Inclusion Criteria:
* Adults ≥ 18 years of age
* Diagnosis of one of the following:
* Accelerated-phase (≥ 10% blasts in PB or BM) or blast-phase (≥ 20% blasts in PB or BM) myeloproliferative neoplasm with a history of prior myelofibrosis, polycythemia vera, or essential thrombocythemia; or
* Chronic phase myelofibrosis with 4-9% circulating blasts
* Eastern Cooperative Oncology Group (ECOG) 0-2
* Concurrent use of physician's choice JAK1/2 inhibitors is permitted. Patients must be on stable dose of JAK2i for at least 4 weeks prior to starting the clinical trial.
* Body weight ≥ 41 kg
* Ability to swallow oral medication
* Adequate organ function as demonstrated by all of the following:
* ALT (SGPT) and/or AST (SGOT) \< 3x upper limit of normal (ULN), unless, upon judgment of the treating physician, it is believed to be due to MF-related extramedullary hematopoiesis (EMH)
* Direct bilirubin \< 2 x ULN; unless it is believed to be due to MF-related EMH or documented/suspected Gilbert's syndrome;
* Creatinine clearance ≥ 40 mL/min
* Women of childbearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months following completion of therapy. WCBP must also have a negative serum pregnancy test at screening and Cycle 1 Day 1. Should a woman become pregnant or suspect she is pregnant while participating, she should inform her treating physician immediately. Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 6 months after the last dose of study therapy
* Ability to adhere to the study visit schedule and all protocol requirements
* If the patient has co-morbid illness or malignancy, life expectancy attributed to this must be greater than 2 years.
Exclusion Criteria:
* Concurrent treatment with venetoclax
* Treatment with any MF-directed drug treatments (including investigational therapies; excluding hydroxyurea and JAK inhibitor) within 2 weeks or 5.5 half-lives, whichever is shorter, of Cycle 1 Day 1
* Prior treatment with more than 2 cycles of prior IV or subcutaneous (SC) hypomethylating agent
* Patients willing and able to undergo allogeneic stem cell transplant immediately without need for cytoreduction
* Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates, including, but not limited to:
* Ongoing or active infection
* Uncontrolled concurrent other malignancy
* Congestive heart failure of New York Heart Association (NYHA) class III/IV. Patients with compensated heart failure are permitted.
* Unstable angina pectoris
* New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted
* Decompensated liver cirrhosis (Child-Pugh score ≥12 or a MELD score ≥21)
* Psychiatric illness/social situations that would limit compliance with study requirements.
* Any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the patient or impair the assessment of study results.
* Hematopoietic cell transplant (HCT) within 100 days of the first dose of study therapy, receipt of immunosuppressive therapy post-HCT at screening, use of calcineurin inhibitors within 4 weeks prior to first dose of study therapy, or clinically significant GVHD
* Note: The use of topical steroids or \< 20mg oral prednisone for ongoing skin GVHD is permitted
* Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of oral THU-Dec, including any unresolved nausea, vomiting, or diarrhea \> NCI CTCAE grade 2
* Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject
* History of major surgery within 28 days prior to Cycle 1 Day 1 or any planned surgical procedures 10.
* Organ transplant recipients other than bone marrow transplant
* Women who are pregnant or lactating\\
* Concurrent enrollment in another interventional trial
