Trial Information

Phase II Study of Methotrexate, Vincristine, Pegylated L-asparaginase and Dexamethasone (MOAD) in Acute Lymphoblastic Leukemia (ALL) Salvage

The Study Drugs:

Methotrexate is designed to disrupt cells from making and repairing DNA (the genetic
material of cells) and "copying" themselves.

Vincristine is designed to interfere with the multiplication of cancer cells, which may slow
or stop their growth and spread throughout the body. This may cause the cancer cells to
die.

Pegylated-L-asparaginase is designed to get rid of an important building block of proteins
in leukemia cells.

Dexamethasone is a steroid that causes the leukemia cells to breakdown.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive methotrexate
through a needle in your vein on Days 1 and 15 (+/- 2 days) over 2 hours. You will receive
vincristine by vein on Days 1, 8 and 15 (+/- 2 days) over 30 minutes. You will receive
pegylated-L-asparaginase by vein on Days 2 and 16 (+/- 2 days) over about 2 hours. You will
receive dexamethasone by vein over about 30 minutes or by mouth on Days 1-4 and 15-18 (+/- 2
days). If leukemia cells have a protein called CD20, you will also receive rituximab by vein
on Days 1 and 15 of Cycles 1-4 (+/- 2 days) over about 2-8 hours.

Each cycle will be at least 28 days.

If you have Philadelphia positive ALL, you may continue to receive a tyrosine kinase
inhibitor (TKI). Examples of TKIs include Imatinib, Dasatinib, and Nilotinib. If you are not
taking a TKI, you may begin taking a TKI. Your doctor will describe treatment with TKIs
with you in more detail.

Once your blood counts improve and your leukemia is under control your doctor may decide to
continue on treatment every 4-6 weeks. If your leukemia is not under control after the first
cycle, your doctor may decide to start the next cycle without your blood counts improving.

Study Visits:

During Cycle 1, blood (about 2 teaspoons) will be drawn at least 1 time each week for
routine tests. If the doctor thinks it is necessary, you may be asked to have additional
blood drawn.

Between Days 14-28 of Cycle 1, you will have a bone marrow aspirate to check the status of
the disease. This test may be delayed or repeated if your doctor does not think you are in
remission.

Since pegylated-L-asparaginase can cause problems with blood clotting and inflammation of
the pancreas, on Days 2 and 16 of All cycles, blood (about 2 teaspoons) will be drawn to
check how well your blood clots and to check the health of your pancreas.

During Cycles 2- 6, blood (about 2 teaspoons) will be drawn for routine tests at least 2
times each month.

If the doctor thinks it is necessary, you may have a bone marrow aspirate to check the
status of the disease.

Length of Study:

You may receive the study drugs for up to 6 cycles. You will be taken off study early if the
disease gets worse, you experience intolerable side effects, or your doctor thinks that it
is no longer in your best interest to receive the study drug(s).

This is an investigational study. Methotrexate, pegylated-L-asparaginase, and vincristine
are all FDA approved for use in ALL. Dexamethasone is FDA approved as a steroid and
steroids are traditionally an important part of treatment of leukemia. Rituximab is FDA
approved for the treatment of non-Hodgkin's lymphoma. The combination of all these drugs is
investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.