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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
OHSU
Portland, Oregon, United States
Simmons Cancer Center
Dallas, Texas, United States
Dose limiting toxicity (DLT) (Phase I)
DLT occurrence after exposure to ruxolitinib and CPX-351.
Time frame: Day 1 to day 42
Proportion of participants that achieve at least an Acute Leukemia Response-Partial response (>= ALR-P, per 2012 myeloproliferative neoplasm - blast phase [MPN-BP] criteria) (Phase 2)
Will compute the proportion of efficacy-evaluable participants achieving overall response rate (ORR) and the exact binominal 95% confidence interval.
Time frame: Day 1 to end of induction or re-induction cycle (or upon assessment of the bone marrow biopsy performed near the end of these cycles if this occurs later). Cycle length is 28 days.
Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
The incidence of treatment-related toxicity and the exact confidence interval will be measured. Each toxicity event will be tabulated and summarized by severity and major organ site according to the CTCAE version (v)5.0.
Time frame: Day 1 to end of 6 cycles with study intervention
Incidence of adverse events as assessed by CTCAE version 5.0
The incidence of treatment-related toxicity and the exact confidence interval will be measured. Each toxicity event will be tabulated and summarized by severity and major organ site according to the CTCAE v5.0.
Time frame: Up to 30 days after last on-study dose
Overall survival (OS)
Time-to-event analysis (e.g., Kaplan-Meier curves or cumulative incidence curves) will be used to evaluate overall survival.
Time frame: 1 year post treatment
Event-free survival (EFS)
Time-to-event analysis (e.g., Kaplan-Meier curves or cumulative incidence curves) will be used to evaluate event-free survival.
Time frame: Day 1 to treatment failure, progressive disease, relapse, last exam date, or death (whichever is first), up to 2 years
Relapse-free survival (RFS)
Time-to-event analysis (e.g., Kaplan-Meier curves or cumulative incidence curves) will be used to evaluate relapse-free survival.
Time frame: Date of first documented response (ALR-C) to date of relapse or death from any cause, up to 2 years.
Remission duration
Time-to-event analysis (e.g., Kaplan-Meier curves or cumulative incidence curves) will be used to evaluate remission duration.
Time frame: Date of first documented response (ALR-C) to date of documented relapse, up to 2 years
Proportion of participants proceeding to transplant
A point estimate and 95% confidence interval will be computed for the proportion of participants who undergo an allogeneic (allo)-SCT (stem cell transplant).
Time frame: Date of enrollment to time of transplant or end of follow-up (if no transplant), up to 2 years
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