ABT-348 as Monotherapy and in Combination With Azacitidine to Treat Advanced Hematologic Malignancies

Inclusion Criteria: 1. Histological or cytological confirmation of one of the following (Arms A, B and D): * Relapsed or refractory acute myelogenous leukemia (AML), untreated AML in subjects who are \> 60 years of age and do not have favorable cytogenetics (i.e., lack t(8,21) or inv(16)/t(16,16) or acute lymphoblastic leukemia (ALL) in subjects who have failed or are unsuitable for standard therapy. * Chronic myelogenous leukemia (CML) subjects that have not responded or relapsed on imatinib and failed second line Tyrosine Kinase Inhibitor (TKI) therapy and are not a candidate for allogeneic bone marrow transplant. * B-cell chronic lymphocytic leukemia (CLL) subjects that have not responded or relapsed on fludarabine or in the opinion of the Principal Investigator are unsuitable for fludarabine therapy and have not responded to or relapsed on alkylating therapy. * Myelodysplasia (MDS) including chronic myelomonocytic leukemia (CMML) subjects with International Prognostic Scoring System (IPSS) risk categories of Intermediate-2 (INT-2) or High risk, or any myelodysplasia with symptomatic anemia resistant to erythropoietin, immunosuppressant, or DNA methyltransferase inhibitor therapy (e.g., azacitidine/decitabine). 1a. Histological or cytological confirmation of one of the following (Arm C): * Relapsed or refractory AML, untreated AML in subjects who are \> 60 years of age and do not have favorable cytogenetics (i.e., lack t(8,21). * Untreated MDS including CMML with IPSS risk categories of INT-2 or High risk or with more than 10% blasts in the bone marrow, or any myelodysplasia with symptomatic anemia resistant to erythropoietin, or immunosuppressant, or subject has no response after four cycles of DNA methyltransferase inhibitor therapy or subject has progressed on DNA methyltransferase inhibitor therapy. 2. Eastern Cooperative Oncology Group Status of 0-2 3. Hematologic function for subjects with CLL and CML demonstrated by hemoglobin \> 9 g/dL, platelets \> 100,000/µL, ANC \> 1500/mm3 4. Serum creatinine value of ≤ 1.8 times the upper limit of normal (ULN) and either an estimated creatinine clearance value as determined by the Cockcroft-Gault formula or based on a 24 hour urine collection creatinine clearance value of ≥ 50 mL/min 5. Adequate liver function as demonstrated by serum bilirubin \< 2 x ULN and AST and ALT \< 2.5 x ULN 6. QTc interval \< 500 msec 7. Left Ventricular Ejection Fraction \> 50% 8. Women of child-bearing potential and men must agree to use adequate contraception prior to the study entry, for the duration of study participation and up to 3 months following completion of therapy. 9. Capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures. Exclusion Criteria: 1. Subject has known active CNS involvement. The subject has untreated brain or meningeal metastases. 2. ALL or AML subject has received acute anti-cancer therapy within 14 days prior to Study Day 1 3. CML, CLL or myelodysplasia (MDS) subjects has received acute anti-cancer therapy within 28 days or biologic therapy within 6 weeks prior to Study Day 1. Per Investigator discretion, hydroxyurea may be used anytime during the study. Tyrosine kinase inhibitors may not be administered 7 days prior to Study Day 1. 4. Subjects with poorly controlled diabetes mellitus 5. Subject has unresolved toxicities from prior anti-cancer therapy, grade 2 or higher clinically significant toxicity (excluding alopecia) 6. Subject has had major surgery within 28 days prior to Study Day 1 7. Subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure \> 90 mmHg or systolic blood pressure \> 140 mmHg 8. Subject has proteinuria grade \> 1 9. Subject is unable to swallow or absorb oral tablets normally 10. Subject is receiving therapeutic anticoagulation therapy. Low-dose anticoagulation (e.g., low-dose heparin or warfarin) for catheter prophylaxis will be allowed 11. Subject has infection with HIV, Hepatitis B, or Hepatitis C 12. Female subjects who are pregnant or breast feeding 13. Any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities 14. Clinically significant uncontrolled condition(s) 15. Subjects in Arm C who have advanced malignant hepatic tumors 16. Subjects in Arm C who have hypersensitivity to azacitidine or mannitol 17. Subjects have received CYP3A inhibitors or inducers within 7 days prior to the first dose of study drug. 18. Subjects enrolled in Arm D who have hypersensitivity to drugs formulated with polyethoxylated castor oil (Cremophor).