Abdulraheem Yacoub, MD from the University of Kansas Center for Bioinformatics speaks about ASCO 2021 Abstract – A phase 3, randomized, double-blind, placebo-controlled study of ruxolitinib plus parsaclisib in patients with JAK- and PI3K-inhibitor treatment-naïve myelofibrosis.
Link to Abstract:
https://meetings.asco.org/abstracts-presentations/201296
Background information:
Ruxolitinib (a JAK1/JAK2 inhibitor) improves outcomes in individuals with myelofibrosis (MF), however, a small percentage of individuals may have a poor response. The addition of the PI3K inhibitor parsaclisib to ruxolitinib monotherapy resulted in further relief of MF symptoms and splenomegaly in individuals with MF, according to recent phase 2 results (Yacoub. EHA2020. S216). This phase 3 randomized, double-blind research (INCB 50465-313; NCT04551066) assesses the combination of ruxolitinib and parsaclisib in patients with MF who have not been treated with Janus kinase (JAK) or PI3K inhibitors.
Methodologies:
Patients must be at least 18 years old and have a diagnosis of primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF, as well as a Dynamic International Prognostic Scoring System (DIPSS; Passamonti. Blood. 2010;115:1703-1708) risk category of at least Intermediate (INT)-1, palpable spleen 5 cm below left subcostal margin, total Patients will be excluded if they have previously received therapy for MF with any JAK inhibitor, any PI3K inhibitor, any experimental or standard drug therapy for MF within 3 months of the first study dose and/or have failed to recover from all previous therapy-related toxicities to grade 1, have a recent history of insufficient bone marrow reserve (eg, platelet count = 50109/L), or have inadequate liver or renal function. Approximately 440 patients will be randomized (1:1) to receive ruxolitinib plus parsaclisib 5 mg QD or ruxolitinib with matched placebo, with DIPSS risk category (high vs INT-2 vs INT-1) and platelet count (100 109/L vs 50 to = 100 109/L inclusive) stratified at randomization. Medication will begin on Day 1 with a beginning ruxolitinib dose based on the patient’s baseline platelet count and will last as long as the patient tolerates the treatment and the discontinuation criteria are not reached. The research will be unblinded when the final recruited patient has completed 24 weeks of therapy, and individuals assigned to ruxolitinib with placebo who have satisfactory hematological parameters will be eligible to switch to parsaclisib with ongoing ruxolitinib. The primary goal is to assess and compare spleen volume in individuals who got ruxolitinib plus parsaclisib against ruxolitinib plus placebo at Week 24. Secondary goals include comparing ruxolitinib plus parsaclisib to ruxolitinib plus placebo in terms of patient-reported MF symptoms, overall survival, time to onset and duration of spleen volume response, and safety and tolerability. Sites are springing up all around the world, including the United States, Europe, Asia, and New Zealand. NCT04551066 is the number for the clinical study.