A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL228 Administered Intravenously to Subjects With Chronic Myeloid Leukemia (CML) or Philadelphia-Chromosome-Positive Acute Lymphocytic Leukemia (Ph+ ALL)
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
- 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
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.