Inclusion Criteria:

1. Histologically confirmed diagnosis of:

   • AML (including APL refractory to all-trans retinoic acid and arsenic) that has relapsed or was not responsive to prior chemotherapy;
   • Relapsed/refractory ALL;
   • CML that has failed to respond or has lost a response to imatinib; and
   • Advanced MDS (INT-2 and High risk by IPSS) with failure or intolerance to approved therapy.
2. ECOG Performance Status score of 0, 1, or 2;
3. Male or female, at least 18 years of age;
4. Signed written informed consent;
5. Serum creatinine ≤ 2.0 mg/dL;
6. Serum SGOT (AST) and SGPT (ALT) ≤ 5x ULN; serum bilirubin ≤ 2 mg/dL (serum bilirubin may be ≤ 3.0 mg/dL in any subject with Gilbert's Syndrome); and
7. For females of childbearing potential, a negative serum pregnancy test. Subjects, of childbearing potential, must use an Investigator-approved method of birth control.

Exclusion Criteria:

1. Candidates for approved therapies;
2. Concomitant treatment with any investigational agent, chemotherapy, radiotherapy, or immunotherapy;
3. Active CNS leukemia;
4. Previous or concurrent malignancy except noninvasive non-melanomatous skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 2 years prior to study entry;
5. Uncontrolled systemic infection (viral, bacterial, or fungal);
6. Uncontrollable disseminated intravascular coagulation;
7. Major surgery within the 28 days preceding the first dose KW-2449;
8. Radiotherapy, or lack of recovery of any radiotherapy-related acute toxicity, within the 28 days preceding the first dose KW-2449;
9. Treatment with systemic therapy for the underlying hematologic condition, or lack of recovery of toxicity from such treatment, within 28 days of the first dose of KW-2449, with the following exceptions: hydroxyurea for treatment of hyperleukocytosis (discontinued for at least 48 hours prior to the first dose of KW-2449); imatinib (discontinued for at least 48 hours prior to the first dose of KW-2449); and interferon (discontinued for at least 7 days prior to the first dose of KW-2449);
10. Treatment with any other investigational agent, or lack of recovery of toxicity from such treatment, within the 28 days preceding the first dose of KW-2449;
11. Positive serology for HIV;
12. Clinically significant cardiac dysfunction (New York Heart Association Class 3 or 4) at the time of screening, or a history of myocardial infarction or heart failure within 3 months preceding the first dose of KW-2449;
13. Any evidence of chronic Graft versus Host Disease;
14. Active autoimmune disease requiring immunosuppressive therapy;
15. Female subjects who are pregnant or breast feeding;
16. Subjects of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with the institution's standards;
17. Known current drug or alcohol abuse;
18. Other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may compromise the safety of the subject during the study, affect the subject's ability to complete the study, or interfere with interpretation of study results; or
19. For any reason is judged by the Investigator to be inappropriate for study participation, including an inability to communicate or cooperate with the Investigator.
20. Hematopoietic growth factors (i.e., such as erythropoietin or darbepoetin alpha, filgrastim [granulocyte colony-stimulating factor {G-CSF }], sargramostim [granulocyte-macrophage colony-stimulating factor {GM-CSF}], or other thrombopoietic agents) and corticosteroids within 14 days of study entry.