Ruxolitinib in Treating Participants With Chronic Myeloid Leukemia With Minimal Residual Disease While on Therapy With Tyrosine Kinase Inhibitors

PRIMARY OBJECTIVES: I. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination of ruxolitinib and a tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML). (Phase I) II. To determine the clinical activity of the combination of ruxolitinib and a TKI in patients with CML in complete cytogenetic remission (CCyR) with minimal residual disease (MRD). (Phase II) SECONDARY OBJECTIVES: I. To determine the clinical activity of the combination of ruxolitinib and a TKI in patients with CML. (Phase I) II. To determine the safety of the combination of ruxolitinib and a TKI in patients with CML in CCyR with minimal residual disease. (Phase II) III. Determine the overall survival, event-free survival and survival free from transformation to accelerated and blast phase. (Phase I and II) IV. Determine the effect of therapy on bone marrow progenitors in clonogenic assays. (Phase I and II) V. Investigate the effect of therapy on molecular responses as assessed by genomic deoxyribonucleic acid (DNA) polymerase chain reaction (PCR). (Phase I and II) VI. Determine the effect of therapy on TKI-resistant quiescent leukemic Philadelphia chromosome (Ph)+ stem cells (CFSEmax/CD34+) by flow cytometric evaluation of activated Crkl and Jak2. (Phase I and II) VII. Assess the effect of therapy on self-renewal and/or survival of leukemic stem cells by fluorescence in situ hybridization (FISH) analysis on colonies. (Phase I and II) VIII. Assess ruxolitinib pharmacokinetics (PK) in preselected time intervals during co-administration of this agent with TKIs. (Phase I and II) OUTLINE: This is a phase I, dose-escalation study of ruxolitinib followed by a phase II study. Participants receive commercially available TKIs (imatinib mesylate, nilotinib, or dasatinib) as they had been receiving during the last 6 months and ruxolitinib orally (PO) twice daily (BID). Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up for 30 days.