Sibenik

Researchers are studying whether adding navtemadlin to ruxolitinib treatment can provide more benefit than ruxolitinib alone for adults with Myelofibrosis who have not responded well to ruxolitinib by itself. This Phase 3 trial includes patients who are new to JAK inhibitor treatment and have a confirmed diagnosis of primary or post-polycythemia vera or post-essential thrombocythemia Myelofibrosis. The study aims to assess improvements in spleen size and symptom reduction over 24 weeks, as well as long-term outcomes like disease progression and overall survival. Participants first receive ruxolitinib alone during a run-in period to identify those with suboptimal response. Those qualifying are randomly assigned in a 21 ratio to receive either navtemadlin or a placebo as an add-on to their ongoing ruxolitinib. Navtemadlin or placebo is taken orally once daily for 7 days followed by 21 days off in 28-day cycles, while ruxolitinib is taken twice daily continuously. The study is double-blinded so neither participants nor researchers know which add-on treatment is given. During the trial, participants will undergo evaluations including spleen volume measurements and symptom assessments at 24 weeks. They will be monitored for disease progression and survival for up to 8 years. The study includes regular check-ups to track side effects, treatment adherence, and overall health status. These detailed assessments help researchers understand the potential benefits and safety of adding navtemadlin for patients with Myelofibrosis.

Researchers are evaluating the efficacy and safety of givinostat compared to hydroxyurea in patients with high-risk polycythemia vera PV who have the JAK2V617F mutation. PV is a chronic blood disorder that increases the risk of blood clots, progression to myelofibrosis, and transformation into acute leukemia. Patients aged 60 or older or those with a prior thrombotic event are considered high risk. Current treatments with hydroxyurea often do not fully control symptoms or long-term risks. Participants will be randomly assigned to receive either oral givinostat at 50 mg twice daily or hydroxyurea at 500 mg twice daily for 48 weeks. Dosages may be adjusted based on side effects or lack of effectiveness. After this core treatment phase, eligible patients can enter an extended treatment phase to receive long-term givinostat, allowing collection of additional safety and efficacy data. Throughout the study, participants will have regular visits to monitor blood counts, spleen size, and treatment responses. Researchers will assess the proportion of patients achieving a response at week 48, including complete hematological response and spleen size normalization. Safety and tolerability will be evaluated up to week 48. The study aims to collect comprehensive data on treatment effects and patient outcomes over time.