A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML)

Inclusion Criteria:

- Confirmed diagnosis of CMML using the World Health Organization (WHO) classification

- Age >18 years at the time of obtaining informed consent

- Must be able to adhere to the study visit schedule and other protocol requirements

- Must be able to provide adequate bone marrow (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

- Women of childbearing potential must have a negative pregnancy test at time of
screening and baseline visits and 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. The two methods of
reliable contraception must include one highly effective method (i.e. intrauterine
device [IUD], hormonal [birth control pills, injections, or implants], tubal
ligation, partner's vasectomy) and one additional effective (barrier) method (i.e.
latex condom, diaphragm, cervical cap).

- Must understand and voluntarily sign an informed consent form

- Must have a life expectancy of greater than 3 months at time of screening

Exclusion Criteria:

- Platelet count of less than 35,000/uL

- Absolute Neutrophil Count (ANC) of less than 250 cells/uL

- Serum creatinine > 2 upper limit of normal (ULN)

- Serum aspartic transaminase(AST) or alanine transaminase(ALT) >2.5 x ULN

- Serum total bilirubin >2.5 x 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

- 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

- History of metastatic malignancy in the preceding 2 years

- Pregnant women are excluded from this study because ruxolitinib has not been studied
in pregnant subjects. 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.

- Patients who have participated in other interventional (treatment-related) clinical
trials within 30 days of enrollment are excluded.