Inclusion Criteria:

• Patients must have a diagnosis of primary or therapy-related myelodysplastic syndrome or myelodysplastic/ myeloproliferative disorders as defined by the WHO

  • Refractory anemia with excess blasts - 1 or 2
  • Chronic myelomonocytic leukemia type 2
  • Refractory anemia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, refractory cytopenia with multilineage dysplasia with ringed sideroblasts, 5q- syndrome, myelodysplastic syndrome unclassified or chronic myelomonocytic leukemia type 1 if at least one of the following criteria is met: HgB < 10 g/dl, Platelets < 50,000/ul,ANC < 1,000 ul, Transfusion dependent defined as 2 transfusions within an 8 week period.
• Patients may have low, intermediate-1, intermediate-2 or high risk MDS or CMML.
• Patients are eligible without regard to prior treatment status except for allogenic bone marrow transplant.
• Patients must be 18 years of age or older.
• Patient has an estimated or measured creatinine clearance ≥30 ml/min at study enrollment.
• AST, ALT, total bilirubin ≤ than 2.5 times the upper limit of normal.
• ECOG performance status of 0-2.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control.
• Male subject agrees to use an acceptable method for contraception for the duration of the study therapy and for 2 weeks after study completion.

Exclusion Criteria:

• Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result within 2 weeks of enrollment. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs for this disease within 14 days of enrollment
• No growth factor support with erythropoietin, GCSF, or GMCSF within 28 days of enrolling in the study.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patients with another malignancy within the last one year (from documentation of remission) other than basal or squamous cell skin cancer or CIS of the cervix.
• Patients who underwent allogeneic stem cell transplant will be excluded.
• History of leukemia (having more than 20% blasts in blood or marrow)
• Current treatment with coumadin, heparin and its derivatives.
• Major surgery (including needle biopsy of visceral organs) for 1-month prior to study and fully recovered. In addition, no placement of a subcutaneous or tunneled venous access device for 3 days prior to study and adequately healed.
• Significant cardiac or vascular events within 6 months: acute MI, unstable angina, severe peripheral vascular disease (ischemic pain at rest class 3 or worse, non-healing ulcers/wounds, congestive heart failure (NHYA class ≥ 2), uncontrolled cardiac arrhythmias, and disseminated intravascular coagulation.
• No use of hematopoetic growth factors within 4 weeks of starting sorafenib.
• Known severe hypersensitivity to Sorafenib or any component of the formulation.
• Caution should be exercised with the concomitant use of other CYP3A4 inducers, such as rifampin, St. John's Wort, phenytoin, phenobarbital and dexamethasone.
• Uncontrolled hypertension with a systolic blood pressure greater than 160 or a diastolic blood pressure greater than 100 despite treatment.