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

This phase I/II trial studies the best dose of ruxolitinib when given together with CPX-351 and to see how well they work in treating patients with accelerated phase or blast phase myeloproliferative neoplasm. Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. CPX-351 is a mixture of 2 chemotherapy drugs (daunorubicin and cytarabine) given for leukemia in small fat-based particles (liposomes) to improve the drug getting into cancer cells. Giving ruxolitinib and CPX-351 may work better in treating patients with secondary acute myeloid leukemia compared to CPX-351 alone.

PRIMARY OBJECTIVES: I. To identify the maximum-tolerated dose (MTD) of ruxolitinib in combination with liposome-encapsulated daunorubicin-cytarabine (CPX-351). (Phase I) II. To evaluate the objective response rate in participants with post-myeloproliferative neoplasm (MPN)- accelerated phase (AP)/blast phase (BP) following treatment with the combination of ruxolitinib and CPX-351 (per 2012 MPN-BP criteria). (Phase II) SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of ruxolitinib in combination with CPX-351. (Phase I) II. Assess survival outcomes and proportion of patients receiving transplant associated with ruxolitinib in combination with CPX-351. (Phase II) EXPLORATORY OBJECTIVES: I. To evaluate the rate of response among participants with MPN-AP/BP using European Leukemia Net (ELN) criteria. II. Assess the proportion of treated participants with minimal residual disease. (Phase II) OUTLINE: This is a phase I, dose-escalation study of ruxolitinib followed by a phase II study. INDUCTION: Patients receive CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5 and ruxolitinib orally (PO) twice daily (BID) on days 6-28 of cycle 1. RE-INDUCTION: Patients with significant residual disease may receive CPX-351 IV on days 1 and 3 and ruxolitinib PO BID on days 4-28 of cycle 2 per the discretion of the treating physician. Patients who have persistent disease following 2 cycles of therapy (induction and re-induction) will be offered salvage chemotherapy. CONSOLIDATION: Patients that have =\< 5% blasts in bone marrow receive CPX-351 IV on days 1 and 3 and ruxolitinib PO BID on days 4-28. Treatment repeats every 28 days for up to 2 cycles provided that counts have partially recovered in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients who successfully complete consolidation therapy with a continued =\< 5% blasts in bone marrow and have not undergone an allogeneic stem cell transplantation (SCT) receive ruxolitinib PO BID on days 1-28. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. ALLOGENEIC STEM CELL TRANSPLANTATION: Patients may undergo an allogeneic SCT at any time after achieving =\< 5% blasts in bone marrow if they have a suitable donor. After completion of study treatment, patients are followed up at 30 days and then every 2 months for up to 1 year.