|Inclusion Criteria:||1) Patients with AML or RAEB-2 High-Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated. Eligible patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS may have had one approved prior targeted therapy (eg, azacytadine or decitabine) for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML.|
2) AML patients include de-novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML). For a diagnosis of AML, a bone marrow blast count of 20% or more is required; For AML defined by cytogenetic aberrations t(8;21), inv(16) or t(16;16) and some cases of erythroleukemia the proportion of bone marrow blasts may be <20%; In AML FAB M6a (erythroid leukemia) >/=30% of non-erythroid cells in the bone marrow must be leukemic blasts; In AML with monocytic or myelomonocytic differentiation, monoblasts and promonocytes, but not abnormal monocytes, are counted as blast equivalents.
3) For a diagnosis of high-risk Myelodysplastic Syndrome RAEB-2 the patient must have 10-19% bone marrow blasts.
4) Men and women >/= 18 years old.
5) ECOG Performance Status 0, 1, or 2.
6) Patients with AML or High-Risk MDS who are age 18 years or older and have one or more of the criteria below are considered "unfit" for intensive chemotherapy and are eligible for Arms A and B only: Age >/= 75 years; ECOG of 2; Serum creatinine >1.3 mg/dL; Severe cardiac disease (eg, LVEF < 45% by multigated acquisition [MUGA] or echocardiography [ECHO] at screening).
7) Patients with AML or high risk MDS who are age 18 to 74 years and have none of the following criteria are considered "fit" for more intensive chemotherapy and are eligible for Arm C only: ECOG of 2; Serum creatinine >1.3 mg/dL; Severe cardiac disease (eg, LVEF < 45% by MUGA or ECHO at screening).
8) Adequate Organ Function as defined by the following: Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) </=3 x upper limit of normal (ULN), or AST and ALT </=5 x ULN if liver function abnormalities are due to underlying malignancy; Total serum bilirubin </=2 x ULN (except patients with documented Gilbert's syndrome); Serum creatinine </=1.5 x ULN or estimated creatinine clearance >/=60 mL/min as calculated using the method standard for the institution.
9) All anti-cancer treatments (unless specified) should be discontinued >/=2 weeks from study entry, for example: targeted chemotherapy, radiotherapy, investigational agents, hormones, anagrelide or cytokines; For control of rapidly progressing leukemia, hydroxyurea or leukapheresis may be used before and for up to 1 week after first dose of PF-04449913 for all three arms of the study; Patients with controlled CNS leukemia (documented by two consecutive assessments of zero blast count in cerebrospinal fluid), and who are still receiving intrathecal (IT) therapy at study entry are considered eligible, and will continue to receive IT therapy.
10) Resolved acute effects of any prior therapy to baseline severity or Grade </=1 CTC AE except for AEs not constituting a safety risk by investigator judgment.
11) Serum/urine pregnancy test (for females of childbearing potential) that is negative within 72 hours prior to initiation of treatment (first dose). Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 90 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
12) Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study.