Trial Information

Clofarabine, Gemcitabine and Busulfan Followed by Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)

Study Drug Administration:

On a day between Day -15 and -8 (between 15 and 8 days before you receive the stem cell
transplant), you will receive a low-level "test" dose of busulfan by vein over about 1 hour.
You may receive the test dose before Day -8 as an outpatient in the clinic, or on Day -8 as
an inpatient in the hospital.

Blood (about 1 teaspoon each time) will then be drawn for pharmacokinetic (PK) testing up to
11 times over the 11 hours after the busulfan dose test dose. PK testing measures the
amount of study drug in the body at different time points, and in this case will be used to
figure out what your dose of busulfan should be. The study staff will tell you more about
this PK testing schedule. The PK testing will help the doctor decide your dose of busulfan
for Days -6 through -3.

A heparin lock line will be placed in your vein before the PK testing begins to lower the
number of needle sticks needed for these draws. If for any reason it is not possible for
the PK tests to be performed, you will receive the standard dose of busulfan.

On Day -9 or Day -7, you will be admitted to the hospital and given fluids by vein to
hydrate you.

On Days -6 and -4, you will receive gemcitabine by vein over 10-25 minutes. The dose you
receive will be based on when you join this study. Up to 4 dose levels of gemcitabine will
be tested. Up to 3 participants will be enrolled at each dose level. The first group of
participants will receive the lowest dose level. Each new group will receive a higher dose
than the group before it, if no intolerable side effects were seen. This will continue
until the highest tolerable dose of gemcitabine is found. Once the highest dose is found,
additional participants will be enrolled at that dose. The number of patients in this group
will depend on how many have been enrolled in the other groups.

Each day on Days -6 through Day -3, you will receive clofarabine by vein over 1 hour
followed by your body-specific dose of busulfan by vein over 3 hours. If for any reason you
could not have the PK tests performed, you will receive the standard busulfan dose on these
days.

On Day -3 through Day -1, if your stem cell donor is not related to you, you will receive
antithymocyte globulin (ATG) by vein over 4 hours each day. ATG is designed to weaken your
immune system in order to lower the risk that your body will reject the transplant.

Beginning on Day -2, you will receive tacrolimus over 24 hours every day until you are able
to take it by mouth. Tacrolimus is designed to weaken the immune system and lower the risk
of graft-versus-host-disease (GVHD - a reaction of the donor's immune cells against your
body). Once you are able to take tacrolimus by mouth, you will take it every day for about
6 months, or until the doctor thinks it is safe to stop taking.

On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere
from about 30 minutes to several hours.

On Days 1, 3, 6, and 11, you will receive methotrexate by vein over about 15 minutes.
Methotrexate is also designed to weaken the immune system and lower the risk of GVHD.

Starting 1 week after the transplant, you will receive filgrastim (G-CSF) as an injection
under the skin 1 time each day until your blood cell levels return to normal.

You may be given other 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.

Study Visits:

On a day between Day -15 and Day -8, and then on Day -5 and Day -3 (before the busulfan test
dose, and then a day after the first and second dose of gemcitabine, for a total of 3
times), blood (about 2 teaspoons) will be drawn for tests to check the effect of the study
drugs on the DNA (genetic material) of blood cells.

About 4 weeks after the transplant:

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

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

- You will be checked for possible reactions to the study treatment, including GVHD.

- Blood (about 4 tablespoons) will be drawn for routine tests, to see how the transplant
has taken, and to check the status of the disease.

Length of Treatment:

You will be on study for about 2 years. You will be taken off study early if you have graft
failure (the transplant does not "take"), if the disease comes back and needs another
treatment, if you cannot follow the study directions, if your study doctor think it is in
your best interest, or if you want to leave the study.

You must talk to the study doctor if you want to leave the study early. 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, because your blood cell counts will be dangerously low.

Follow-Up:

About 3, 6, and 12 months after the transplant, and then every 6 months for 1 more year:

- You will have a physical exam.

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

- You will be checked for possible reactions to your treatment, including GVHD.

- Blood (about 4 tablespoons) will be drawn for routine tests, to see how well the
transplant has taken, and to check the status of the disease.

- At any point that your doctor thinks they are needed, you will have a bone marrow
aspiration and computed tomography (CT) scans to check the status of the disease. To
collect a bone marrow aspirate, 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.

The study staff will also stay in contact with your local doctor to find out if the disease
comes back and to check how you are doing.

This is an investigational study. Gemcitabine 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. It is investigational to test
for the best dose of gemcitabine that can be given with busulfan and clofarabine to help
prevent the disease from coming back.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.