Testing the Effect of Taking Ruxolitinib and CPX-351 in Combination for the Treatment of Advanced Phase Myeloproliferative Neoplasms

Inclusion Criteria

• •Ability to understand and the willingness to sign a written informed consent document
• •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• •Participants eligible for this study have either MPN in accelerated phase (AP) or blast phase (BP), defined as:
• •* MPN-AP is defined by 10% to 19% blasts in the peripheral blood or bone marrow
• •* MPN-BP is defined by \>= 20% blasts in the blood or bone marrow
• •* Either MPN-AP or MPN-BP requires a previous diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), primary or secondary myelofibrosis (MF), or MDS/MPN overlap with intermediate-2 or high risk disease according to IPSS as well as progression on or failure to respond to at least one line of therapy
• •* Participants with ET, PV, or MF that have received prior MPN-associated therapy (e.g., hydroxyurea, hypomethylating agents \[azacitidine, decitabine\], anti-platelet therapies \[e.g., aspirin, anagrelide\], as well as JAK2 inhibitor therapy \[e.g., ruxolitinib or other investigational JAK2 inhibitor\]) are eligible. They must discontinue prior to starting therapy; no wash-out is required
• •Female participants of childbearing potential must agree to use adequate contraception (2 forms of contraception or abstinence) from the screening visit until 30 days following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• •Male participants of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 90 days until the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment
• •Left ventricular ejection fraction at \>= 50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan (14 days prior to initiating study treatment)
• •Candidate for cytotoxic-intensive induction chemotherapy
• •Willing to take oral medication
• •Serum creatinine =\< 2 x the upper limit of normal (ULN), or glomerular filtration rate \> 20 ml/min/1.73m\^2 as calculated by Cockcroft-Gault formula
• •Serum potassium, magnesium, and calcium (corrected for albumin) within institutional normal limits or can be corrected with supplementation
• •Total serum bilirubin =\< 2.5 x ULN
• •Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =\< 2.5 x ULN