A Phase 2 Trial Investigating the Addition of Pacritinib to a Hypomethylating Agent as a Bridge to Allogeneic Hematopoietic Stem Cell Transplant in Patients With Accelerated and Blast Phase Myeloproliferative Neoplasms
This phase II trial tests if adding pacritinib to standard of care azacitidine or decitabine increases the number of patients able to proceed to hematopoietic stem cell transplantation (bridging) for patients with accelerated and blast phase myeloproliferative neoplasms. Pacritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Azacitidine and decitabine are in a class of medications called hypomethylation agents. They work by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Adding pacritinib to standard of care azacitidine or decitabine may increase the number of patients able to proceed to hematopoietic stem cell transplantation for patients with accelerated and blast phase myeloproliferative neoplasms.
• Age ≥ 18 years
• History of myeloproliferative neoplasms (MPN) as defined by the 2016 and 2022 World Health Organization criteria, with now pathologically confirmed ≥ 5% blasts in the bone marrow or peripheral blood. Prior MPNs could include polycythemia vera, essential thrombocythemia, primary myelofibrosis, secondary myelofibrosis, MPN-unclassifiable, and myelodysplastic syndrome (MDS)/MPN overlap syndromes
• Outside diagnostic material is acceptable. Internal review at the study institution of outside peripheral blood and/or bone marrow slides is recommended. Flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 OR Karnofsky ≥ 60%
• Serum creatinine clearance ≥ 50 ml/min calculated by the Cockcroft-Gault Equation (assessed within 14 days of study day 1)
• Total bilirubin ≤ 3 (total bilirubin \> 3 is allowable if thought due to Gilbert's disease, hemolysis, or MPN disease) (assessed within 14 days of study day 1)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 3 x upper limits of normal (ULN) (total bilirubin \> 3 is allowable if thought due to Gilbert's disease, hemolysis, or MPN disease) (assessed within 14 days of study day 1)
• Patient is considered a potential transplant candidate. The attending/treating physician will determine transplant candidacy at the time of consent
• Intention to initiate therapy with an HMA per treating physician's standard institutional practice. Allowable HMAs include:
‣ Azacitidine given IV or SC
⁃ Decitabine given IV, and
⁃ Decitabine given orally (as Inqovi \[cedazuridine/decitabine\]). If the HMA was already initiated, patients must be registered and start pacritinib within 30 days of initiation
• Hyperleukocytosis, white blood cell (WBC) \> 100,000/μL, or with concern for other complications of high tumor burden or leukostasis (e.g. hypoxia, disseminated intravascular coagulation) can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m\^2/dose) any time prior to enrollment
• Women of child-bearing potential and men must be agree to use a highly effective method of contraception, starting at the first dose of study therapy through 90 days after the last dose of study therapy
• Capable of providing valid informed consent