Sorafenib Plus 5-Azacitidine Initial Therapy of Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MS) With FLT3-ITD Mutation

Inclusion Criteria: 1. Patients with untreated AML (\> or equal to 20% blasts in bone marrow and/or peripheral blood) or high risk MDS (\> or equal to 10% blasts in bone marrow). A. Patients with AML and history of MDS who have received prior therapy with a hypomethylating agent (including azacytidine) and/or with lenalidomide for prior MDS are eligible if the treating physician feels that participation in the study is in the patients' best interest. B. Patients should have molecular evidence of the presence of FLT3-ITD mutation with a molecular burden of at least 10%. 2. Age \> or equal to 60 years; patients younger than 60 who are unsuitable for or unwilling to receive standard cytotoxic chemotherapy are also eligible to be enrolled. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status \< or equal 2. 4. Adequate liver (bilirubin \< or equal to 1.5 x ULN, Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) \< or equal to 2.5 x ULN and Alkaline phosphatase \< or equal to 4 x ULN if not related to leukemic disease) and renal (creatinine \< or equal to 1.5 x ULN) function. 5. Patients must provide written informed consent. 6. Patients must have been off therapy for MDS for 2 weeks prior to entering this study, and must have recovered from the toxic effects of that therapy to at least grade 1, unless there is evidence of rapidly progressive disease. Use of hydroxyurea (any dose) or ara-C (up to 1 g/m\^2 X 2 doses) for patients with rapidly proliferative disease is allowed before the start of study therapy; these should be stopped for 24 hours prior to the initiation of azacitidine and sorafenib. 7. Women of childbearing potential should be advised to avoid becoming pregnant with an adequate method of contraception (barrier or hormonal methods) and men should be advised to not father a child while receiving treatment with azacitidine. All men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below: Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Men should use adequate birth control for at least 30 days after the last administration of sorafenib. Post-menopausal women (defined as no menses for at least one year) and surgically sterilized women are not required to undergo a pregnancy test. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. 8. 7\. Continued: Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study. 9. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures. 10. International Normalized Ratio (INR) \< or equal to 1.5. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored weekly, or as defined by the local standard of care, until INR is stable. Exclusion Criteria: 1. Nursing and pregnant females. 2. Patients with acute promyelocytic leukemia are excluded. 3. Patients with known allergy to sorafenib or azacitidine, mannitol or any of their components. 4. Patients with known severe impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of sorafenib. 5. Patients with any other known disease (except carcinoma in-situ) or concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and uncontrolled hypertension, chronic renal disease (creatinine clearance \< 20 ml/min using the Cockcroft and Gault formula), or active uncontrolled infection) which could compromise participation in the study. 6. Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis (B or C). 7. Patients who have had any major surgical procedure within 28 days prior to Day 1. 8. Patients unwilling or unable to comply with the protocol. 9. Cardiac disease: Congestive heart failure \> class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months. 10. Uncontrolled hypertension defined as systolic blood pressure \> 150? mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management. 11. Active clinically serious infection \> CTCAE v4, Grade 2 not controlled with antibiotics. 12. Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. 13. Pulmonary hemorrhage/bleeding event \> or equal to CTCAE v4. Grade 2 within 4 weeks of first dose of study drug. 14. Any other hemorrhage/bleeding event \> or equal to CTCAE v4. Grade 3 within 4 weeks of first dose of study drug. 15. Serious non-healing wound, ulcer, or bone fracture. 16. Evidence of bleeding diathesis or coagulopathy within the past 6 months. 17. Known or suspected allergy to sorafenib or any agent given in the course of this trial. 18. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results including known non-compliance issues on study trials. 19. Use of strong CYP3A4 inducer.