This phase II trial studies how well decitabine with ruxolitinib, fedratinib, or pacritinib 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, fedratinib, and pacritinib 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, fedratinib, or pacritinib may work better than multi-agent chemotherapy or no pre-transplant therapy, in treating patients with accelerated/blast phase myeloproliferative neoplasms.
OUTLINE: Patients receive decitabine intravenously (IV) once daily (QD) over 1 hour on days 1-10, and either ruxolitinib orally (PO) twice daily (BID), fedratinib PO daily, or pacritinib PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and bone marrow samples throughout the trial. After completion of study treatment, patients are followed up for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Given IV
Given PO
Given PO
Ancillary studies
Given PO
Undergo collection of blood and bone marrow samples
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGProportion of patients enrolled who receive hematopoietic stem cell transplantation (HCT)
Time frame: Up to 5 years
Time from diagnosis of myeloproliferative neoplasm (MPN)-accelerated phase (AP)/blast phase (BP) to day 0 of HCT
Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Time frame: Up to day 0 of HCT
Remission rate
Assessed via the Mascarenhas criteria. Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Time frame: At day 100
Overall survival
Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Time frame: From day 0 of HCT, assessed until 12 months post HCT
Relapse-free survival
Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Time frame: From day 0 of HCT, assessed until 12 months post HCT
Mutational profiling
Mutational data will be descriptive. The study team will record mutations found on the next generation of sequencing assays and will watch how these profiles change over time
Time frame: Up to 5 years
Response rates regardless of transplant status
Assessed via Mascarenhas criteria. Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Time frame: From day 1 of study treatment, assessed up to 5 years
Overall survival regardless of transplant status
Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Time frame: From day 1 of study treatment, assessed up to 5 years
Relapse-free survival regardless of transplant status
Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Time frame: From day 1 of study treatment, assessed up to 5 years
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