Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)

Inclusion Criteria:

1. Diagnosis of one of the following: a) Patients >/= 60 years of age with previously
untreated Ph-positive ALL [either t(9;22) and/or BCR-ABL positive] (includes patients
initiated on first course of therapy before cytogenetics known) or with lymphoid
accelerated or blast phase CML. These patients could have received one or two courses
of chemotherapy with or without other TKIs and still eligible. Patients < 60 years of
age may be enrolled if they are considered unfit for intensive chemotherapy: i) If
they achieved CR, they are assessable only for event-free and overall survival; OR ii)
If they failed to achieve CR, they are assessable for CR, event-free, and overall
survival;

2. Continued from #1: Diagnosis of one of the following: b) Patients >/= 18 years of age
with relapsed / refractory Ph-positive ALL or with previously treated lymphoid
accelerated or blast phase CML

3. Performance status
4. Adequate liver function as defined by the following criteria: a) Total serum bilirubin
aminotransferase (ALT)
5. Adequate pancreatic function as defined by the following criteria: a) Serum lipase and
amylase
6. For females of childbearing potential, a negative urine pregnancy test must be
documented

7. Female patients who: Are postmenopausal for at least 1 year before the screening
visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to
practice 2 effective methods of contraception, at the same time, from the time of
signing the informed consent through 4 months after the last dose of study drug, OR
agree to completely abstain from heterosexual intercourse

8. Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: Agree
to practice effective barrier contraception during the entire study treatment period
and through 4 months after the last dose of study drug, OR Agree to completely abstain
from heterosexual intercourse

9. Adequate cardiac function as assessed clinically by history and physical examination

10. Signed informed consent

Exclusion Criteria:

1. Active serious infection not controlled by oral or intravenous antibiotics.

2. History of acute pancreatitis within 1 year of study or history of chronic
pancreatitis

3. History of alcohol abuse

4. Uncontrolled hypertriglyceridemia (triglycerides > 450mg/dL)

5. Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or
squamous cell carcinoma) that in the investigator's opinion will shorten survival to
less than 1 year.

6. Active Grade III-V cardiac failure as defined by the New York Heart Association
Criteria.

7. Uncontrolled, or active cardiovascular disease, specifically including, but not
restricted to: Myocardial infarction (MI), stroke, or revascularization within 3
months; Unstable angina or transient ischemic attack; Congestive heart failure prior
to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of
normal per local institutional standards prior to enrollment; Diagnosed or suspected
congenital long QT syndrome; Clinically significant atrial or ventricular arrhythmias
(such as atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or
Torsades de pointes) as determined by the treating physician; Prolonged QTc interval
on pre-entry electrocardiogram (> 470 msec) unless corrected after electrolyte
replacement;

8. Continued from #7 Uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to: Significant venous or arterial thromboembolism
including deep venous thrombosis or pulmonary embolism. Patients with a history of
treated prior superficial or catheter associated will not be considered as significant
embolism and after discussion with PI will not be excluded from eligibility;
Uncontrolled hypertension (diastolic blood pressure >90mmHg; systolic >140mmHg).
Patients with hypertension should be under treatment on study entry to effect blood
pressure control

9. Taking any medications or herbal supplements that are known to be strong inhibitors of
CYP3A4 within at least 14 days or 5 half-lives before the first dose of ponatinib in
patients with newly diagnosed only.

10. History or presence of clinically relevant CNS pathology such as epilepsy, childhood
or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia,
Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
Patients with active CNS leukemia will NOT be excluded

11. Current autoimmune disease or history of autoimmune disease with potential CNS
involvement

12. Treatment with any investigational antileukemic agents or chemotherapy agents in the
last 7 days before study entry, unless full recovery from side effects has occurred or
patient has rapidly progressive disease judged to be life-threatening by the
investigator.

13. Pregnant and lactating women will not be eligible; women of childbearing potential
should have a negative pregnancy test prior to entering on the study and be willing to
practice methods of contraception. Women do not have childbearing potential if they
have had a hysterectomy or are postmenopausal without menses for 12 months. In
addition, men enrolled on this study should understand the risks to any sexual partner
of childbearing potential and should practice an effective method of birth control.

14. History of significant bleeding disorder unrelated to cancer, including: Diagnosed
congenital bleeding disorders (e.g., von Willebrand's disease); Diagnosed acquired
bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)

15. Patients with documented significant pleural or pericardial effusions unless they are
thought to be secondary to their leukemia