Trial Information

Autologous CD19 Specific T-cell Infusion in Patients With B-cell Chronic Lymphocytic Leukemia (B-CLL)

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of genetically changed T cells, based on when you joined this study. Up to 4 dose
levels of T cells 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 of than the group before it, if no intolerable side effects were seen.
This will continue until the highest tolerable dose of T cells is found.

All participants will receive the same dose of chemotherapy.

T Cell Collection (leukapheresis or standard blood draw):

About 30 days after you have completed the screening tests, you will have a leukapheresis
performed at the Apheresis Clinic at MD Anderson.

Before the leukapheresis:

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

- Your medical history will be recorded.

- Blood (about 4 tablespoons) will be drawn for routine tests and to measure levels of
certain proteins.

A leukapheresis is a procedure used to remove blood from the body so that specific blood
cells, such as T cells, can be collected. After the specific cells have been collected, the
remaining blood is returned to the body.

To perform a leukapheresis, blood will be drawn through a needle in a vein in one arm, then
passed though a machine to collect white blood cells, and then the remaining blood will be
returned back to you through a needle in a vein in the other arm. The procedure will take
about 3 hours to complete.

If certain types of unwanted T cells are growing too much, an investigational device called
a CliniMACS® system will be used to filter out the unwanted T cells using a magnet.

It will take about 7 weeks to modify and grow the necessary number of genetically modified T
cells in the lab. If researchers are not able to collect enough T cells for your assigned
dose level, you will be taken off study. Other options will be discussed with you by your
doctor

Chemotherapy:

Before you receive the T cell infusion, you will receive your standard chemotherapy with
fludarabine and cyclophosphamide through a catheter (plastic tube) inserted into a large
chest vein or through an intravenous needle (IV) inserted in a vein in your arm.

Fludarabine will be given by vein over 30 minutes daily for 3 days.

Cyclophosphamide will be given by vein over 3 hours daily for 3 days.

Study Tests Before the T cell Infusions:

Within 60 days before the T cell infusions:

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

- Your medical history will be reviewed and any updates will be recorded.

- You will be asked about any side effects that you may have had.

- Blood (about 4 tablespoons) will be drawn for routine tests, tests to measure levels of
certain proteins, and tests to look at your DNA to check the status of the disease.
This blood draw will include a pregnancy test if you are able to become pregnant. To
continue your participation in this study, you cannot be pregnant.

- Mouse protein antibodies are used in the gene transfer process. If your body becomes
immune to these proteins, your body may develop antibodies against the mouse antibodies
(called "human anti-mouse antibodies" or HAMA). Part of the blood sample will be used
to compare against another sample of blood collected after the gene transfer is
complete to check for HAMA.

- Blood (about 4 tablespoons) will be drawn to learn how your body's immune system
responds to the T-cell infusion.

- You will have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan to check
your heart function.

- You will have lung function tests.

- If the study doctor thinks it is needed, you will have a bone marrow biopsy/aspiration
to check the status of the disease. To collect a bone marrow biopsy/aspirate, an area
of the hip or chest bone is numbed with anesthetic, and a small amount of bone and bone
marrow is withdrawn through a large needle.

- If the study doctor thinks it is needed, you will have computed tomography (CT) scans
and/or positron emission tomography (PET) scans to check the status of the disease.

T-cell Infusions (gene transfer):

The T cell infusion will be given in 2 doses by vein, each over about 15-30 minutes. On the
first day of the gene transfer, you will receive 25% of the cells to be sure you tolerate
the infusion. One (1) day later, if you do not have any severe or intolerable side effects
from the first infusion, you will receive the remaining 75% of the cells.

Before the first infusion, you will receive drugs to lower your risk of allergic reaction to
the T cells. Tylenol® (acetaminophen) will be given by mouth and Benadryl® (diphenhydramine)
may be given by mouth or by vein over a few minutes.

During the T cell infusions, your vital signs will be checked every 15 minutes for the first
hour, then every 30 minutes for the second hour, and about every 1 hour after that for as
long as your doctor thinks it is needed.

Study Tests after the T cell infusions:

Within 24 hours before the first and second parts of the T-cell infusion, within 1-3 days
after T-cell infusion, then again at 2 weeks (+/- 3 days), 3 weeks (+/- 3 days), 1 month
(+/- 5 days), 6 months (+/- 14 days), and 12 months (+/- 14 days) after the T-cell
infusions, the following tests and procedures will be performed:

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

- Your medical history will be reviewed and any updates will be recorded.

- You will be asked about any side effects that may have had.

- Blood (about 4 tablespoons) will be drawn for routine tests, tests to measure levels of
certain proteins, and tests to look at your DNA to check the status of the disease.
Part of this blood sample will be used to compare against a sample of blood that was
collected before the gene transfer to check for HAMA (at 3 months after the T cell
infusion only). If you leave the study early for any reason, your blood will be checked
for HAMA at that time.

- Blood (about 4 tablespoons) will be drawn to learn how your body's immune system
responds to the T-cell infusion.

At around 6 and 12 months after the last T-cell infusion, if the study doctor thinks it is
needed you will have CT scans, PET-CT scans, and/or a bone marrow biopsy to check the status
of the disease.

Length of Study:

Your participation on this study will be over after you have completed the last planned
study visit at about 12 months after the last T cell infusion is complete. You may be taken
off study early if the disease gets worse, you experience any intolerable side effects, you
cannot keep your appointments, if your doctor thinks it is in your best interest, or if you
are unable to receive the T-cell infusion(s).

Long-Term Follow-Up Study:

For safety reasons, the U.S. Food and Drug Administration (FDA) requires that patients who
receive stem cells infusions that have been treated with a gene transfer procedure must have
long-term follow-up for at least 15 years after receiving the gene transfer. You will be
asked to sign a separate consent form for a long-term follow-up study Protocol 2006-0676.

This is an investigational study. Fludarabine and cyclophosphamide are commercially
available and FDA approved for the treatment of CLL. The T cell infusion using a gene
transfer procedure is not commercially available or FDA approved. At this time, T cell
infusions using a gene transfer procedure is only being used in research.

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