This study is to find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug (ruxolitinib) can improve outcomes of patients with CMML.

Inclusion Criteria:

• Confirmed diagnosis of Chronic Myelomonocytic Leukemia (CMML)using the World Health Organization (WHO) classification.
• 18 years of age or older at the time of obtaining informed consent.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Participants must be able to provide adequate BM aspirate and biopsy specimens for histopathological analysis and standard cytogenetic analysis during the screening procedure.
• An Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 is required.
• Women of childbearing potential must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.
• Must understand and voluntarily sign an informed consent form.
• Must have a life expectancy of greater than 3 months at time of screening.
• Must have symptomatic splenomegaly and/or an Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score >17.

Exclusion Criteria:

• Any of the following lab abnormalities: Platelet count of less than 35,000/uL, Absolute Neutrophil Count (ANC) less than 250/uL, Serum Creatinine ≥ 2.0, Serum total bilirubin >1.5x ULN
• Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of CMML within 28 days of the first day of study drug treatment.
• Prior history of metastatic malignancy in past 2 years
• Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.
• Concurrent use of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). Granulocyte Colony Stimulating Factor (G-CSF) could be used for the short-term management of neutropenic infection. Stable doses of erythropoietin stimulating agents that were started >8 weeks from first ruxolitinib dose or corticosteroids that were being administered prior to screening are allowed.
• Uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because ruxolitinib has not been studied in pregnant participants. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib.