FEDR-MF-002 (FREEDOM 2) (R/R)

A phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of Fedratinib compared to best available therapy in subjects with DIPSS-intermediate or high-risk primary myelofibrosis (PMF), postpolycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF) and previously treated with Ruxolitinib

Study treatments

• Arm 1: Fedratinib 400mg PO QD
• Arm 2: Best available therapy

Inclusion criteria

• Diagnosis of PMF or post-ET/-PV MF, with DIPSS risk score of intermediate-2 or high
• Previous exposure to Ruxolitinib but refractory and/or intolerant (see protocol for definitions!)
• Splenomegaly as demonstrated by spleen volume of ≥ 450 cm³ by MRI or CT and by palpable spleen measuring ≥ 5 cm below the left costal margin
• A measurable total symptoms score (≥1) as measured by the MFSAF
• ECOG ≤ 2
• Treatment-related toxicities from prior therapy resolved to grade 1 or pretreatment baseline

Exclusion criteria

• Platelet < 50 x 109/l, ANC < 1.0 x 109/l, WBC > 100 x 109/l, myeloblasts ≥ 5% in peripheral blood
• eGFR < 30 ml/min/1.73 m², amylase or lipase > 1.5x ULN, AST or ALT > 3x ULN, total bilirubin > 1.5x ULN
• Previous splenectomy
• Previous or planned hematopoietic cell transplant
• Subject on any chemotherapy, imunomodulatory drug therapy, anagrelide, immunosuppressive therapy, systemic corticosteroids > 10mg/day prednisone or equivalent. Prior exposure to Hydrea is allowed as long as it has not been administered within 14 days prior to randomization
• Subject received ruxolitinib within 14 days prior to randomization
• Previous exposure to JAK inhibitors other than ruxolitinib
• Prior history wernicke encephalopathy - Subjects with thiamine deficiency

Participating sites

• University Hospital Leuven Gasthuisberg
• AZ Sint-Jan Brugge
• CU Saint-Luc
• Jolimont
• CHU Sart Tilman Liège
• CU UCL Mont-Godinne