A phase 3 trial being conducted across the United States, Europe, and Asia will investigate the safety and efficacy of parsaclisib and ruxolitinib vs placebo and ruxolitinib among patients with myelofibrosis who have displayed a suboptimal response to ruxolitinib only. The study’s design and aims were presented in a poster at the British Society of Haematology 61st Annual Scientific Meeting.

Myelofibrosis is a rare myeloproliferative disease with heterogeneous presentation. The neoplasm is associated with reduced health-related quality of life, reduced survival, bone marrow fibrosis, anemia, cytopenia, thrombocytosis, leukocytosis, and splenomegaly. While patients may respond to ruxolitinib, a selective inhibitor of Janus kinases 1 and 2, the drug does not always induce a long-term response.

An ongoing phase 2 study of parsaclisib, a selective inhibitor of the persistent phosphatidylinositol 3-kinase, suggests that, when combined with ruxolitinib, this treatment may help to induce a stable response among patients with myelofibrosis who show a suboptimal response to ruxolitinib only. The phase 2 trial suggested that the combination may help to mitigate disease symptoms and reduce splenomegaly.


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Because of these encouraging results, researchers are launching an international, phase 3 trial (LIMBER-304; ClinicalTrials.gov Identifier: NCT04551053) to determine the safety and efficacy of combination parsaclisib and ruxolitinib among patients previously treated with ruxolitinib only.

The study will be randomized, double-blinded, and placebo-controlled. Crossover will be possible after 24 weeks of treatment.

The study’s primary objectives will be to determine the proportion of patients who reach a predefined target in spleen size reduction by week 24, as compared with baseline. Spleen size will be determined by MRI or CT.

Secondary outcomes will include overall survival and incidence of adverse events. Patient-reported outcomes will also be evaluated.

The study is recruiting as of May 11, 2021.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Yacoub A, Stouffs M, Zhou F, Assad A. A randomized, double-blind, placebo-controlled phase 3 study of parsaclisib plus ruxolitinib in patients with myelofibrosis who have suboptimal response to ruxolitinib. Poster presented at: the British Society of Haematology 61st Annual Scientific Meeting; April 25-28, 2021; virtual.