| Exclusion Criteria: | 1) A subject with an active malignancy other than AML.
2) A subject who has known leptomeningeal leukemia requiring intrathecal therapy.
3) For Arm A and B, Part 1 only: a subject with a history of myelodysplastic syndrome (MDS). a. For Arm A and B, Part 2, subjects with AML in the background of MDS can be included (note this is after the 3+3 dose escalation and preliminary MTD determination).
4) A subject with isolated extramedullary leukemia without also meeting bone marrow criteria for acute leukemia.
5) A subject with AML blast crisis of Chronic Myelogenous Leukemia (CML).
6) A subject who has had a bond marrow transplant with active graft-versushost disease (GVHD) or who receives immunosuppressive therapy.
7) A subject with an uncontrolled active infection that requires systemic treatment,
8) A subject with clinically significant (CTCAE v. 4.0 based criteria) hepatitis at Screening, or a subject that is hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive (subjects with risk factors, or clinically suspected infection should be screened for Hepatitis B/C and/or HIV).
9) A subject with persistent, unresolved, drug-related toxicity CTCAE (common terminology criteria for adverse events) > Grade 2, that is associated with previous treatment, except for alopecia. The inclusion of subjects with persistent neuropathy or hearing loss >/= Grade 2 due to previous treatment requires discussion with the sponsor.
10) A subject who has any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.
11) A female subject who is breast-feeding, pregnant, intends to become pregnant or intends to breast feed during the study, or has a positive pregnancy test at Screening.
12) A subject participating in any other clinical study with a potentially therapeutic agent or who has received another investigational product within 5 half-lives (if the half-life is known) or 28 days (if the half-life is unknown) prior to Day 1 of Cycle 1. If there is a subject whose last dose was <28 days or 5 half-lives as above, but they have recovered from all toxicity, then discuss eligibility with sponsor.
13) A subject with any other medical or psychiatric condition which in the opinion of the investigator might interfere with participation in the trial or interfere with interpretation of the results.
14) A subject who, within the past 6 months, has had any of the following: myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack, or uncontrolled seizure disorder (i.e., seizures within the past 6 months).
15) A subject who, at the time of Screening, presents with: unstabel or uncontrolled angina, New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality.
16) A subject with a known bleeding disorder, e.g. hemophilia or disseminated intravascular coagulopathy or be on anti-coagulation therapy.
17) A subject unlikely to complete the study and appropriate follow-up visits.
18) The subject has received any treatment listed as Prohibited Medications During Screening and While on Treatment more recently than the indicated washout period prior to start of treatment or who must continue to receive treatment with the prohibited medications.
19) Subjects Screening for Arm B only: A subject with a known hypersensitivity to cytarabine. |