Trial Information

A Phase II Study of Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) in Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)

Fludarabine is a chemotherapy drug that is approved for the treatment of CLL.
Cyclophosphamide is also a chemotherapy drug that is commonly used in the treatment of CLL.
Rituximab and alemtuzumab are special proteins that specifically target and attach to
proteins on leukemia cells. These targeted proteins may also be present on normal blood
cells. When these drugs bind to the proteins on leukemia cells, they may help to stop or
slow the growth of the disease. The combination of fludarabine, cyclophosphamide and
rituximab has been used in the treatment of CLL. The purpose of this study is to determine
if there is added benefit with the addition of alemtuzumab to this combination.

Before treatment starts, you will have a complete physical exam, including blood tests
(about 3 tablespoons). You may have either a chest x-ray or a computed tomography (CT) scan
if your doctor feel this is necessary. If you have not had a bone marrow sample collected
in the past 4 months, you will have a bone marrow sample collected at this time. To collect
a bone marrow sample, 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small amount of bone marrow is withdrawn through a large needle. Women who are able to have
children must have a negative blood pregnancy test.

During the study, you will have up to 6 "cycles" of treatment. A cycle is made up of
treatment with the study drugs for 5 days in a row, then around 31/2 weeks (23 days) of no
treatment with the study drugs. On Days 1, 3, and 5 of each cycle you will receive
alemtuzumab through a needle in a vein. On Day 2 of each cycle you will receive rituximab
through a needle in a vein. Cyclophosphamide and fludarabine will be given separately on
Days 3, 4, and 5 of each cycle through a needle in a vein. In addition to the study drugs,
you may also be given fluids by vein. The combination treatment will be repeated every 4
weeks (one cycle) for a total of up to 6 cycles. This treatment will be given on an
outpatient basis. The injections for each daily treatment visit should take less than 6
hours.

You will receive acetaminophen (Tylenol) by mouth and diphenhydramine hydrochloride
(Benadryl) by mouth or vein 30 - 60 minutes before each dose of rituximab and alemtuzumab.
You will also receive hydrocortisone (a steroid) by vein before each dose of alemtuzumab.
These drugs will be used to help decrease side effects. If side effects occur during a
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 for 2
hours after the drug is given to be observed.

If you begin to experience side effects due to treatment, the dose(s) of the drug(s) may be
lowered or the treatment may be temporarily stopped until the symptoms are gone.

During the treatment and for two months after completion of treatment you will need to take
prophylactic antibiotics to prevent you from developing infection.
Trimethoprim/sulfamethoxazole (Bactrim DS) is a sulfa-drug and you will be given this to
prevent a type of pneumonia called PCP pneumonia. If you are allergic to sulfa drugs, an
equivalent antibiotic will be given. You will take Valtrex to prevent virus reactivation
including herpes. If you are allergic to Valtrex, an equivalent antibiotic will be given.
You may receive an additional antibiotic to suppress another virus, cytomegalovirus called
Valcyte. You may also take allopurinol for the first week of the first course of treatment.
This will help prevent kidney damage from rapid destruction of your leukemia cells.

During the first cycle of treatment, you will have blood drawn (about 2 tablespoons) for
blood tests once a week. Then, these blood tests will be repeated before the start of each
additional cycle (every 4 weeks).

After 3 cycles of treatment, you will have a physical exam and blood tests (about 2
tablespoons). You may also have either an x-ray or a CT scan. You will have another bone
marrow sample collected. These tests will be used to see if the disease is responding to
treatment. If it is found that the disease is not responding to treatment after the first 3
cycles of therapy, you will be taken off the study and your doctor will discuss other
treatment options with you. If it is found that the disease is responding to treatment,
another 3 cycles (12 weeks) of treatment will be given (6 cycles total). During these
additional 3 cycles of therapy, you will have blood drawn (about 2 tablespoons) once a week
for routine blood tests.

After 6 cycles of treatment, you will have a physical exam and have around 2 tablespoons of
blood drawn for routine blood tests.

Around 3-6 months after you receive your last treatment cycle, you will have a physical exam
and blood tests (about 2 tablespoons). After that, you will have a physical examination and
blood tests (about 2 tablespoons) every 6 months for the next 2 years. If your disease
returns or if you start on more treatment, you will not need to return for these visits.
However, you should inform the study doctor/staff that you are receiving other treatment.

If at any time during the study the disease gets worse or you experience any intolerable
side effects, you will be taken off the study and your doctor will discuss other treatment
options with you.

This is an investigational study. All of the drugs used in the study are FDA approved and
commercially available. As many as 80 patients will take part in the study. All will be
enrolled at M. D. Anderson.