Skip to main content

Decitabine with Ruxolitinib or Fedratinib for the Treatment of Accelerated / Blast Phase Myeloproliferative Neoplasms

Trial Status: Active

This phase II trial studies how well decitabine with ruxolitinib or fedratinib works before hematopoietic stem cell transplant in treating patients with accelerated / blast phase myeloproliferative neoplasms (tumors). Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ruxolitinib and fedratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy before a donor hematopoietic stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient’s immune cells and help destroy any remaining cancer cells. Decitabine, with ruxolitinib or fedratinib, may work better than multi-agent chemotherapy or no pre-transplant therapy, in treating patients with accelerated / blast phase myeloproliferative neoplasms.

Inclusion Criteria

  • Pathologically confirmed diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with >= 5% myeloblasts in either bone marrow or peripheral blood felt to be transformed out of an MPN as defined by the 2016 World Health Organization criteria, consisting of polycythemia vera, essential thrombocythemia, primary myelofibrosis, secondary myelofibrosis, MPN-unclassifiable, or 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 progressed to MDS or AML. 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

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE
Contact: Anna Halpern
Phone: 206-606-1978

PRIMARY OBJECTIVE:

I. To determine whether patients with myeloproliferative neoplasm (MPN)-accelerated phase (AP)/blast phase (BP) being treated with decitabine and a JAK-inhibitor are more likely to proceed to hematopoietic stem cell transplant (HCT) than historical control patients treated with multi-agent chemotherapy or not receiving pre-transplant therapy.

SECONDARY OBJECTIVES:

I. To assess the time from diagnosis of MPN-AP/BP to HCT, compared to historical control patients treated with multi-agent chemotherapy or no pre-transplant therapy.

II. To assess whether patients with MPN-AP/BP who are treated with decitabine and a JAK-inhibitor are more likely to be in remission at day 100 post HCT than historical control patients treated with multi-agent chemotherapy or not given pre-transplant therapy.

III. To determine whether patients with MPN-AP/BP who are treated with decitabine and a JAK-inhibitor are more likely to be alive at 12 months post HCT than historical control patients treated with multi-agent chemotherapy or not given pre-transplant therapy.

IV. To assess the longitudinal mutational landscape in these patients at different stages of disease.

V. To describe response rates to this regimen and overall and relapse-free survival following this regimen, regardless of subsequent transplant status.

OUTLINE:

Patients receive decitabine intravenously (IV) once daily (QD) over 1 hour on days 1-10, and either ruxolitinib orally (PO) twice daily (BID) or fedratinib PO daily on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

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

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Fred Hutch / University of Washington Cancer Consortium

Principal Investigator
Anna Halpern

  • Primary ID RG1006644
  • Secondary IDs NCI-2020-00749
  • Clinicaltrials.gov ID NCT04282187