Combining decitabine with ruxolitinib, fedratinib, or pacritinib for treating advanced myeloproliferative neoplasms

A Phase 2 Trial Investigating Decitabine in Combination With a JAK-Inhibitor as a Bridge to Allogeneic Hematopoietic Stem Cell Transplant in Patients With Accelerated/Blast Phase Myeloproliferative Neoplasms

This study is testing if combining decitabine with other medications can help patients with advanced blood cancers get ready for a stem cell transplant.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Washington (other)
• Drugs / interventions: fedratinib, ruxolitinib, pacritinib, chemotherapy
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT04282187 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of decitabine in combination with ruxolitinib, fedratinib, or pacritinib for patients with accelerated or blast phase myeloproliferative neoplasms prior to hematopoietic stem cell transplant. The study aims to evaluate how these drugs work together to inhibit tumor cell growth and prepare the patient's bone marrow for transplant. Participants will receive treatment for up to six cycles, followed by a follow-up period of up to five years to assess long-term outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of myeloproliferative neoplasm exhibiting at least 5% blasts in their bone marrow or peripheral blood.

Not a fit: Patients with less than 5% blasts or those with other unrelated health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with advanced myeloproliferative neoplasms.

How similar studies have performed: While this approach is novel, similar studies combining chemotherapy with targeted therapies have shown promise in treating hematological malignancies.

Eligibility criteria

Inclusion Criteria:

* Age \>= 18 years
* History of MPN as defined by the 2016 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, MDS/MPN overlap
* 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 unless due to Gilbert's disease or hemolysis (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 limit of normal (ULN) unless thought to be due to MPN disease process (AST/ALT \> 3 is allowable if thought due to MPN disease) (assessed within 14 days of study day 1)
* For patient receiving fedratinib, thiamine level should be above the laboratory lower limit of normal (\>= 70 nmol/L in the University of Washington \[UW\]/Seattle Cancer Care Alliance \[SCCA\] lab). If it is low, it may be repleted but should be rechecked and demonstrated to normalize prior to initiation of therapy
* Patient is considered a potential transplant candidate. The attending/treating physician will determine transplant candidacy at the time of consent
* The use of hydroxyurea prior to study registration is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood count (WBC) \> 100,000/uL, 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) anytime prior to enrollment
* Capable of providing valid informed consent

Exclusion Criteria:

* Previous treatment with chemotherapy (e.g. hypomethylating agents or cytarabine-based regimens) for MPN with \>= 5% blasts in the blood or marrow. Prior temporary measures to control blood counts is allowed. Prior treatment with hydroxyurea, interferons or JAK inhibitor therapy 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 \[e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)\])
* Known hypersensitivity to any study drug
* Females who are pregnant or breastfeeding
* Treatment with any other anti-MDS/leukemia investigational agent within 2 weeks of start of study drugs
* For patients planning to receive fedratinib: concurrent use of strong and moderate CYP3A4 inducers or dual CYP3A4 and CYP2C19 inhibitors that cannot be discontinued
* For patients planned to receive ruxolitinib AND platelets \< 50,000/mm\^2: concurrent use of a strong CYP3A4 inhibitor that cannot be discontinued
* For patients planned to receive pacritinib, corrected QT interval (QTc) \> 480 msec (changing of medications/supplementing electrolytes is allowed to determine if this helps QTc reduce to \< 480 msec)
* For patients planned to receive pacritinib, concurrent use of medications that are CYP1A2, CYP3A4, P-gp, BCRP, OCT1 substrates that cannot be discontinued

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 — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Noah Pinke

Conditions: Acute Myeloid Leukemia, Essential Thrombocythemia, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm, Myeloproliferative Neoplasm, Myeloproliferative Neoplasm, Not Otherwise Specified, Polycythemia Vera, Primary Myelofibrosis