Alternative Dosing Strategy of Ruxolitinib in Patients With Myelofibrosis

• Assessment of safety and tolerability [ Time Frame: At each study visit up to 24 weeks. ] [ Designated as safety issue: Yes ]
  Monitor frequency, duration and severity of adverse events, perform physical examinations, collect vital signs and clinical laboratory data.
• Mean % change in Total Symptom Score as measured by the modified MFSAF v2.0 diary at Week 24 compared to Baseline [ Time Frame: Baseline and Week 24 study visits ] [ Designated as safety issue: No ]
• Proportion of subjects with ≥ 35% reduction in spleen volume at Week 24 compared to Baseline [ Time Frame: Baseline and Week 24 study visits ] [ Designated as safety issue: No ]

To evaluate the effect of an alternative dosing strategy of ruxolitinib on spleen volume in subjects with primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) and post essential thrombocythemia-myelofibrosis (PET-MF).

This study is designed to explore a new dosing approach. Subjects will begin dosing at 10 mg bid and will have opportunity for dose increases based on assessment of efficacy and overall anemia status in a defined prior dosing interval. The dose may be increased up to a maximum dose of 20 mg bid. This approach assumes that beginning at a low dose for initial therapy may impact the rate of the initial hemoglobin decline and the nadir, by decreasing the level of JAK-mediated inhibition of hematopoiesis. Specific dose modifications are described to minimize excursions of hemoglobin levels into the Grade 3 or Grade 4 range.

• Primary Myelofibrosis
• Polycythemia Vera, Post-Polycythemic Myelofibrosis

Inclusion Criteria:

• Diagnosis of Primary Myelofibrosis (PMF), Post Polycythemia Vera Myelofibrosis (PPV-MF), or Post Essential Thrombocythemia Myelofibrosis (PET-MF) as confirmed by bone marrow biopsy.
• Must score at least 2 points on the DIPSS scale for prognostic risk factors
• Peripheral blast count < 5% at both Screening and Baseline hematology assessments.
• Must discontinue all drugs used to treat underlying MF disease no later than Day -1 (the day prior to starting ruxolitinib).
• Must have hemoglobin value ≥ 6.5 g/dL and be willing to receive blood transfusions.
• Platelet count ≥ 100 x10^9/L.
• Must have a palpable spleen.

Exclusion Criteria:

• Inadequate liver or bone marrow reserves, end stage renal disease on dialysis, clinically significant concurrent infections requiring therapy, or unstable cardiac function.
• Invasive malignancies over the previous 5 years (except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix and completely resected papillary thyroid and follicular thyroid cancers.)
• Splenic irradiation within 6 months prior to receiving the first dose of study medication.
• Life expectancy less than 6 months.