Study of Blinatumomab in Patients With B-cell Lineage Acute Lymphocytic Leukemia With Positive Minimal Residual Disease

Study Drug Administration:

Each study cycle is 6 weeks.

If you are found to be eligible to take part in this study, you will receive blinatumomab by
a central venous catheter (CVC) continuously for Weeks 1-4 of each cycle. A CVC is a sterile
flexible tube that will be placed into a large vein while you are under local anesthesia.
Your doctor will explain this to you in more detail, and you will be required to sign a
separate consent form for this procedure.

During Cycle 1, the blinatumomab infusion will be started in the hospital. You will be in the
hospital for up to 9 nights so that you can be checked for side effects. Your doctor will
decide when you can leave the hospital.

Blinatumomab will be delivered by a small pump, which you will carry with you for the whole
time you receive the drug. You will be given a shoulder or belt bag to hold the pump and
infusion bag. You will be able to wear regular clothes, walk around, and perform daily living
activities. You will be given instructions for taking a shower and other activities. There
will be some things that you should not do, such as go swimming. The study staff will give
you more information on activities you should not do while receiving the drug.

You will need to come to MD Anderson to have the infusion bags changed every 48 hours. The
study staff will let you know when you need to return to the clinic.

You will be given standard drugs, such as dexamethasone, to help decrease the risk of side
effects. You may ask the study staff for information about how the drugs are given and their
risks.

If you have severe side effects, your study doctor may decide to stop treatment permanently
or temporarily. If you recover or if the symptoms have improved, the treatment may be
continued. If the doctor thinks it is needed, you will have a magnetic resonance imaging
(MRI) before you restart treatment.

Length of Study:

You may receive blinatumomab for up to 5 cycles. You will no longer be able to take the study
drug if the disease gets worse, if intolerable side effects occur, or if you are unable to
follow study directions.

You participation on this study will be over after you have completed follow-up.

Study Visits:

At the beginning of every cycle, you will have a physical exam.

One (1) time each week during Cycles 1-5, blood (about 2-3 teaspoons) will be drawn for
routine tests.

During Week 6 of Cycle 1 and then 1 time every cycle after that, you will have a bone marrow
biopsy/aspiration to check the status of the disease.

Follow-Up:

You will be called by the study staff and asked about your health 1 time each month for up to
18 months after all participants have been enrolled in the study. These calls should last
about 5-10 minutes each.

Inclusion Criteria:

1. Patients at least 18 years of age.

2. Patients with B-lineage ALL in hematologic complete remission (CR) with molecular
failure (ie, had never achieved an MRD-negativity status before blinatumomab) or had a
molecular relapse (ie, became MRD positive after having been MRD negative) starting at
any time point after 3 months of frontline therapy. Molecular disease or minimal
residual disease is defined by a value of at least of 1x10^-4 by multicolor flow
cytometry.

3. Patients with B-lineage ALL in at least marrow CR in Salvage 1 and beyond with
molecular failure at any time point after 1 month of salvage therapy are allowed,
including patients who received prior allogeneic stem cell transplantation.

4. Performance status of 0, 1, or 2

5. Adequate organ function with creatinine clearance >/= 30 ml/minute and bilirubin less
than or equal to 3.0 mg/dL.

6. No active or co-existing malignancy with life expectancy less than 12 months.

7. Patients with Ph+ ALL can be enrolled in CR1 or CR2 and beyond. A TKI will be added at
the discretion of the treating physician. MRD for these patients will be defined by
PCR of 0.1% and above (International Scale).

Exclusion Criteria:

1. Pregnant or nursing women

2. Known to be HIV+

3. Active and uncontrolled disease/infection as judged by the treating physician

4. Unable or unwilling to sign the consent form

5. Active CNS or extramedullary disease

6. Monoclonal antibodies therapy within 2 weeks before study entry

7. Radiotherapy and cancer chemotherapy (except for intrathecal prophylaxis and/or
low-dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate,
steroids) or any investigational drug within 2 weeks before study entry