Trial Information

Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies

Central Venous Catheter Placement:

You will first have a central venous catheter (CVC) placed. 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 procedure to you in more detail, and you will be required to sign a
separate consent form for it.

The chemotherapy, some of the other drugs in this study, and the cord blood transplant will
be given by vein through your CVC. Blood samples will also be drawn through your CVC. The
CVC will remain in your body for about 2-5 months.

Study Plans:

If you agree to take part in this study, your doctor will choose one of the following 2
study plans based on the disease and your age and medical history.

Fludarabine/Clofarabine/Busulfan/Rituximab/Total Body Irradiation:

If you are between 1 and 55 years of age and can receive high-dose chemotherapy, or you are
between 55 and 65 years old and your doctor agrees, you will receive fludarabine,
clofarabine, busulfan, ATG, total body irradiation, and possibly rituximab.

You will receive a test dose of busulfan by vein over 60 minutes as an outpatient, usually
during the week before you are admitted to the hospital. If the test dose cannot be given as
an outpatient, you will be admitted to the hospital on Day -10 for intravenous (IV) fluids
and will receive the busulfan test dose on Day -9. This low-level "test" dose of busulfan is
to check how the level of busulfan in your blood changes over time. This information will be
used to decide the next dose needed to reach the target blood level that matches your body
size.

About 11 samples of blood will be drawn for pharmacokinetic (PK) testing of busulfan. PK
testing measures the amount of study drug in the body at different time points. These blood
samples will be drawn at various timepoints starting before the busulfan infusion and
continuing over about the next 11 hours. The blood samples will be repeated again with the
first day of high-dose busulfan treatment. Each sample will be about 1 teaspoon of blood.
A temporary heparin lock will be placed in your vein to lower the number of needle sticks
needed for these draws. If it is not possible for the PK tests to be performed for
technical or scheduling reasons, you will receive the standard fixed dose of busulfan.

If you will receive the test dose as an outpatient, you will be admitted to the hospital on
Day -8 and will receive fluids by vein. If appropriate for the disease, you will receive
rituximab by vein over 4-6 hours on Day -8.

If you will receive the test dose as an inpatient, you will be admitted on Day -10 and will
receive fluids by vein. If appropriate for the disease, you will receive rituximab by vein
over 4-6 hours on Day -10.

On Days -7 through -4, you will receive fludarabine by vein over 1 hour, clofarabine by vein
over 1 hour, and busulfan by vein over 3 hours. You will receive ATG on Days -4 and -3. On
Day -3, you will receive a single treatment of low-dose total body irradiation. You will
"rest" (not receive chemotherapy drugs) on Days -2 and -1. Day 0 is the day of the cord
blood transplant, so the negative day numbers are used to label the treatment days before
the transplant.

All chemotherapy drugs, fluids, and other drugs that must be given by vein will be infused
through the catheter. Once the back-up cells are collected, all participants will be
admitted to the hospital as indicated by their assigned treatment plan schedule.

Fludarabine/Melphalan:

If your doctor chooses fludarabine and melphalan, you will have the following schedule:

- On Day -6 (6 days before your transplant), you will be admitted to the hospital and
will receive fluids by vein.

- On Days -5, -4, and -3, you will receive fludarabine by vein over 30 minutes.

- On Days -4 and -3, you will receive ATG by vein over 4 hours.

- On Day -2, you will receive fludarabine by vein over 30 minutes and melphalan by vein
over 30 minutes.

- On Day -1, you will not receive any drugs.

- On Day 0, you will receive your cord blood transplant through the CVC.

Supportive Drugs:

Starting on Day -3, you will receive mycophenolate mofetil as a tablet by mouth 2 times a
day. If you are not able to take the tablet by mouth, you will receive MMF by vein over 2
hours 2 times a day. If you do not have GVHD at Day 100 after your cord blood transplant,
the dose of MMF will be gradually lowered. If you have GVHD, MMF may be stopped 7 days
after the GVHD is controlled.

Starting on Day -2, you will receive tacrolimus by vein as a continuous (nonstop) infusion
until you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a
day for about 6 months. After that, your tacrolimus dose may be gradually lowered if you do
not have GVHD. Your doctor will discuss this with you.

Starting on Day 0, you will receive filgrastim (G-CSF) through a needle under the skin 1
time a day every day until your white blood count begins to recover. Filgrastim is designed
to help cells in the bone marrow to divide, which helps raise white blood cells counts more
quickly, lower fever, and decrease the risk of infection.

Study Visits:

At about 1, 3, 6, and 12 months after the transplant:

- You will have a physical exam.

- You will be checked for possible reactions to the transplant and study drugs, including
GVHD.

- Blood (about 4 teaspoons) will be drawn for routine tests, to check for CMV antibodies,
and for genetic tests to learn if the donor's cells have "taken". The routine blood
tests will be repeated as often as the doctor thinks is needed.

- If the doctor thinks it is needed, you will have a bone marrow aspiration to check the
status of the disease.

You will need to stay in the hospital for about 4 weeks. After you leave the hospital, you
will continue as an outpatient in the hospital area, which means you will have to stay close
enough to be able to come back for any visits for about 100 days after the transplant.

Length of Participation:

You will be on study for up to 1 year. You will be taken off study early if the disease
gets worse, if intolerable side effects occur, if the cord blood is infected and cannot be
transplanted, if you are unable to follow study directions, or if your doctor thinks it is
in your best interest.

This is an investigational study. Fucosylation is not an FDA-approved process. It is
currently being used for research purposes only. Fludarabine, busulfan, clofarabine,
melphalan, mycophenolate mofetil, tacrolimus, and rituximab are FDA approved and
commercially available to be given to patients with leukemia or lymphoma having a cord blood
transplant. Total body irradiation is delivered using FDA-approved and commercially
available methods.

Up to 25 patients will be enrolled in this study. All will be enrolled at MD Anderson.