The goal of this clinical trial is to compare the efficacy and safety of givinostat to hydroxyurea in Jak2V617F-positive high risk polycythemia vera patients.
PV is a cMPN mainly driven by JAK2V617F mutation. The disease has an increased risk of thromboembolic complications, a predisposition to evolve into myelofibrosis (MF) and transformation into acute myeloid leukemia. Patients ≥ 60 years of age and/or with a previous thrombotic event (TE) are considered at High Risk (HR) for thrombosis. The association of absolute values of circulating neutrophil, lymphocyte and monocyte and the high value of JAK2V617F allele burden are additional risk factors for the occurrence of thrombosis and for progression to MF, respectively. Overall, most patients treated with HU are not adequately under control for both symptoms and long-term risks. In recent years, data have shown that histone deacetylase (HDACs) inhibitors induce growth arrest, differentiation, and/or apoptosis in neoplastic cells. Givinostat has demonstrated preliminary signs of clinical activity and an acceptable safety profile in patients with JAK2V617F-positive cMPNs in three phase 2 studies. The core treatment phase (pivotal phase 3 study) is designed to demonstrate the superiority of givinostat versus HU on efficacy, in JAK2V617F-positive, HR PV patients. The extended treatment phase will allow eligible patients to receive givinostat in the long-term, with the objective of collecting long-term safety and efficacy data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
220
Oral. The dosage must be modified, according to the manifestation of toxicities or lack of efficacy, with the aim to achieve an optimized dose.
Oral. The dosage must be modified, according to the manifestation of toxicities or lack of efficacy, with the aim to achieve an optimized dose.
Proportion of patients achieving a response at Week 48.
Response assessment based on: * Hematocrit \< 45% without phlebotomy in the prior 3 months, and * White blood cell (WBC) count ≤ 10 × 109/L, and * Platelet count ≤ 400 × 109/L, and * Normal spleen size as measured by imaging (normal spleen size is defined as: a longitudinal diameter ≤ 12 cm for female and ≤ 13 cm for male) and * During Part 2 (Week 25 to 48), absence of progressive disease, major hemorrhagic events and major thrombotic events.
Time frame: week 25 - week 48
Proportion of patients achieving a complete hematological response (CHR) at Week 48.
CHR based on: * Hematocrit \< 45% without phlebotomy in the prior 3 months, and * White blood cell (WBC) count ≤ 10 × 109/L, and * Platelet count ≤ 400 × 109/L
Time frame: week 48
Time from randomization to the first observed CHR
Time frame: Randomization - week 48
Proportion of patients with a normal spleen size at Week 48.
Time frame: week 48
Safety and tolerability up to Week 48.
Time frame: Randomization - week 48
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University of Alabama at Birmingham
Birmingham, Alabama, United States
NOT_YET_RECRUITINGEmad Ibrahim, MD, Inc
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