Primary myelofibrosis, myelofibrosis after polycythemia vera, and myelofibrosis after primary thrombocytosis
Conditions
Interventions
Experimental group:Bids, po, 8mg
Experimental group:Bids, po,16mg
Experimental group:Bids, po, 24mg
Experimental group:Bids, po, 32mg
Experimental group:Bids, po, 40mg
Experimental group:Bids, po, 48mg
Experimental group:Bids, po, 20mg
Sponsors
The First Affiliated Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1) Age =18 years old, male or female; 2) Patients diagnosed with primary myelofibrosis (PMF) according to the WHO criteria (2016 edition) or MF after polycythemia vermiculata (Post-PV-MF) or MF after thrombocythemia (Post-ET-MF) according to the IWG-MRT criteria; 3) Dose escalation: According to the Dynamic International Prognostic Score System (IPSS), patients with myofibrosis who must be at moderate risk -2 or above and have received at least one treatment (with one or more factors that affect prognosis), are not responding satisfactorily to currently available treatment or are considered by the investigator to be unsuitable for the subject's current treatment; Dose expansion: Patients with myelofibrosis who must be at moderate risk -2 or above (with one or more prognostic factors), cohort A: patients with myelofibrosis who have not previously received rucotinib; Cohort B: Those who did not respond to prior treatment with rucotinib or were intolerant to rucotinib treatment: • Rucotinib treatment intolerance is defined as patients who have previously received or are currently receiving rucotinib treatment (for at least 28 days) and: (a) Red blood cell transfusion is still required during treatment with rucotinib, or b, rucotinib dose (including initial dose and adjusted dose)75g/L without the assistance of growth factor, throbopoietic factor or platelet transfusion, no blood products such as whole blood or suspended red blood cells were transfused within 4 weeks, subjects did not receive growth factor infusion within 2 weeks before randomization; 9) 7 days before randomization, major organ function was normal, that is, the following criteria were met: ALT and AST=2.5ULN; DBIL and TBIL=2.0ULN; Serum creatinine =1.5ULN and creatinine clearance =45mL/min; 10) Comply with the requirements of the Ethics Committee, voluntarily sign the informed consent; 11) Able to comply with research and follow-up procedures.
Exclusion criteria
Exclusion criteria: 1) Patients who have not fully recovered from surgery within 4 weeks prior to screening; 2) Patients who have had prior splenectomy or who have received splenic radiotherapy within 3 months prior to screening; 3) Patients suffering from epilepsy or using psychotropic drugs or sedative drugs at the time of screening; 4) Any treatment with MF, including chemotherapy, immunomodulatory therapy (e.g., thalidomide, interferon-alpha), immunosuppressive therapy (e.g., prednisone or corticosteroids greater than 10 mg/day), radiotherapy, and erythropoietin, androgen, thrombopoietin, or granulocyte colony-stimulating factor within 2 weeks prior to admission. Except if the subject has been using a stable dose of hydroxyurea for at least 4 weeks, the subject is allowed to enter the study with no more than a stable dose of hydroxyurea for blood count control and no more than 100mg of acetylsalicylic acid (aspirin) per day; 5) Patients with grade III or above congestive heart failure (NYHA classification), uncontrolled or unstable angina pectoris, or thrombotic diseases such as myocardial infarction, cerebrovascular accident, or pulmonary embolism within 6 months prior to screening; 6) Patients with arrhythmia requiring treatment at the time of screening, or QTc interval (QTcB)>480ms; 7) Screening for bacterial, viral, parasitic or fungal infections requiring treatment with any clinical symptoms; 8) Patients who have had malignant tumors (except cured skin basal cell carcinoma and cervical carcinoma in situ) within the past 5 years; 9) Patients with unresolved toxicity = grade 2 arising from previous antitumor therapy (except stable chronic toxicity that cannot be resolved, such as peripheral nerve toxicity); 10) The combination of other serious diseases, or researchers believe that the drug is not suitable for use; 11) Any significant clinical and laboratory abnormalities that the investigator believes affect safety evaluators, such as: Uncontrolled diabetes (>NCI-CTCAEv5.0 grade 2), hypertension (systolic blood pressure =150mmHg, diastolic blood pressure =100mmHg) and thyroid dysfunction (>NCI-CTCAEv5.0 grade 2) with two or less antihypertensive drugs; 12) HIV positive, active hepatitis B virus positive (HBsAg positive and HBV-DNA=1000 copies /ml), anti-HCV antibody and HCV-RNA positive at screening; 13) Suspected allergic to rucotinib or similar drugs; 14) Women who plan to become pregnant or who are pregnant or breastfeeding and who are unable to use effective contraception throughout the trial period; 15) Participants in clinical trials of other new drugs or medical devices within 3 months before enrollment;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| p-STAT3 inhibition;The proportion of subjects with a reduced spleen volume of =35% at 24 weeks accounted for all subjects; | — |
Countries
China
Contacts
Public ContactJie Jin
The First Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed