Pacritinib With Standard of Care Azacitidine or Decitabine as a Bridge to Allogeneic Hematopoietic Stem Cell Transplant for Patients With Accelerated and Blast Phase Myeloproliferative Neoplasms

University of Washington

Status and phase

Not yet enrolling

Phase 2

Conditions

Accelerated Phase Myeloproliferative Neoplasm

Blast Phase Myeloproliferative Neoplasm

Treatments

Drug: Decitabine

Procedure: Bone Marrow Biopsy

Procedure: Bone Marrow Aspiration

Procedure: Biospecimen Collection

Drug: Pacritinib

Other: Survey Administration

Drug: Azacitidine

Drug: Decitabine and Cedazuridine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT07148947

NCI-2025-05720 (Registry Identifier)

RG1125470

Details and patient eligibility

About

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.

Full description

OUTLINE:

Patients receive pacritinib orally (PO) twice daily (BID) on days 1-28 of each cycle, starting 7 days before or 30 days after standard of care hypomethylating agent (HMA) bridge therapy. Cycles repeat every 28 days for 6 cycles. Patients receive HMA bridge therapy per treating physician's standard institutional practice with azacitidine intravenously (IV) or subcutaneously (SC), or decitabine IV or cedazuridine/decitabine PO per standard of care. Treatment is given in the absence of unacceptable toxicity. Patents also undergo bone marrow aspiration and/or biopsy and blood sample collection during screening and as clinically indicated throughout the study.

After completion of study treatment, patients are followed up periodically for up to 5 years.

Enrollment

27 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 as long as peripheral blood and/or bone marrow slides are reviewed at the study institution by pathology. 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)

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

27 participants in 1 patient group

Treatment (pacritinib and HMA bridge therapy)

Experimental group

Description:

Patients receive pacritinib PO BID on days 1-28 of each cycle, starting 7 days before or 30 days after standard of care HMA bridge therapy. Cycles repeat every 28 days for 6 cycles. Patients receive HMA bridge therapy per treating physician's standard institutional practice with azacitidine IV or SC, or decitabine IV or cedazuridine/decitabine PO per standard of care. Treatment is given in the absence of unacceptable toxicity. Patents also undergo bone marrow aspiration and/or biopsy and blood sample collection during screening and as clinically indicated throughout the study.

Treatment: