Phase I/II Study of Bosutinib in Combination With Inotuzumab Ozogamicin in CD22-positive Philadelphia-Chromosome (PC) Positive Acute Lymphoblastic Leukemia (ALL) and Chronic Myeloid Leukemia (CML)

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study and whether or not you have received earlier
treatment for leukemia. Up to 36 participants will be enrolled in Part 1 of the study, and up
to 44 participants will be enrolled in Part 2.

If you are enrolled in Part 1, the dose of bosutinib you receive will depend on when you join
this study and your treatment history. The first group of participants in each treatment
history group will receive the lowest dose level of bosutinib. Each new group will receive a
higher dose of bosutinib than the group before it, if no intolerable side effects were seen.
This will continue until the highest tolerable dose of bosutinib is found.

If you are enrolled in Part 2, you will receive bosutinib at the highest dose that was
tolerated in Part 1.

All participants in Parts 1 and 2 will receive the same dose of inotuzumab ozogamicin.

Study Drug Administration:

You will take bosutinib tablets by mouth 1 time each day with food. If you miss or vomit a
dose of bosutinib, do not take "make up" the dose. Wait and take your next dose as scheduled
the next day.

You will also receive inotuzumab ozogamicin by vein over about 1 hour on Days 1, 8, and 15 of
each 28-day cycle. If the doctor thinks it is needed, you may switch to a different dosing
schedule and receive inotuzumab ozogamicin 1 time every 4 weeks. The doctor will discuss this
with you.

You will be given standard drugs (such as acetaminophen/paracetamol, antihistamines, and/or
steroids) to help decrease the risk of side effects. If your doctor thinks it is needed, you
may also receive hydroxyurea to control your white blood cell count while you are on study.
You may ask the study staff for information about how these drugs are given and their risks.

Study Visits:

On Day 1 of all cycles and Days 8 and 15 of Cycle 1:

- Blood (about 3 teaspoons) will be drawn for routine tests.

- You will have a physical exam. On Day 8 of Cycle 1, you will not have this exam.

You may have these routine blood draws performed at a local lab or clinic closer to your
home. The results will be sent to the study doctor for review.

On Day 1 of Cycles 2-6, you will have a bone marrow aspirate/biopsy to check the status of
the disease and for CD22 testing. If the disease appears to get better, you will have this
test every 2 cycles. After Cycle 6, you will have this test every 3 months or at any time the
doctor thinks it is needed.

Length of Treatment:

You may take the inotuzumab ozogamicin for up to 6 cycles. You may continue taking bosutinib
for as long as the doctor thinks it is in your best interest. You will no longer be able to
take the study drugs if the disease gets worse, if intolerable side effects occur, or if you
are unable to follow study directions.

Your participation on the study will be over after 1 year of follow-up calls.

End-of-Treatment Visit:

About 28 days after your last dose of study drugs:

- You will have a physical exam.

- Blood (about 4 teaspoons) will be drawn for routine tests and for CD22 testing.

- If the doctor thinks it is needed, you will have a bone marrow aspirate/biopsy to check
the status of the disease and for CD22 testing.

If you cannot come to MD Anderson for the clinic visit, you will be called by a member of the
study staff and asked about any side effects you may have. This call will last about 5
minutes.

Follow-Up:

After your end-of-treatment visit or call, you will be called 1 time about every 12 weeks
(for up to 1 year) and asked about any anti-cancer therapy you may have started. This call
will last about 5 minutes.

Inclusion Criteria:

1. Relapsed or refractory B-cell ALL or CML in lymphoid blast phase. Philadelphia
chromosome must be present at screening (as determined by cytogenetic analysis, FISH,
or PCR [i.e., BCR-ABL positive]). Note: patients with CML who have received treatment
with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast
phase are eligible for frontline treatment. Frontline Ph+ ALL or CML-LBC Cohort:
Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal
treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of 2 week duration; vincristine duration; /=60 years or older are eligible.
Patients must have bone marrow blasts >5% at the time of screening.

2. Expression of CD-22 in > or = 20% blasts

3. Age 18 years or older (For Frontline Ph+ ALL or CML-LBC Cohort: Age 60 years or older)

4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of < or = 2

5. The following baseline laboratory data: ---Serum bilirubin < or = 2.0 mg/dl ---Serum
creatinine < or = 2.0 mg/dl ---Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) < or = 3 x upper limit of normal (ULN)

6. Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotrophin (beta-hCG) pregnancy test result within 14 days prior to the
first dose of study drugs and must agree to use one of the following effective
contraception methods during the study and for 30 days following the last dose of
study drug. Effective methods of birth control include: --birth control pills,
--shots, --implants (placed under the skin by a health care provider) or patches
(placed on the skin); --Intrauterine devices (IUDs); --condom or occlusive cap
(diaphragm or cervical/vault caps) used with spermicide. Females of non-childbearing
potential are those who are postmenopausal greater than 1 year or who have had a
bilateral tubal ligation or hysterectomy.

7. Males who have partners of childbearing potential must agree to use an effective
contraceptive method during the study and for 30 days following the last dose of study
drug.

8. Patients or their legally authorized representative must provide written informed
consent.

Exclusion Criteria:

1. History of another primary invasive malignancy that has not been definitively treated
or in remission for at least 2 years. Patients with non-melanoma skin cancers or with
carcinomas in situ are eligible regardless of the time from diagnosis (including
concomitant diagnoses).

2. Patients with active unstable angina, concomitant clinically significant active
arrhythmias, myocardial infarction within 6 months, or congestive heart failure New
York Heart Association Class III-IV. Patients with a cardiac ejection fraction (as
measured by either MUGA or echocardiogram) < 40% are excluded.

3. Known evidence of active cerebral/meningeal disease. Patients may have history of CNS
leukemic involvement if definitively treated with prior therapy and no evidence of
active disease (defined as > or = 2 consecutive spinal fluid assessments with no
evidence of disease) at that time of registration.

4. Previous treatment with any anti-CD22 directed therapy

5. Patients with previous allogeneic stem cell transplant (SCT) if they meet either of
the following criteria: ---- < 100 days from allogeneic SCT ---- Active acute or
chronic graft-versus-host disease (GvHD), or ---- Receiving immunosuppressive therapy
as treatment for GvHD within the last 7 days

6. Patients with uncontrolled active infections (viral, bacterial, or fungal) are not
eligible

7. Active hepatitis B or C infection, or known seropositivity for HIV

8. Patients with liver cirrhosis or other serious active liver disease or with suspected
alcohol abuse

9. History of autoimmune diseases (such as systemic lupus erythematosus (SLE), Wegener's,
Wegener's granulomatosis, polyarteritis nodosa) Note: Prior autoimmune diseases are
allowed as long as clinically stable.

10. Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the
start of study drugs with the following exceptions: a. To reduce the circulating
lymphoblast count or palliation: steroids, hydroxyurea. No washout necessary for these
agents. b. For ALL maintenance/CML treatment: mercaptopurine, methotrexate,
vincristine, single-agent, single-dose fo cytarabine and/or tyrosine kinase
inhibitors. These agents should be discontinued at least 48 hours prior to start of
study drugs. (Note: the interval of time from last dose of any approved TKI to start
of protocol treatment is 48 hours regardless of the indication for treatment with the
TKI.)

11. Patients who have not recovered from acute non hematologic toxicity (to < or = Grade
1) of all previous therapy prior to enrollment

12. Females who are pregnant or lactating

13. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that in the opinion of the investigator may increase the risk associated
with study participation or investigational product administration or may interfere
with the interpretation of study results and/or would make the patient inappropriate
for enrollment into this study.

14. Patients previously exposed to bosutinib are eligible unless they carry T315I

15. Patients with T315I mutations will be excluded (This criteria is not applicable for
the frontline Ph+ ALL or CML-LBC cohort)