Inclusion Criteria:

• Diagnosis of CMML as defined by the World Health Organization (WHO) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Subject is willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures (including bone marrow assessments).
• At least 1 week since the last systemic therapy regimen prior to Cycle 1 Day 1. Subjects on a stable dose of hydroxyurea for at least 2 weeks prior to Cycle 1 Day 1 may continue on hydroxyurea until Cycle 1 Day 7. Subjects must have recovered to NCI CTCAE v. 4.03 < Grade 2 from all acute toxicities (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the Investigator.
• Acceptable liver function:
  1. Total or direct bilirubin ≤ 2 times upper limit of normal (x ULN); does not apply to subjects with Gilbert's syndrome diagnosed as per institutional guidelines.
  2. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN.
• Acceptable renal function with serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault or Modification of Diet in Renal Disease formulas.
• Female subjects must be:
  1. Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or
  2. If of child-bearing pIf of child-bearing potential, subject must use an adequate method of contraception consisting of two-barrier method or one barrier method with a spermicide or intrauterine device. Both females and male subjects with female partners of child-bearing potential must agree to use an adequate method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of study medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of study medication.
  3. Not breast feeding at any time during the study.
• Written and voluntary informed consent understood, signed and dated.

Exclusion Criteria:

• Known prior progression to acute myeloid leukemia (AML) defined by at least 20% blasts in the blood or bone marrow.
• Myeloproliferative/myelodysplastic syndrome other than CMML. CMML with t(5;12) that have not yet received imatinib.
• Participation in any interventional study within 4 weeks of randomization or 5 half-lives of the prior treatment agent (whichever is longer).
• Ongoing treatment with an anticancer agent for CMML not contemplated in this protocol. Subjects on a stable dose of hydroxyurea for at least 2 weeks prior to Cycle 1 Day 1 may continue on hydroxyurea until Cycle 1 Day 7.
• Concurrent use of granulocyte macrophage colony-stimulating factor (GM-CSF).
• Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.
• Active coronary artery disease requiring treatment, myocardial infarction within the prior year, New York Heart Association grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
• Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
• Active, concurrent malignancy requiring radiation, chemotherapy, or immunotherapy (excluding non-melanoma skin cancer, adjuvant hormonal therapy for breast cancer and hormonal treatment for castration sensitive prostate cancer).
• Active and uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with human immunodeficiency virus (HIV), or an active infection with hepatitis B or hepatitis C.
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
• The subject has legal incapacity or limited legal capacity.
• Significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.