Immune Reconstitution Following Campath Based Therapy

CLL patients often develop weakened immune systems (the cells that help fight against
infections), especially patients who receive treatment with fludarabine or alemtuzumab. This
means these patients are more likely to develop infections. Researchers want to find out if
building up the immune system with specially-activated T-cells can help to lower the chance
of these patients getting infections.

This research involves a certain type of white blood cell in your body called T-cells.
T-cells will be collected from your blood using a process called leukapheresis. During
leukapheresis, your blood is drawn through a needle in your vein, then run through a machine
which separates out your white blood cells, then returns the rest of the blood to your body
through a separate tube in another vein. The T-cells will then be grown in the research
laboratory. In the laboratory, your T-cells will exposed to certain chemicals, which will
help "activate" (turn on) the anti-cancer activity and increase the number of T-cells that
will be given back to you.

Screening Tests:

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 the
study:

- You will have a complete physical exam.

- You may have either a chest x-ray or a computerized tomography (CT) scan if your doctor
thinks it is needed to check for swollen lymph nodes or spleen, which is common in CLL.

- If you have not had a bone marrow biopsy collected in the past 4 months, you will have
a bone marrow sample collected at this time. To collect a bone marrow biopsy, an area
of the hip or chest bone is numbed with anaesthetic, and a small amount of bone marrow
is withdrawn through a large needle.

- Blood (about 3 tablespoons) will be drawn for routine tests and tests of your liver and
kidney function. This routine blood draw will include a pregnancy test for women who
are able to have children. To take part in this study, the pregnancy test must be
negative.

T-Cell Collection:

If you are found to be eligible to take part in this study, you will undergo a leukapheresis
procedure to collect T-cells before starting your chemotherapy schedule. Leukapheresis takes
about 4 hours. First, a needle and plastic tube (line) will be inserted into a vein in each
arm. In some cases, if that is not possible, a central venous catheter (CVC) may be placed
in the vein under your collar bone or in your groin. If a CVC is needed, you will be asked
to sign a separate consent form for that procedure.

A machine is attached to the needles or to the catheter, and blood is withdrawn through 1 of
the needles. The blood then flows through the machine, which removes the needed T-cells from
the blood. The blood is then returned back to you through the CVC or other needle. The
T-cells that are removed are then frozen and stored. These cells will be expanded and
activated in the laboratory and given back to you after your chemotherapy is complete. You
will be asked to sign a separate consent for the chemotherapy.

You will receive the cells only if you respond to the chemotherapy (partial or complete
response). In case you are not able to receive the cells, they will remain frozen in the M.
D. Anderson laboratory permanently. You may be able to receive the cells at a later date if
the disease responds to additional chemotherapy treatment. You will have to discuss this
further with your treating leukemia doctor.

Study Tests:

About 4 weeks after finishing chemotherapy, you will have the following tests performed:

- You will have a complete physical exam.

- You may have either a chest x-ray or a chest CT scan, if your doctor thinks it is
needed. You will also have a bone marrow biopsy.

- Blood (about 3 tablespoons) will be drawn for routine tests and tests of your liver and
kidney function.

- Blood will also be drawn to check for the level of alemtuzumab in the blood. This test
will be done every 2 weeks until the study staff cannot measure any alemtuzumab in your
blood.

T-Cell Infusion:

Once the alemtuzumab clears from your system, you will be scheduled for the infusion of
T-cells. This will be done in the outpatient clinic. The T cells will be given through a
needle in the vein in an outpatient treatment area. The infusion will last about 10-30
minutes.

Before the infusion, you will receive acetaminophen (Tylenol) by mouth and diphenhydramine
hydrochloride (Benadryl) by mouth or vein about 30-60 minutes before the infusion. These
drugs will be used to help lower the risk of side-effects. If side effects occur during
treatment, the doses of the drugs may be adjusted (up or down) until the symptoms are gone.
Also, if you experience side effects during treatment, you must stay in the clinic to be
observed for 2 hours after the drug is given or until the symptoms have stopped completely
(whichever is later). While in the outpatient area, your blood pressure, heart rate,
breathing rate, temperature, and the level of oxygen in your blood will be checked every
15-30 minutes.

If you have a severe allergic reaction during the infusion of the autologous T Cells, the
infusion will be stopped right away and you will be given any needed care by the doctor and
staff.

Follow-Up Testing:

You will be asked to come back to the clinic 30, 90, and 365 days (1 year) after the T-cell
infusion. At each visit, the following tests will be performed:

You will have complete physical exam.

- Blood (about 3 tablespoons) will be drawn for routine blood tests.

- You will have a bone marrow biopsy.

- You may also have either a chest x-ray or a CT scan to check the status of the disease.

- Blood (2 tablespoons) will also be drawn to see how well your immune system is
recovering.

This is an investigational study. T-cell collection and infusion is not considered a
standard treatment for CLL, and is not an FDA approved treatment. Up to 20 patients will
take part in the study. Fifteen patients will be enrolled at M. D. Anderson and 5 patients
will be enrolled at the University of Pennsylvania.