Trial Information

Randomized Phase II Study of Timed Sequential Busulfan in Combination With Fludarabine in Allogeneic Stem Cell Transplantation

Central Venous Catheter:

If you choose to take part in this study, the chemotherapy, some of the other drugs in this
study, and the stem cell transplant will be given by vein through your central venous
catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a
large vein while you are under local anesthesia. Blood samples will also be drawn through
your CVC. The CVC will remain in your body during treatment. Your doctor will explain this
procedure to you in more detail, and you will be required to sign a separate consent form.

Study Groups:

You will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups:

- Group 1 will receive fludarabine and busulfan.

- Group 2 will receive fludarabine and a higher dose of busulfan than Group 1.

Both groups will have a stem cell transplant. The stem cells will be given by vein. The
cells will travel to your bone marrow where they are designed to make healthy, new blood
cells after several weeks.

For a stem cell transplant, the days before you receive your stem cells are called minus
days. The day you receive the stem cells is called Day 0. The days after you receive the
stem cells are called plus days.

Study Drug Administration and Procedures:

Both groups will receive a dose of busulfan by vein over about 3 hours on Day -13 and Day
-12. With the Day -13 busulfan infusion, about 11 samples of blood (about 1-2 teaspoons
each time) will be drawn for pharmacokinetic (PK) testing at various time points before and
after you receive your first dose of busulfan. The study staff will tell you the blood
testing schedule. PK testing measures the amount of study drug in the body at different
time points. The PK testing will help the doctor decide your dose of busulfan for Days -6
through -3. If needed, PK blood testing may also be done on Day -6 during your dose of
Busulfan. You may receive the Day -13 and Day -12 busulfan dose either as an outpatient in
the clinic or as an inpatient in the hospital.

A heparin lock line 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
reasons, you will be taken off study and receive the standard fixed dose of busulfan.

On Days -13 and -12, you will receive busulfan by vein over 3 hours.

On Days -11 through -7, you will rest.

On Days -6 through -3, you will receive fludarabine by vein over 1 hour, then busulfan by
vein over 3 hours.

On Days -2 and -1, you will rest.

On Day 0, you will receive the stem cell transplant by vein.

After the transplant, you will receive tacrolimus, methotrexate, or other drugs to weaken
the immune system in the standard manner to lower the risk of graft-vs-host disease (GVHD),
a reaction of the donor's immune cells against the recipient's body.

You will receive tacrolimus by vein as a nonstop infusion until you are able to take it by
mouth to help lower the risk of GVHD. You will then take tacrolimus by mouth 2 times a day
for about 3 months. After that, your tacrolimus dose may be lowered if you do not have
GVHD. Your doctor will discuss this with you. On Days 1, 3, and 6, if your stem cells are
from a related or matched unrelated donor, you will receive methotrexate over 30 minutes
each day by vein to help lower the risk of GVHD. Participants receiving a matched unrelated
donor will also receive methotrexate on Day 11 after the transplant.

You will receive filgrastim as an injection under the skin 1 time a day, starting 1 week
after the transplant, until your blood cell levels return to normal. Filgrastim is designed
to help with the growth of white blood cells.

Study Testing:

While you are in the hospital, you will be checked for any side effects as part of your
standard of care. Blood (about 2 teaspoons) will be drawn every day to check for side
effects, for routine tests, to check your blood counts, kidney and liver function, and to
check for infections.

As part of standard care, you will remain in the hospital for about 3-4 weeks after the
transplant. After you are sent home from the hospital, you must remain in the Houston area
to be checked for infections and other transplant side effects until about 3 months after
transplant. During this time, you will return to the clinic at least 1 time each week. The
following tests and procedures will be performed:

- You will be asked about how you are feeling and about any side effects you may be
having.

- Blood (about 2 teaspoons) will be drawn for routine tests.

About 1, 3, 6, and 12 months after the transplant:

- You will have a physical exam, including measurement of your vital signs (blood
pressure, heart rate, temperature, and breathing rate).

- You will be asked about how you are feeling and about any side effects you may be
having.

- Blood (about 2 teaspoons) will be drawn to see how well the transplant has "taken."

- You will have a bone marrow aspiration to check the status of the disease, if your
doctor thinks it is needed. To collect a bone marrow aspiration, an area of the hip or
other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn
through a large needle.

Length of Study:

You will be taken off study 3 years after the end of treatment. You may be taken off study
early if the disease gets worse, if you have any intolerable side effects, of if you are
unable to follow study directions.

You should talk to the study doctor if you want to leave the study early. If you are taken
off study early, you still may need to return for routine follow-up visits after the
transplant, if your transplant doctor decides it is needed.

It may be life-threatening to leave the study after you have begun to receive the study
drugs but before you receive the stem cells.

This is an investigational study. Busulfan and fludarabine are both FDA approved and
commercially available. The investigational part of this study is the addition of 2 more
doses of busulfan and the random assignment to a total dose of busulfan.

Up to 100 patients will take part in this study. All will be enrolled at MD Anderson.