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

  • STATUS
    Recruiting
  • End date
    Nov 11, 2024
  • participants needed
    25
  • sponsor
    University of Washington
Updated on 26 February 2021
cancer
stem cell transplantation
myeloid leukemia
blast crisis
myelofibrosis
myelodysplastic syndromes
hydroxyurea
myeloproliferative disorder
cytarabine
white blood cell count
decitabine
ruxolitinib
leukemia
bone marrow procedure
gilbert's syndrome
blast cells
leukapheresis
hemolysis
white blood cells
thiamine
tumor cells
wbc count
leukostasis
blood cell counts
secondary myelofibrosis
polycythemia vera
myelodysplastic/myeloproliferative neoplasm
essential thrombocythemia
thrombocytosis
myeloproliferative/myelodysplastic disorders
fedratinib
mds/mpd
polycythemia
myelodysplastic/myeloproliferative neoplasms

Summary

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.

Description

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.

Details
Condition Bone marrow disorder, Preleukemia, Acute myeloid leukemia, Myelodysplastic-Myeloproliferative Diseases, Myelosclerosis with myeloid metaplasia, MYELOPROLIFERATIVE DISORDER, MYELODYSPLASTIC SYNDROME, ESSENTIAL THROMBOCYTHEMIA, Polycythemia Vera, Myelodysplastic Syndromes (MDS), Acute Myelogenous Leukemia (AML), Secondary Myelofibrosis, Myeloproliferative Neoplasms, Myelofibrosis, Myeloproliferative Neoplasm, Unclassifiable, Myeloproliferative Neoplasm, Unclassifiable, Myeloproliferative Neoplasm, Unclassifiable, Myeloproliferative Neoplasm, Unclassifiable, Myeloproliferative Neoplasm, Unclassifiable, myelodysplastic syndromes, myeloproliferative neoplasm, myeloproliferative disorders, myelodysplastic syndrome (mds), acute myelogenous leukemia, anll, acute myeloblastic leukemia, Myeloproliferative Neoplasm, Unclassifiable, Myeloproliferative Neoplasm, Unclassifiable, Myeloproliferative Neoplasm, Unclassifiable
Treatment questionnaire administration, Ruxolitinib, Decitabine, FEDRATINIB
Clinical Study IdentifierNCT04282187
SponsorUniversity of Washington
Last Modified on26 February 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Bone marrow disorder or Myelofibrosis or Secondary Myelofibrosis or Polycythemia Vera or MYELODYSPLASTIC SYNDROME or Preleukemia or Myelodysplastic Sy...?
Do you have any of these conditions: Polycythemia Vera or Bone marrow disorder or myelodysplastic syndromes or Myelodysplastic Syndromes (MDS) or Myeloproliferative Neoplasm, Unclassifiab...?
Do you have any of these conditions: Bone marrow disorder or Acute myeloid leukemia or Myelodysplastic Syndromes (MDS) or ESSENTIAL THROMBOCYTHEMIA or Polycythemia Vera or myeloproliferat...?
Do you have any of these conditions: Polycythemia Vera or Myeloproliferative Neoplasms or myelodysplastic syndrome (mds) or ESSENTIAL THROMBOCYTHEMIA or myelodysplastic syndromes or Secon...?
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
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