Sibenik

Researchers are evaluating whether adding navtemadlin to ruxolitinib treatment provides more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have not responded well to ruxolitinib alone. This Phase 3, randomized, double-blind study focuses on patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis. Participants must be JAK inhibitor-naive and have a suboptimal response to ruxolitinib treatment during the initial run-in period. During the study, all subjects start by receiving ruxolitinib alone in a run-in period. Those showing a suboptimal response are then randomly assigned in a 2:1 ratio to receive either navtemadlin or a navtemadlin placebo as an add-on to their ongoing ruxolitinib treatment. The study is blinded, so neither the participants nor the doctors know who is receiving the navtemadlin or placebo. Navtemadlin is an investigational MDM2 inhibitor, while ruxolitinib is a janus kinase 1/2 inhibitor. Participants are involved in assessments to compare spleen volume reduction and total symptom score reduction between the two treatment groups over 24 weeks. Researchers monitor safety and efficacy through clinical evaluations, symptom tracking, and laboratory tests. The study includes screening for performance status, blast counts, and TP53 wild-type status, ensuring participants meet specific health criteria before randomization.

Researchers are evaluating the effectiveness and safety of givinostat compared to hydroxyurea in patients with high-risk polycythemia vera (PV) who have the JAK2V617F mutation. PV is a chronic condition that increases the risk of blood clots and can progress to more severe diseases like myelofibrosis or leukemia. High-risk patients are those aged 60 or older or those with a history of blood clots. Current treatments often do not fully control symptoms or long-term risks in these patients. The study involves two treatment groups receiving oral medications: givinostat or hydroxyurea. Dosages of both drugs are adjusted based on side effects or how well the treatment is working, aiming for an optimal dose. The core treatment phase is a pivotal phase 3 trial designed to show whether givinostat is more effective than hydroxyurea. Patients who finish this phase may continue receiving givinostat in an extended treatment phase to collect additional long-term safety and efficacy data. Participants will be assessed regularly, including monitoring blood counts and clinical response up to week 48. The main outcome measured is the proportion of patients who achieve a response by week 48, evaluated between weeks 25 and 48. Safety monitoring includes heart rhythm checks and other clinical evaluations. Eligible patients must meet specific criteria related to diagnosis, risk factors, and treatment needs, and those who complete the core phase successfully may enter the extended phase for further observation.