) (Treponema pallidum antibodies positive); 13.Patients with epilepsy or those taking psychotropic or sedative drugs during screening; 14.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; 15.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); 16.Patients with swallowing difficulties, chronic diarrhea, or oral absorption disorders; 17.Combining
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of subjects with >=35% reduction in spleen volume from baseline; | — |
Secondary
| Measure | Time frame |
|---|---|
| Spleen response time: The time when the spleen volume is first observed to decrease by >=35% from baseline;MPN-SAF TSS Total Symptom Score and Baseline Comparison Decrease;Overall survival period;The proportion of trial participants whose spleen volume decreased by >= 35% compared to baseline ;Optimal response rate of spleen: The proportion of trial participants who have experiein spleen volume by >=35% compared to baseline;Duration of >=35% reduction in spleen volume compared to baseline (DoMSR);The proportion of trial participants whose total symptom score has decreased by >= 50% from baseline at least once on the MPN-SAF TSS scale;MPN-SAF TSS Total Symptom Score and Baseline Comparison Decrease;Progression free survival (PFS);Leukemia free survival (LFS); | — |
Countries
China
Contacts
Public ContactXiao Zhijian;Niu Ting;Miao JIa
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (IHCAMS);West China Hospital of Sichuan University
Outcome results
None listed