Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms

Launched by UNIVERSITY OF WASHINGTON · Feb 21, 2020

Keywords

ClinConnect Summary

This clinical trial is exploring the effectiveness of a combination treatment using decitabine and other medications—ruxolitinib, fedratinib, or pacritinib—for patients with advanced myeloproliferative neoplasms (MPNs), which are a group of diseases that affect blood cell production. The goal is to see if this treatment can help prepare patients for a hematopoietic stem cell transplant, a procedure that can potentially cure these conditions by replacing unhealthy blood-forming cells with healthy ones from a donor.

To participate in the trial, individuals must be at least 18 years old and have a confirmed diagnosis of MPN with specific characteristics, such as having a certain percentage of abnormal cells (blasts) in their blood or bone marrow. Participants should be in good general health and able to provide informed consent. The trial is currently recruiting participants, and if you join, you can expect regular check-ups and monitoring to assess how well the treatment is working and to manage any side effects. If you're interested in taking part, it’s important to discuss this with your healthcare provider to see if you meet the eligibility criteria and if this trial is a good option for you.

Gender

ALL

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