Jaktinib for the Treatment of Ruxolitinib Intolerance of Myelofibrosis

Inclusion Criteria: 1. Age 18-75 years old (including the threshold value), gender is not limited; 2. Subjects diagnosed with Primary Myelofibrosis according to World Health Organization (WHO) criteria (2016 version), or diagnosed with Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis according to International Working Group Myeloproliferative Neoplasms Research and Treatment(IWG-MRT) standard. Both Janus Kinase 2(JAK2)mutation and JAK2 wild can be enrolled； 3. According to Dynamic International Prognostic Scoring System(DIPSS) , Subjects with intermediate-risk-2 or high-risk myelofibrosis were assessed, Subjects with intermediate-risk-1 myelofibrosis with hepatosplenomegaly and no response to existing treatment and requiring treatment can also be enrolled; 4. Subjects who have received or are receiving Ruxolitinib, and：Ruxolitinib treatment time is not less than 28 days; Red blood cell transfusion is still needed during treatment with Ruxolitinib; or Ruxolitinib dose (including starting dose and adjusted dose)\<20mg bid，And must meet at least one of the following：Level 3 or higher platelet count reduction or Level 3 or higher anemia or Level 3 or higher hematoma/bleeding； 5. Life expectancy \> 24 weeks; 6. Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0, 1 or 2； 7. Splenomegaly: palpation of the splenic margin to or above the subcostal at least 5cm； 8. Acceptable laboratory assessments obtained within 14 days prior to enrollment: * Absolute neutrophil count(ANC)\>0.75 x 10\^9/L, blood platelet count\>100 x 10\^9/L; * Peripheral blood blast count \< 10%; * Aspartate transaminase (AST) and alanine transaminase (ALT)≤3 x the upper limit of the normal range (ULN); Subjects with liver function impairment due to severe extramedullary haematopoiesis or iron removal therapy within 60 days prior to screening, AST and ALT≤5 x ULN; Direct bilirubin≤2.0 x ULN; * Calculated creatinine clearance of≥45 mL/min； 9. Meet the requirements of the Ethics Committee, voluntarily sign an informed consent form； 10. Ability to follow research and follow-up procedures. Exclusion Criteria: 1. Any significant clinical or laboratory abnormalities that the investigator considers to affect safety assessment, such as: a. uncontrolled diabetes (\> 250 mg/dL, or 13.9\>mmol/L); b. had high blood pressure and antihypertensive drug treatment under two or unable to descend to the ranges (systolic blood pressure \< 160 mmHg, diastolic pressure \< 100 mmHg); c. peripheral neuropathy (NCI-CTC AE v5.0 grade 2 or above), etc; 2. Subjects who had a history of congestive heart failure(NCI-CTC AE v5.0 grade 3 or above), uncontrollable or unstable angina or myocardial infarction, cerebrovascular accident or pulmonary embolism in the first 6 months; 3. Screening of Subjects who have surgery within the first 4 weeks; 4. Screening for Subjects with arrhythmia requiring treatment or QTc interval (QTcB) \>480ms; 5. Screening for bacterial, viral, parasitic or fungal infections that require treatment; 6. Patients which have with a history of congenital or acquired hemorrhagic diseases;(Note:With the exception of hematoma which caused by Ruxolitinib) 7. Splenectomy Subjects or in the group carried out within three months before the spleen radiation treatment (including internal radiation and external radiation) 8. Screening HIV, HBV DNA positive or higher than the normal reference range, or HCV RNA positive for HCV antibody; 9. Women who are planning to become pregnant or who are pregnant or breast- feeding, as well as those who were unable to use effective contraceptives throughout the trial;Male patients who do not use condoms during the administration and within 2 days (approximately 5 half-lives) after the last administration; 10. Subjects who have suffered from malignant tumors (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years; Combined with other serious diseases, the researchers believe that patients' safety or compliance may be affected; 11. With other serious diseases, the researchers think that may affect patient safety or compliance; 12. Subjects who had used the Jaktinib; 13. Subjects who have participated in the clinical trials of other new drugs or medical devices within the first 1 months; 14. Subjects who used the Hematopoietic growth factors within 14 days before Into the group (granulocyte growth factors, or platelet hormone) ； 15. Subjects who cannot cooperate with or cannot perform MRI or CT scans； 16. Subjects with refractory or recurrent myelofibrosis: refractory of myelofibrosis:After at least 28 days of adequate administration of JAK inhibitors, the spleen palpation was less than 15% smaller than before administration.Or at least 3 months later, the spleen volume on MRI/CT decreased by \<10% compared with that before the administration. Recurrence of myelofibrosis: after at least 3 months of taking adequate amount of JAK inhibitor, the spleen was enlarged again after shrinking compared with that before taking the drug, and compared with the minimum value during taking the drug, the spleen volume increased ≥10% on MRI/CT examination or ≥30% on spleen palpation. 17. Any treatment MF medication (eg hydroxyurea,except ruxolitinib ), any immunomodulation used within 2 weeks prior to enrollment Agent (such as thalidomide), any immunosuppressant, glucocorticoids ≥ 10 mg/day of prednisone or equivalent biological strength, or Subjects within 6 half-life of the drug, over time Prevail; Subjects who had received Ruxolitinib within 1 week prior to enrolling.