Trial Information

Phase II Randomized Study Evaluating the Addition of Rituximab to the Preparative Regimen of Etoposide and Total Body Irradiation in Acute Lymphoblastic Leukemia

Disease relapse and GVHD are 2 factors that significantly impact survival in ALL patients
who receive SCT. GVHD occurs when donor cells (graft) attack the stem cell recipient's
(host's) cells. The term "acute" refers to the time it takes for the GVHD to appear after
the transplant. This time frame is usually within the first 100 days after the transplant.
GVHD occurs in up to 50% of patients who receive a transplant.

Etoposide is a traditional chemotherapy drug that is designed to interfere with the
production of cancer cells at the DNA and RNA level. Total body irradiation (TBI) uses low
level radiation to also interfere with the production of cancer cells at the DNA and RNA
level. The combination of etoposide and TBI is a standard transplant conditioning therapy
used for ALL patients. Rituximab is a monoclonal antibody that is designed to work against
cells that express the antigen CD20. In addition, some studies suggest that it may decrease
the risk of GVHD.

Before you can start treatment on this study, you will have what are called "screening
tests". These tests will help the doctor decide if you are eligible to take part in the
study. You will have a complete medical history and physical exam, including routine blood
(2-3 teaspoons) and urine tests. You will have a chest x-ray, heart scan (echocardiogram or
MUGA scan (Multi Gated Acquisition Scan)), lung function test, and a bone marrow biopsy with
aspirate to evaluate the status of your disease before transplant. To collect a bone marrow
biopsy and aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small
amount of bone marrow and bone is withdrawn through a large needle. A bone marrow core (a
solid piece from the bone marrow) is also collected through a hollow needle inserted into
the hip bone. Women who are able to have children must have a negative blood pregnancy
test.

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the toss of a coin) to one of 2 treatment groups. Participants in one group will
receive etoposide and TBI before their transplant. Participants in the other group will
receive etoposide, TBI, and rituximab before their transplant. There is an equal chance of
being assigned to either group. You will receive treatment on this study as an inpatient.

On the 1st day of hospitalization, you will receive fluids by vein through a central venous
catheter (a plastic tube inserted into a large vein under your collar bone). You will
receive TBI, once a day for the next 4 days. During TBI, you will lie flat on a table and
receive radiation beams to all parts of the body, with shielding over certain parts of the
body. On the following day, you will receive etoposide through the catheter over 4 hours.
You will then have 2 days of rest, followed by your transplant of stem cells. The stem
cells will be infused into your vein. The infusion can last from 30 minutes to several
hours.

If you are assigned to the rituximab group, you will also receive rituximab once a week for
4 weeks by vein over 4-8 hours. The first dose will be given on the first day you receive
etoposide. If you are receiving a mismatched-related allogeneic stem cell transplant or an
unrelated allogeneic stem cell transplant, you will also receive Thymoglobulin by vein on
the 3 days before the stem cell infusion. This is given to decrease the risk of GVHD and
graft rejection in mismatched transplants.

In addition, you may receive a supportive care drug called palifermin (Kepivance®), which
is a human keratinocyte growth factor (KGF) produced by recombinant DNA technology in E.
coli. Its use has been shown to decrease mucositis resulting from high dose chemotherapy
used in stem cell transplantation. You may receive palifermin for 3 days before starting
radiation therapy, and for 2 days beginning on the day of your stem cell infusion. You may
not receive palifermin but you will still receive transplant.

After you blood counts have normalized following your stem cell transplant, you will start
taking imatinib mesylate by mouth only if your disease has the Philadelphia chromosome (Ph+
ALL). Approximately 25-30% of adults with ALL harbor the Philadelphia chromosome. You will
take it once a day until 1 year after your transplant. Imatinib mesylate should be taken
with a meal and a glass of water, preferably in the morning. The dose will be gradually
increased as long as you don't experience severe side effects. If severe side effects occur,
imatinib will be stopped, either temporarily or permanently.

You will receive several other medications to help the treatment work and to help decrease
the risk of infections while your immune system is weak. Tacrolimus and methotrexate will
be given to decrease the risk of GVHD. The tacrolimus will be started on the day before the
transplant and will continue for up to 6 months. Tacrolimus is given by vein at first and
then by mouth when you are able to eat. Methotrexate is given by vein on Days 1, 3, 6, and
11 after the transplant.

Sulfamethoxazole (Bactrim) or pentamidine will be given to fight bacteria. Bactrim is given
by mouth when your blood counts are good. Pentamidine is given by vein when the counts are
low. Acyclovir will be given at first by vein and then Valtrex (valacyclovir) will be given
by mouth to decrease the risk of viral infections. Both of these will be given as per
standard of care. Granulocyte colony-stimulating factor (G-CSF) will be given to help the
new bone marrow grow. It is given as an injection under the skin after the transplant. It
will continue until the white blood cells reach an acceptable level. These are all routine
supportive medications used during bone marrow transplantation. Overall, some of these
drugs will be given for as long as 6 months or possibly longer. Other medications may be
necessary. If you are allergic to some of these drugs, changes will be made.

You will be in the hospital for about 3-4 weeks. You will have checkups every day until you
are discharged from the hospital. You will then be seen in the outpatient clinic at least 3
times a week until your blood counts improve. You will be seen by your doctor at least every
week until 100 days after the bone marrow transplant. You must stay in Houston during this
time. After 100 days, you will be required to return to Houston every 3 months for tests and
evaluation over the next 2 years. At these visits, you will have blood (about 2-3
teaspoons) collected for routine tests. You will also have a bone marrow biopsy.

Some participants may need to receive spinal taps with chemotherapy (methotrexate or
cytarabine given through the spine) several times over the year after transplantation. This
is only for patients with a previous clinical history of leukemic involvement of the brain
or high risk of developing leukemia relapse in the brain. The spinal tap is performed in
the clinic. If you are one of these participants, you will be given local anesthetic at the
lower back site where a small needle will be inserted in the space between 2 spinal bones.
A small amount of fluid that bathes the brain (cerebrospinal fluid) will be removed for
testing, and a small amount of chemotherapy will be given.

This is an investigational study. The FDA has approved all of the drugs used in this study
for use in stem cell transplantation. However, their use together in this study is
experimental. Up to 80 patients will take part in this study. All will be enrolled at UT MD
Anderson Cancer Center.