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

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Recruiting
participants needed

25
sponsor

University of Washington

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Updated on 19 February 2024

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cancer

white blood cell count

disseminated intravascular coagulation

thiamine

gilbert's syndrome

stem cell transplantation

myeloid leukemia

cytarabine

hydroxyurea

myelodysplastic syndromes

myeloproliferative disorder

decitabine

blast crisis

tumor cells

hyperleukocytosis

hypoxia

leukemia

leukapheresis

white blood cells

blood count

cancer care

bone marrow procedure

ruxolitinib

essential thrombocythemia

myelofibrosis

thrombocytosis

myeloproliferative/myelodysplastic disorders

hemolysis

leukostasis

polycythemia vera

blood cell count

polycythemia

secondary myelofibrosis

myelodysplastic/myeloproliferative neoplasms

fedratinib

myeloproliferative neoplasm

tumor burden

wbc count

blood cell counts

myelodysplastic/myeloproliferative neoplasm

mds/mpd

acute myeloid leukemia

myelodysplastic syndrome

chronic myeloproliferative disease

myelodysplastic/myeloproliferative disease

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 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	Preleukemia, Acute myeloid leukemia, Acute myeloid leukemia, Myelodysplastic-Myeloproliferative Diseases, Myelosclerosis with myeloid metaplasia, MYELOPROLIFERATIVE DISORDER, MYELODYSPLASTIC SYNDROME, ESSENTIAL THROMBOCYTHEMIA, Polycythemia Vera, Myeloproliferative Neoplasm, Unclassifiable, Secondary Myelofibrosis
Age	18years - 100years
Treatment	Decitabine, Ruxolitinib, Fedratinib
Clinical Study Identifier	NCT04282187
Sponsor	University of Washington
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
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 (assessed within 14 days of study day 1)
	Total bilirubin =< 3 unless due to Gilbert's disease or hemolysis (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 (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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cancer

white blood cell count

disseminated intravascular coagulation

thiamine

gilbert's syndrome

stem cell transplantation

myeloid leukemia

cytarabine

hydroxyurea

myelodysplastic syndromes

myeloproliferative disorder

bone marrow procedure

ruxolitinib

essential thrombocythemia

myelofibrosis

thrombocytosis

myeloproliferative/myelodysplastic disorders

secondary myelofibrosis

myelodysplastic/myeloproliferative neoplasms

fedratinib

myeloproliferative neoplasm

tumor burden

wbc count

blood cell counts

myelodysplastic/myeloproliferative neoplasm

mds/mpd

acute myeloid leukemia

myelodysplastic syndrome

chronic myeloproliferative disease

myelodysplastic/myeloproliferative disease

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Study Definition

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