Trial Information

Azacitidine Maintenance Therapy After Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia (CML)

Study Drug:

Azacitidine is designed to block genes in cancer cells that stop the function of the
tumor-fighting genes. By blocking the "bad" genes, the tumor-fighting genes may be able to
work better.

Study Drug Administration and Procedures before the Stem Cell Transplant:

If you are found to be eligible to take part in this study, you will be given chemotherapy
before the transplant of donor cells. The chemotherapy is designed to kill leukemia cells
and will also block your body's ability to reject the donor cells that will be given to you
during the transplant. You will receive the chemotherapy on the days before the transplant.
You will receive the transplant on Day 0.

This low-level test dose of busulfan is to check how fast busulfan is processed by your body
and cleared from your blood. This information will help the doctor decide the dose of
busulfan you will receive. You may receive the busulfan test dose as an outpatient during
the week before you are admitted to the hospital or as an inpatient on Day -8 (8 days before
your stem cell transplant).

About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic
(PK) testing. PK testing measures the amount of study drug in the body at different time
points. These blood samples will be drawn at various times before you receive busulfan and
over the next 11 hours. These blood draws will be repeated again on the first day of
high-dose busulfan treatment (Day -5).

A heparin lock line (small IV 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 or scheduling reasons, you will receive the standard fixed dose of
busulfan.

On Days -5 through -2, you will receive fludarabine by vein over 1 hour, then busulfan by
vein over 3 hours.

If you are going to be receiving a transplant from an unrelated donor, or if you have a
donor that is mismatched, you will also receive antithymocyte globulin (ATG) by vein over 4
hours on the 3 days before the transplant. This drug is designed to further weaken your
immune system to reduce the risk of rejecting of the transplant.

You will receive azacitidine as an injection under the skin once a day over 5 days in a row,
starting about 5 weeks after the transplant. This may be repeated once a month for up to 4
months after the transplant. You will have about 23 days of "rest" between each cycle of
treatment (a cycle is the period of 28 days). If intolerable side effects occur, treatment
with azacitidine may be interrupted or stopped altogether.

Stem Cell Transplant:

After the blood-forming cells are collected from the donor, they will be given to you by
vein. You will be given standard drugs to help decrease the risk of side effects. You may
ask the study staff for information about how the drugs are given and their risks.

Drugs to Prevent Infections:

You will receive several drugs to help the stem cell transplant work and to help decrease
the risks of infections while your immune system is weak. Tacrolimus and methotrexate will
be given to decrease the risk of graft-versus-host disease (GVHD), a problem that may occur
if the donor's immune cells fight your body.

- Tacrolimus will be started 2 days before the transplant and will continue for as long
as your doctor thinks is necessary. This is usually 3-12 months, but may be longer if
you develop GVHD. Tacrolimus is given by vein non-stop until you are able to eat. Once
you can eat, it will be given by mouth.

- Methotrexate is given by vein over about 15-30 minutes on Days 1, 3, 6, and 11.

Several drugs will also be given to decrease the risk of other infections. Some of these
antibiotics are given by vein, and some are given as pills. The length of time that you will
take the antibiotics will vary. Your doctor will describe this to you in more detail.

Study Drug Administration after the Stem Cell Transplant:

You will receive azacitidine as an injection under the skin once a day over 5 days in a row,
starting about 5 weeks after the transplant. This may be repeated once a month for up to 4
months after the transplant. You will have about 23 days of "rest" between each cycle of
treatment (a cycle is the period of 28 days). If intolerable side effects occur, treatment
with azacitidine may be interrupted or stopped altogether.

Study Visits:

You will be in the hospital for about 3-4 weeks after the transplant. You will have
check-ups every day until you leave the hospital. After you leave, the number of study
visits will vary, depending on your condition.

You will have bone marrow aspirations collected before chemotherapy, around 1, 6, and 12
months after the transplant. To collect a bone marrow aspirate, an area of the hip bone is
numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large
needle. The bone marrow samples will be used to check the status of the disease and to learn
the way azacitidine works.

Blood (about 2 teaspoons each time) will be drawn to learn about patterns of a process
called methylation. Methylation is a process by which the body may turn "on and off" certain
genes. Blood will be drawn at the following times:

- At baseline.

- Before the stem cell transplant (Day 0).

- Six (6), 9, and 12 months after the transplant.

- Before you receive your first dose of azacitidine (Day 1 of each cycle).

- After you receive the last dose of azacitidine (Day 5 of each cycle).

Blood (about 8 teaspoons each time) will be drawn to learn about the body's immune system
recovery, at the following times:

- Cycle 1- Day 1

- Cycle 1 - Day 14

- Cycle 3 - Day 1

Length of Study:

You will remain on study for up to 1 year. You may be taken off study early if the disease
gets worse or intolerable side effects occur.

This is an investigational study. Azacitidine is FDA approved and commercially available
in patients with myelodysplastic syndrome. Its use in patients with CML is investigational.
All other drugs used in this study are FDA approved and commercially available.

Up to 57 patients will take part in this study. All will be enrolled at MD Anderson.