A Clinical Study of Ruxolitinib in Patients With Primary Myelofibrosis (PM), Post-polycythemia Vera (PV) Myelofibrosis, or Post-essential Thrombocythemia (ET) Myelofibrosis
Condition: Primary Myelofibrosis (MF)
MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: Ruxolitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Post-Polycythemia Vera (PV) MF; Post-Essential Thrombocythemia (ET) MF

Summary:

      This is an open-label, multicenter clinical study in order to collect and examine data
      concerning the safety and efficacy of ruxolitinib in patients with Primary Myelofibrosis
      (MF), Post-Polycythemia Vera (PV) MF, Post-Essential Thrombocythemia (ET) MF.
    

Eligibility criteria:

        Inclusion Criteria:

          1. ≥18 years of age

          2. 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).

          3. 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)

          4. 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.

          5. Proportion of blasts in peripheral blood <10%

          6. ECOG performance status of 0 to 2

          7. The following values for bone marrow function prior to treatment:

               1. Absolute neutrophil count ≥1,000/μL, and

               2. Platelet count ≥50,000/μL without administration of a growth factor,
                  thrombopoietin, or platelet transfusion

          8. Stem cell transplantation is not a treatment option at present because it is not
             indicated or because there are no suitable donors.

          9. All drugs used to treat MF were discontinued at least 28 days before treatment
             initiation.

         10. Informed consent form should be signed before any screening procedures is performed

        Exclusion Criteria:

          1. 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

          2. 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)

          3. 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.

          4. History of malignancy within the previous 3 years, except for early-stage squamous
             cell carcinoma and basal cell carcinoma.

          5. History of serious congenital or acquired hemorrhagic disease

          6. 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.

          7. Splenic irradiation within 12 months before screening

          8. 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.

          9. Currently receiving another investigational drug, or received another investigational
             drug within 30 days before the start of treatment.

         10. History of myocardial infarction or acute coronary syndrome within 6 months before
             screening

         11. Poorly controlled or unstable angina at present

         12. Rapid or paroxysmal atrial fibrillation at present

         13. Active alcohol or drug addiction that could hinder the patient's ability to comply
             with the study's requirements

         14. Pregnant or currently breastfeeding woman

         15. Women of childbearing potential or men with reproductive ability who are unwilling to
             take appropriate contraception measures

         16. Patient with any concurrent condition that, in the Investigator's opinion, would
             jeopardize the safety of the patient or compliance with the protocol

         17. History of hypersensitivity to the study drug or a drug with a similar chemical
             structure