Phase I Trial of Pacritinib in Combination With Venetoclax and Azacitidine for the Treatment of Accelerated and Blast Phase Myeloproliferative Neoplasms
Key claim: A phase I trial is evaluating the safety, tolerability, and optimal dosing of pacritinib combined with venetoclax and azacitidine in patients with accelerated and blast phase myeloproliferative neoplasms.
Abstract
This phase I trial studies the side effects and best dose of pacritinib when given together with venetoclax and azacitidine in treating patients with accelerated and blast phase myeloproliferative neoplasms (MPN-AP/BP). Pacritinib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving pacritinib together with venetoclax and azacitidine may be safe, tolerable, and/or effective in treating patients with MPN-AP/BP
Why this matters
AP/BP MPN patients have dismal outcomes without transplant, but current bridging strategies (chemotherapy or HMA ± single JAK inhibitor) often fail to achieve the disease control needed to reach alloHCT. Adding venetoclax to a pacritinib + azacitidine backbone tests whether concurrent BCL-2, JAK2, and hypomethylation pressure can improve pre-transplant response rates — potentially shifting more AP/BP MPN patients from ‘ineligible’ to ‘transplantable’ and altering the timing calculus for referral in this population.