Fludarabine, Cyclophosphamide, and Rituximab - High Dose Frontline

DESCRIPTION OF RESEARCH

Fludarabine and cyclophosphamide are chemotherapy drugs that are used in the treatment of
CLL. Rituximab is a monoclonal antibody that binds to lymphoma cells and causes cell death.

Before treatment starts, you will have a complete physical exam and routine blood tests
(about 2 teaspoons). A bone marrow sample will be collected. To collect a bone marrow sample,
an area of the hip or chest bone is numbed with anesthetic 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is withdrawn through a large needle.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 or urine pregnancy test.

Rituximab will be given through a needle (IV) in a vein on Days 1, 2, and 3. One day after
the first dose of rituximab (Day 2), fludarabine and cyclophosphamide will be given through a
needle (IV) in a vein daily for 3 days (Days 2, 3, 4). After the first month, all the drugs
will be given on Days 1, 2, 3. Other IV fluids such as saline will be given on all of the
treatment days for hydration, which means that the daily visit will take about six hours. The
combination will be repeated once every 4 to 6 weeks for a total of 6 courses.

The drugs acetaminophen (Tylenol) and diphenhydramine hydrochloride (Benadryl) will be given
before the dose of rituximab. This will be done to decrease the risk of side effects. If side
effects do occur during rituximab treatment, the drug may have to be stopped until the side
effects go away and then restarted so the time in the outpatient area may be longer.

The first treatment will be given at M. D. Anderson. The other 5 courses can be performed
ether at M. D. Anderson or at home with your regular physician.

The same doses of all three drugs will be used throughout the study unless side effects
become severe. In that case, the dose may be lowered or the treatment may be stopped. You
will be taken off study if the disease gets worse.

During treatments, patients will have blood samples (about 1 teaspoon each) taken once every
1-2 weeks. Bone marrow studies will be done at the end of the 3rd and 6th chemotherapy
courses.

After treatment is completed, you will have blood tests (about 2 teaspoons each) done every 3
months for as long as you are in remission.

This is an investigational study. The FDA has approved all of the drugs used in this study
and they are commercially available. However, their use in this study is investigational. As
many as 64 patients will take part in the study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. 16 years or older

2. Untreated CLL with indication for therapy or minimally treated (e.g. less than 1 month
of steroids or chemotherapy) are eligible

3. Performance status of 3 or better (Appendix A)

4. Adequate renal and hepatic function (creatinine <2 mg%, bilirubin <2mg%). Patient with
renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible
after discussion with the study chairman but upper limits for creatinine even under
these circumstances would be creatinine < 3 mg% and bilirubin < 6 mg%. Patients with
Gilbert's Syndrome may be entered on study with bilirubin 2-7 mg%..

5. A signed informed consent in keeping with policies of the hospital

Exclusion Criteria:

1) None