Alternative Dosing Strategy of Ruxolitinib in Patients With Myelofibrosis
Condition: Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis
MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: Ruxolitinib
Intervention description: Ruxolitinib was provided as 5 mg tablets. Dose increases were only permitted at wks 12 & 18 for lack of efficacy. Increases were restricted to patients who didn't meet criteria for a dose hold over the prior 6 wks, had a platelet count ≥ 100 x 10^9/L at wk 12 or ≥ 150 x 10^9/L at wk 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length below the costal margin was reduced by less than 40% relative to Baseline. Dose increases were elective and not required. Subjects were permitted a dose increase of 5 mg BID to 15 mg BID at wk 12 and to a maximum of 20 mg BID at wk 18. The protocol required dose decreases for thrombocytopenia (platelets <100 x 10^9/L) or protocol-defined anemia (decline in hemoglobin of at least 2 g/dL to a level < 8 g/dL, development of transfusion dependence, or a 50% increase in transfusion requirements for transfusion dependent subjects).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myelofibrosis; Primary Myelofibrosis; PMF; Post-Polycythemia Vera Myelofibrosis; PPV-MF; Post-Essential Thrombocythemia Myelofibrosis; PET-MF; Open label; Ruxolitinib; 18424; Jak inhibitor

Summary:

      The purpose of this study was to evaluate the effect of an alternative dosing strategy of
      ruxolitinib in subjects with primary myelofibrosis (PMF), post-polycythemia
      vera-myelofibrosis (PPV-MF) and post essential thrombocythemia-myelofibrosis (PET-MF) in
      order to minimize the development of anemia and thrombocytopenia.
    

Eligibility criteria:

        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 Dynamic International Prognostic Scoring System
             (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 myelofibrosis (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*10^9/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.