Pacritinib plus azacitidine or decitabine to help people with accelerated or blast‑phase myeloproliferative neoplasms reach stem cell transplant.

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 trial tests if adding pacritinib to standard azacitidine or decitabine helps adults with accelerated or blast‑phase myeloproliferative neoplasms get to allogeneic stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Washington (Academic / other)
• Drugs / interventions: pacritinib, chemotherapy
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT07148947 on ClinicalTrials.gov

What this trial studies

This phase II trial gives oral pacritinib alongside standard hypomethylating therapy (azacitidine or decitabine/cedazuridine) for adults with accelerated or blast‑phase myeloproliferative neoplasms who are candidates for allogeneic transplant. Pacritinib is taken twice daily in 28‑day cycles while hypomethylating agents are given per local standard practice; pacritinib can begin 7 days before or up to 30 days after HMA initiation and treatment continues for up to six cycles. Patients have bone marrow and blood tests during treatment to monitor disease response and safety. After treatment, patients are followed for up to five years to document transplant rates and long‑term outcomes.

Who should consider this trial

Good fit: Adults (≥18) with a prior myeloproliferative neoplasm now in accelerated or blast phase (≥5% blasts) who are considered transplant candidates and meet performance status and organ function requirements.

Not a fit: Patients who are not transplant candidates, have severe organ dysfunction, or have uncontrolled infections are unlikely to benefit from this bridging approach.

Why it matters

Potential benefit: If successful, this approach could increase the number of patients who achieve disease control and proceed to potentially curative allogeneic stem cell transplantation.

How similar studies have performed: Combining hypomethylating agents with JAK‑pathway inhibitors has shown activity in related MPN/MDS settings, but using pacritinib specifically as a pre‑transplant bridge is relatively novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* Previous treatment with chemotherapy (e.g. hypomethylating agents or cytarabine-based regimens) for MPN (does not include the first cycle of treatment with an allowable HMA initiated within 30 days prior to start of pacritinib). Prior temporary measures to control blood counts is allowed. Prior treatment with hydroxyurea, interferons or JAK inhibitor therapy (including pacritinib) is allowed
* Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired \[e.g. chronic viral hepatitis, HIV\])
* Known hypersensitivity to any study drug
* Females who are pregnant or breastfeeding (Women of childbearing potential \[WOCBP\] must have a negative serum pregnancy test within 14 days prior to enrollment)
* Treatment with any other anti-MDS/leukemia investigational agent within 2 weeks of start of study drugs
* Corrected QT interval (QTC) \> 480 msec as measured by the Fridericia formula (changing of medications/supplementing electrolytes is allowed to determine if this helps QTc reduce to \< 480 msec)
* Concurrent use of a strong CYP3A4 inhibitor or inducer at enrollment that cannot be discontinued (washout period ≥ 5 half-lives prior to day 1)

Where this trial is running

Seattle, Washington

• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Anna Halpern, MD — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Anna Halpern, MD

Conditions Accelerated Phase Myeloproliferative Neoplasm; Blast Phase Myeloproliferative Neoplasm