Abdulraheem Yacoub, MD from the University of Kansas Center for Bioinformatics speaks about the ASH 2021 Abstract – 2579 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ruxolitinib Plus Parsaclisib in Patients with JAK- and PI3K-Inhibitor Treatment"“Naive Myelofibrosis.
Link to Abstract:
https://ash.confex.com/ash/2021/webprogram/Paper148794.html
Background:
Ruxolitinib is a Janus kinase (JAK)1/JAK2 inhibitor that improves myelofibrosis patient outcomes dramatically (MF). However, ruxolitinib alone may have an unsatisfactory response in some patients; deeper and longer-lasting responses in these patients could be achieved by combining ruxolitinib with medicines that target other signaling pathways involved in MF development. According to recent phase 2 results, adding the phosphatidylinositol 3 kinase (PI3K) inhibitor parsaclisib to ruxolitinib monotherapy resulted in additional relief of MF symptoms and splenomegaly in patients with MF (Yacoub A. EHA2021. PB1716).
Aims:
This phase 3 randomized, double-blind research (INCB 50465-313, NCT04551066) looks at the combination of ruxolitinib and parsaclisib in MF patients who haven’t had success with JAK and PI3K inhibitors.
Methods:
Patients must be at least 18 years old, have a diagnosis of primary MF, post"“polycythemia vera MF, or post"“essential thrombocythemia MF, have a Dynamic International Prognostic Scoring System (DIPSS; Passamonti F. Blood. 2010;115:1703"“8) risk of at least intermediate (INT)-1, a palpable spleen 5 cm below the left subcostal margin, a Patients who have previously received any JAK inhibitor, any PI3K inhibitor, any experimental or standard drug therapy for MF within 3 months of the first study dose, have a recent history of inadequate bone marrow reserve (eg, platelet count 50109/L), or have inadequate liver or renal function at screening will be excluded. Approximately 440 patients will be randomized (1:1) to receive ruxolitinib plus parsaclisib 5 mg once daily or ruxolitinib plus 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 (Figure 1). Treatment will begin on day one, with a beginning ruxolitinib dose decided by baseline platelet count, and will last as long as the patient tolerates it and the discontinuation criteria are not satisfied. The research will be unblinded when the final enrolled patient has completed 24 weeks of treatment, and individuals randomized to ruxolitinib with placebo who have satisfactory hematological parameters will be able to switch to parsaclisib with ongoing ruxolitinib. The primary goal is to assess and compare spleen volume in individuals who got ruxolitinib plus parsaclisib vs. ruxolitinib plus placebo at week 24. Evaluation and comparison of patient-reported MF symptoms, overall survival, time to onset and duration of spleen volume response, and safety and tolerability of ruxolitinib plus parsaclisib vs ruxolitinib plus placebo are secondary objectives. Sites can be found all over the world, including the United States, Europe, the United Kingdom, and Asia.