Trial Information

Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies

The Study Drugs:

Thiotepa and busulfan are designed to bind to DNA (genetic material of cells), which may
cause cancer cells to die. They are commonly used in stem cell transplants.

Clofarabine is designed to interfere with the growth and development of cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will begin receiving the
study drugs before you receive the stem cell transplant.

On Day -8 (8 days before you receive the stem cell transplant), you will receive thiotepa
through a central venous catheter (CVC) over 2 hours. 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 this procedure.

On Day -7, you will receive busulfan through a CVC. This dose of busulfan is a low level
"test" dose to check how your blood levels change over time. This information will be used
to decide the next dose level of busulfan.

Blood (about 1 teaspoon each time) will be drawn 6-11 times total over Days -7 and -5 for
pharmacokinetic (PK) testing. PK testing measures the amount of busulfan in the body at
different time points. This PK testing will be done to find the dose of busulfan needed for
your body size on the other days that you receive busulfan. A heparin lock line will be
placed in a vein to lower the number of needed sticks performed for draws. If you cannot
have the blood level tests performed for any reason, you will receive the standard busulfan
dose.

On Days -6, -5, -4, and -3, you will receive clofarabine through a CVC over 1 hour.

On Days -5, -4, and -3, you will receive busulfan through a CVC over 3 hours.

On Days -4 and -3 you will also receive antithymocyte globulin (ATG) by vein over 4 hours.
This will help to reduce the risk of your body rejecting the transplant. If your transplant
will involve haploidentical stem cells, you will not receive ATG on Days -4 and -3.

On Days -2 and -1, you will "rest," which means you will not be given any drugs, but your
CVC will remain in place.

Stem Cell Transplant:

On Day 0, you will have an allogeneic or haploidentical stem cell transplant through the
CVC. Allogeneic stem cells come from a donor whose cells closely match your own cells.
Haploidentical stem cells come from a donor whose cells do not match your own cells as
closely, but they are specially processed to help prevent graft versus host disease (GVHD).

Receiving stem cells is similar to receiving a blood transfusion. The time required to
receive the stem cells will depend on the type of cells you are receiving. Receiving cord
blood stem cells can take several minutes. Receiving bone marrow and blood stem cells may
take several hours.

You will receive G-CSF (filgrastim) (which helps to produce white blood cells) as an
injection under the skin once a day, starting 1 week after the transplant, until your blood
cell levels return to normal.

You will receive drugs (mycophenolate mofetil (MMF), tacrolimus and/or methotrexate) to help
prevent side effects, such as GVHD. You will receive methylprednisolone if you develop GVHD.

You will stay in the hospital for about 4 weeks after the stem cell transplantation.

If you had a haploidentical stem cell transplant, on Days 3 and 4 after your stem cell
transplant, you will receive cyclophosphamide through a CVC over 30-60 minutes. Mesna will
be given by vein at the same time you are given each dose of cyclophosphamide, to help
protect your bladder from bleeding.

Study Visits:

Beginning on Day -9, once a day while you are in the hospital:

- You will have a physical exam, including measurements of your vital signs.

- You will be asked if you have had any side effects.

- Blood (about 4 tablespoons) will be drawn to test your blood cell counts. Two (2) times
a week, this blood will be also be used for routine tests.

After you are out of the hospital, 2 times a month until it has been 100 days after the
transplant:

- You will have a physical exam, including measurements of your vital signs and weight.

- You will be asked if you have had any side effects.

- Blood (about 4 tablespoons) will be drawn for routine tests.

About 1, 3, 6, and 12 months after the transplant, blood (about 4 tablespoons) will be drawn
to check the status of the disease. You will also have bone marrow aspirations to check the
status of the disease. You will also have a physical exam.

If the doctor thinks it is necessary, you may have extra tests and procedures.

Length of Study:

You will be on study for about 1 year. You will be taken off study if the disease gets worse
or needs further treatment.

Follow-Up:

If you live close to M. D. Anderson, you will return to the clinical once every several
months for a physical exam. At these visits, blood (about 3 teaspoons) will be drawn for
routine tests.

You and/or your local doctor will be called every several months and asked about your health
status and if the leukemia or MDS has come back.

This is an investigational study. Thiotepa and clofarabine are FDA approved and
commercially available for the treatment of leukemia. Busulfan is FDA approved and
commercially available for use in stem cell transplantation. The combination of thiotepa,
clofarabine, and busulfan together with a stem cell transplant is investigational.

Up to 60 participants will take part in this study. All will be enrolled at M. D. Anderson.