Clinical trial NCT01445769
Conditions: Primary Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis
Keywords: Myelofibrosis Primary Myelofibrosis PMF Post-Polycythemia Vera Myelofibrosis PPV-MF Post-Essential Thrombocythemia Myelofibrosis PET-MF Open label Ruxolitinib 18424 Jak inhibitor
Sponsor: Incyte Corporation
Start date: 2011-09-01; Completion date: 2013-04-01
Enrollment: 45 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed description:
This pilot study was designed to explore an alternative dosing approach with the purpose of reducing anemia and thrombocytopenia. Subjects began dosing at 10 mg bid and had the opportunity for dose increases based on assessments of efficacy and overall hematologic status in a defined prior dosing interval. Dose increases were restricted to those patients who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10\^9/L at week 12 or ≥150 x 10\^9/L at week 18, and had a self-reported Patient's Global Impression of Change (PGIC) score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length below the costal margin had been reduced by less than 40% at that visit 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 Week 12 and to a maximum of 20 mg BID at Week 18. There were also 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).This approach assumed that beginning at a low dose for initial therapy might have a positive impact on the rate of the initial hemoglobin decline and the nadir by decreasing the level of JAK-mediated inhibition of hematopoiesis. Specific dose modifications were described to minimize excursions of hemoglobin levels into the Grade 3 or Grade 4 range.

Arms: arm 1: Participants initially received ruxolitinib 10 mg twice a day (bid) for 24 weeks. Dose increases of 5 mg bid were possible at Weeks 12 and 18 up to a maximum dose of 20 mg bid.
Interventions: intervention 1: Ruxolitinib
Intervention descriptions: intervention 1: 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).

Protocol documents: