Axitinib and Bosutinib for Patients With Chronic Myeloid Leukemia in Chronic, Accelerated or Blastic Phases

Inclusion Criteria:

1. Diagnosis of Ph+ (by cytogenetics or FISH) or BCR-ABL+ (by PCR) CML in CP (cohort 1),
AP (cohort 2) or BP (cohort 2).

2. Patients should have failed (demonstrated resistance, intolerance or treatment
discontinuation for any other reason of) at least 3 FDA-approved TKIs if in CP (cohort
1), or at least 1 FDA-approved TKI if in AP (cohort 2). Resistance will be defined as
meeting the criteria for failure or warning by the European LeukemiaNet (ELN,
Appendix)1. No prior therapy is necessary for patients in BP (cohort 2). Patients in
CP who have failed <3 TKIs, but are ineligible to receive other FDA-approved TKIs, may
also be enrolled in cohort 1. At least 10 CP patients with the T315I mutation
affecting the kinase domain of Bcr-Abl will be enrolled in cohort 1, as well as in the
phase II portion of cohort 2.

3. Age >/=18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

5. Adequate end organ function, defined as the following: total bilirubin (unless due to Gilbert syndrome, in which case it should be AST
6. Patients must sign the IRB-approved informed consent document for this trial.

7. Reliable telephone access so as to be able to receive calls from an IVR system (only
applicable to patients participating in the optional symptom burden assessment
portion).

8. Women of childbearing potential (WOCBP) must practice 2 effective methods of birth
control during the course of the study. Male patients who are partners of WOCBP should
also practice an effective method of contraception: Postmenopausal women must be
amenorrheic for >/= 12 months to be considered of non-childbearing potential. Women
and men must continue birth control for the duration of the trial and >/= 3 months
after the last dose of study drug. All WOCBP MUST have a negative pregnancy test prior
to first receiving study medication(s).

9. Patients should have discontinued therapy with imatinib, dasatinib, nilotinib,
ponatinib, omacetaxine or other anti-leukemia therapy (except hydroxyurea) >/= 48
hours prior to start of study therapy and recovered from any toxicity due to these
therapies to grade for the first 6 weeks of study treatment if necessary.

Exclusion Criteria:

1. Prior therapy with axitinib. Prior therapy with bosutinib is allowed, except in the
following circumstances: the subject is currently on bosutinib; bosutinib is the
subject's most recent TKI for CML; the subject has a history of intolerance to
bosutinib.

2. Active gastrointestinal conditions that are expected to impair absorption of orally
administered medications.

3. Patients who currently have or have a history of the following within 6 months
preceding study entry are not eligible: Unstable angina (UA), myocardial infarction
(MI), transient ischemic attack (TIA), stroke, deep vein thrombosis (DVT), acute
peripheral or pulmonary arterial thromboembolism (PE). Clinically significant
ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or
torsades de pointes). New York Heart Association class III or IV heart failure.

4. Patients with active, uncontrolled psychiatric disorders including: psychosis, major
depressive, and bipolar disorders.

5. Patients with uncontrolled hypertension (defined as sustained systolic blood pressure
> 160 mmHg or diastolic blood pressure >100 mmHg).

6. Pregnant or breast-feeding women are excluded.

7. Inability to understand a written informed consent document.

8. Patients receiving anticoagulants that are unable to be discontinued.

9. Patients with active, uncontrolled infection.

10. Patients with a history of hypersensitivity to bosutinib or axitinib.

11. Patients on proton pump inhibitors, potent CYP3A or P-glycoprotein substrates,
inhibitors or inducers a minimum 7 day period washout required unless discontinuation
or substitution is not in the best interests of the patient as determined by the
investigator. In instances where use of these agents is felt to be required for
optimal management, inclusion of such patients should be discussed with the PI and the
rationale documented. These patients, if enrolled on study, may require dose
modifications for both axitinib and bosutinib. The list of drugs that interact with
cytochrome P450 enzymes can be found online at:
http://medicine.iupui.edu/clinpharm/DDIs/ClinicalTable.aspx