Trial Information

Azacitidine Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for AML and MDS

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

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 this
study. You will have a complete medical history and physical exam. 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 given chemotherapy,
before the transplant of donor cells. There are 2 major goals to giving this chemotherapy.
One goal is to directly kill leukemic cells. The other goal is to block your ability to
reject the donor cells that will be given to your for the transplantation.

All participants will receive a combination of 3 chemotherapy drugs--gemtuzumab,
fludarabine, and melphalan. In order to receive gemtuzumab, your bone marrow leukemia cells
have to be positive for a marker called "CD33," which is present in the majority of myeloid
leukemias. If your cells are negative for that marker, the chemotherapy you receive will not
include gemtuzumab. Anti-thymocyte globulin (ATG) will be given to patients receiving stem
cells from an unrelated donor, or from a relative that is not fully matched with you.

All chemotherapy drugs are given by vein through a silicone catheter. Gemtuzumab is given
12 days before the transplant (may be given as an outpatient infusion). Fludarabine is given
once a day for 4 days (5-2 days before the transplant), and melphalan is given as a single
dose 2 days before the transplant. If you are receiving ATG, this drug will be given in 3
doses, given 3-1days before the transplant. The transplant day is usually referred to as
"Day 0."

A total of 5 bone marrow biopsies will be collected during the first year after
transplantation--before the start of treatment, around 1 month after transplantation, and
around 4, 9, and 12 months after transplantation. To collect a bone marrow sample, an area
of the hip bone is numbed with anesthetic, and a small amount of bone marrow and bone is
withdrawn through a large needle. The bone marrow samples will be used primarily for disease
status evaluation, but researchers will also use the samples for research on the way
azacitidine works.

Eleven (11) blood samples (2 teaspoons each) will be collected for research purposes during
the 1 year of your participation in this study. Samples will be collected before
chemotherapy, before stem cell transplantation, before and after you receive 5-azacitidine
(for each of the 4 cycles of treatment), and on the third week of the first cycle of
5-azacitidine treatment.

After the blood-forming cells are collected from the donor, they will be given to you by
vein for your transplant. Before the infusion, you will receive medications, such as
steroids and Benadryl (diphenhydramine), to decrease the risk of side effects. These
"premedications" are given by vein usually 30 to 60 minutes before the transplant.

You will receive several medications to help the treatment 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 a variable period of time (e.g., 3-12 months, or longer if
you develop GVHD). Tacrolimus is given by vein at first and then by mouth, when patients
are able to eat. Methotrexate is given by vein 1, 3, and 6 days after transplantation.

Several medications are used for the prevention of infections (potentially caused by fungal,
bacterial, and viral organisms). Some of these antibiotics are given by vein, and some are
given as pills, for variable lengths of time. You will receive medications while you are on
tacrolimus or other medications that may weaken your immune system (such as steroids), in
order to prevent infections, such as pneumonia. These antibiotics may include Bactrim,
Diflucan, or other medications, if necessary.

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 frequency of clinic
visits will vary, depending on your condition. You may need to come to the hospital as often
as daily.

If your first bone marrow examination after transplantation determines that you are in
remission, you will be eligible to receive azacitidine in one of 3 doses. Your dose and
schedule of administration will be decided before you start the treatment. Participants will
be enrolled starting with the smallest dose and moving upwards in terms of dose, if no side
effects are detected. Each participant will have an assigned dose. This dose may be
decreased or may be stopped or may not be given at all if certain side effects develop.

Azacitidine will be given as an injection under the skin once a day over 5 days in a row.
This may be repeated once a month for up to 4 months after the transplant. You will be
assigned to receive the drug for one to four cycles. You will have about 25 days of "rest"
between each cycle of treatment (a cycle is the period of 1 month.). If intolerable side
effects occur, treatment with azacitidine may be interrupted or stopped altogether before
you finish treatment.

While on study, you will need to stay in Houston for up to 5 months after your transplant.
You will then be required to return at 9 and 12 months after the transplant, though the
frequency of the visits may be higher, if thought necessary by your doctor. After 1 year,
your follow-up will continue as is standard of care for your disease.

This is an investigational study. Azacitidine and the other drugs described here are
approved by the FDA. The use of azacitidine after allogeneic transplantation is
experimental.About 90 patients will take part in this study. All will be enrolled at M. D.
Anderson.