Trial Information

A Randomized Study of Once Daily IV Busulfan With Fludarabine With Hemopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA, and is commonly
used in stem cell transplantation. Fludarabine is an antimetabolite drug which has
anti-leukemia and immunosuppressive effects.

If you are eligible to take part in this study, you will be randomly assigned (as in the
toss of a coin) to 1 of 2 study groups. One group will receive a fixed dose of busulfan,
while the other group will receive an adjusted dose of busulfan based on blood levels of the
drug. Both groups will receive fludarabine treatment as well as a stem cell transplant.

Patients in the adjusted-dose group will first receive a low-level "test" dose of busulfan
to check how their blood levels change over time; this information will be used to decide
the next dose needed to reach the target blood level that matches your body size. Patients
in the fixed-dose group will receive a fixed dose of busulfan without the test dose. If
you are assigned to the fixed-dose group, this measurement will only affect your dose level
if you have an unusually high or low drug level in your blood. Patients in both groups will
have a total of about 20 teaspoons (less than 7 tablespoons) of blood drawn over time to
check their busulfan blood levels following one or more of the busulfan treatments.

About 11 samples of blood will be drawn to check your blood levels of busulfan over time
following the test dose and the first high-dose busulfan treatment; each sample is about 1
teaspoon of blood. A 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 these blood level tests to
be performed for technical or scheduling reasons, you will receive the standard fixed dose.

Both groups of patients receive fludarabine through a central venous catheter (CVC--a small
tube inserted into one of your major veins, usually in the chest or shoulder blade) over 1
hour, once a day, for 4 days. After each dose of fludarabine, the high-dose Busulfan will
be infused through the CVC over 3 hours. These drugs are given to try to kill malignant
cells and suppress your immune system in order to reduce the risk of stem cell transplant
rejection. If you are going to be receiving a transplant from an HLA-type-nonidentical or
unrelated donor, you will also receive Thymoglobulin (ATG) over 4 hours on the 3 days prior
to the transplant to further suppress your immune system.

After 2 days of rest, the allogeneic stem cells (bone marrow or peripheral blood stem cells)
will then be given intravenously (IV--through a needle in your vein). You will receive the
drug G-CSF (Neupogen) as an injection under the skin daily starting 1 week after the
transplant until your blood cell levels return to normal.

Patients usually remain in the hospital for about 4 weeks after stem cell transplantation.
After you are released from the hospital, you will continue as an outpatient in the hospital
area to be monitored for infections and transplant-related complications for a minimum of
100 days after the transplant.

Patients who previously had leukemia involvement in the nervous system may need to receive
spinal taps, with injection of cytosine arabinoside and hydrocortisone, several times over
the year after transplantation to try to keep the leukemia from coming back.

You will undergo blood tests and bone marrow biopsies at 3, 6, and 12 months after the
transplant, to check if the disease is in remission. Your health status will be followed
along with their local physician to find out if the leukemia or myelodysplastic syndrome
comes back, as well as to check the length of your survival.

This is an investigational study. All of the drugs used in this study are approved by the
FDA for treatment of cancer. Up to 230 patients will take part in this study. All will be
enrolled at MD Anderson.