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

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.