• Evaluate plasma pharmacokinetics and estimate renal elimination of once-weekly and twice-weekly 1-hour IV infusion of XL228 [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
• Exploratory Outcomes: Evaluate hematologic and cytogenetic response and pharmacodynamic correlates of XL228 activity [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]

• Evaluate plasma pharmacokinetics and estimate renal elimination of a single 1-hour IV infusion of XL228
• Exploratory Outcomes: Evaluate hematologic and cytogenetic response and pharmacodynamic correlates of XL228 activity in plasma after repeated weekly administration of XL228

The purpose of this study is to determine the safest dose of the BCR-ABL inhibitor XL228, how often it should be taken, and how well people with leukemia tolerate XL228.

• Chronic Myeloid Leukemia
• Leukemia, Lymphoblastic, Acute, Philadelphia-Positive

• Experimental: once-weekly dosing
• Experimental: twice-weekly dosing

Inclusion Criteria:

1. The subject has a confirmed pathologic diagnosis as evidenced by the presence of the BCR-Abl translocation [t(9;22)] by fluorescence in situ hybridization (FISH), cytogenetics, or quantitative polymerase chain reaction (QPCR) of one of the following:

   1. CML

      • Chronic phase (CP)
      • Accelerated phase (AP)
      • Blast phase (BP) OR
   2. Ph+ ALL

2. The subject has one of the following:

   • Known T315I Abl mutation
   • Known resistance to or intolerance of imatinib and dasatinib
   • At least one prior anti-leukemia therapy, including, but not limited to, interferon, imatinib, or dasatinib
3. The subject is at least 18 years old.
4. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
5. The subject has adequate organ function.
6. The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
7. Sexually active subjects must use an accepted method of contraception during the course of the study.
8. Female subjects of childbearing potential must have a negative pregnancy test at enrollment.

Exclusion Criteria:

1. The subject has received interferon, imatinib, or dasatinib within 7 days of the first dose of XL228.
2. The subject has received an investigational agent or radiotherapy within 28 days of the first dose of XL228.
3. The subject has received immunosuppressive therapy (eg, cyclosporine, steroids, tacrolimus for graft-versus-host disease [GVHD]) within 28 days prior to the first dose of XL228.
4. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤1 from toxicities related to peripheral stem cell or bone marrow transplant.
5. The subject has not recovered to CTCAE v3.0 Grade ≤1 from adverse events (AEs) due to investigational drugs or other medications.
6. The subject has known allergy or hypersensitivity to any component of the investigational drug product.
7. The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
8. The subject is pregnant or breastfeeding.
9. The subject is known to be positive for the human immunodeficiency virus (HIV).
10. The subject has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.