A Clinical Study of Ruxolitinib in Patients With Primary Myelofibrosis (PM), Post-polycythemia Vera (PV) Myelofibrosis, or Post-essential Thrombocythemia (ET) Myelofibrosis

Inclusion criteria

• ≥18 years of age
• Diagnosis of PMF, PPV-MF, or PET-MF, regardless of JAK2 mutational status. The diagnostic of PMF will be according to the World Health Organization (WHO) criteria (Thiele et al., 2008) and PPV-MF and PET-MF according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria (Barosi et al., 2008).
• At least one risk factors provided in the definition of IWG-MRT (Cervantes et al., 2009; classified as intermediate risk-1, intermediate risk-2, or high risk)
• Patients with intermediate risk-1 (patients who have only one of the IMG-MRT risk factors indicated above ) must have palpable splenomegaly with a length of ≥5 cm from the costal margin to the point of the greatest spleen protrusion.
• Proportion of blasts in peripheral blood <10%
• ECOG performance status of 0 to 2
• The following values for bone marrow function prior to treatment:

• Absolute neutrophil count ≥1,000/μL, and
• Platelet count ≥50,000/μL without administration of a growth factor, thrombopoietin, or platelet transfusion
• Stem cell transplantation is not a treatment option at present because it is not indicated or because there are no suitable donors.
• All drugs used to treat MF were discontinued at least 28 days before treatment initiation.
• Informed consent form should be signed before any screening procedures is performed

Exclusion criteria

• Hepatic or renal impairment as indicated by the following:

• Direct bilirubin ≥2-fold than the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) >2.5-fold ULN
• Creatinine >2.0 mg/dL
• Clinically significant infection by bacteria, fungus, mycobacteria, parasite, or virus (screening and enrollment postponed until completion of antibiotic treatment in patients with an acute bacterial infection that requires antibiotic use)
• Active hepatitis A, B, or C or HIV infection defined by a positive IgM-HA Ab test [hepatitis A virus antibody (immunoglobulin M [IgM])], HBs Ag test (hepatitis B surface antigen), HCV Ab test (hepatitis C virus antibody), or HIV Ab (human immunodeficiency virus antibody) at screening.
• History of malignancy within the previous 3 years, except for early-stage squamous cell carcinoma and basal cell carcinoma.
• History of serious congenital or acquired hemorrhagic disease
• Previous platelet count <25,000/μL or absolute neutrophil count <500/μL, except for patients currently undergoing treatment for a myeloproliferative neoplasm or cytotoxic therapy for any other reason.
• Splenic irradiation within 12 months before screening
• Administration of hematopoietic growth factor receptor agonists (erythropoietin, granulocyte colony stimulating factor, romiplostim, eltrombopag) within 14 days before screening or 28 days before treatment initiation.
• Currently receiving another investigational drug, or received another investigational drug within 30 days before the start of treatment.
• History of myocardial infarction or acute coronary syndrome within 6 months before screening
• Poorly controlled or unstable angina at present
• Rapid or paroxysmal atrial fibrillation at present
• Active alcohol or drug addiction that could hinder the patient's ability to comply with the study's requirements
• Pregnant or currently breastfeeding woman
• Women of childbearing potential or men with reproductive ability who are unwilling to take appropriate contraception measures
• Patient with any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
• History of hypersensitivity to the study drug or a drug with a similar chemical structure