Identifying Prognostic Factors in Frontline FCR for Patients With Chronic Lymphocytic Leukemia (CLL)

The Study Drugs:

Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic
material of cells). This may increase the likelihood of the cells dying.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may
slow or stop their growth and spread throughout the body. This may cause the cancer cells to
die.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

Study Drug Administration:

Each cycle is 4-6 weeks.

If you are found to be eligible to take part in this study, on Day 1 of each cycle, you will
receive rituximab through a needle into your vein over 6-8 hours.

On Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond, you will receive fludarabine by
vein over 30 minutes. You will also receive cyclophosphamide by vein over 30 minutes.

You will receive drugs (such as Tylenol, Benadryl, Zofran, allopurinol, and Valtrex) to help
prevent side effects. If you have side effects while receiving rituximab, you may be
monitored by the study staff for 2 hours after each dose.

Study Visits:

Once a week, blood (about 1 tablespoon) will be drawn for routine tests.

After 3 months (3 cycles of treatment), the following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- You will have a bone marrow aspirate and biopsy to check the status of the disease.

Length of Study:

You will be on treatment for about 6 months. You will be taken off treatment early if you
have intolerable side effects or the disease gets worse.

End-of-Treatment Visit:

After you are off treatment, you will have an end-of-treatment visit for doctors to learn
your overall response to the treatment. The following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- You will have a bone marrow aspirate and biopsy to check the status of the disease.

Long-Term Follow-up:

At 6 months after you have finished treatment and then every year from then on, you will have
follow-up visits. The following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- If your doctor thinks it is needed, you will have a bone marrow biopsy and aspirate to
check the status of the disease.

This is an investigational study. Fludarabine, cyclophosphamide, and rituximab are FDA
approved and commercially available for the treatment of CLL. The correlation with response
to treatment and the characteristics of the leukemia cells is investigational.

Up to 300 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients will have a diagnosis of CLL, SLL, or CD20 positive low-grade
lymphoproliferative disorder.

2. All patients with untreated Rai stage III-IV are eligible for this protocol. Prior
treatment with single-agent rituximab permitted. OR Patients with untreated Rai stage
0-II who meet one or more criteria for active disease as defined by the International
Working Group for CLL (IWCLL). Prior treatment with single-agent rituximab permitted.

3. Patients must have an ECOG performance status of 0-3.

4. Patients must have adequate renal and hepatic function (creatinine <2mg%, bilirubin
<2mg%). Patients with renal or liver dysfunction due to organ infiltration by
lymphocytes may be eligible after discussion with the study chairman.

5. Patients may not receive other concurrent chemotherapy, radiotherapy, or
immunotherapy. Localized radiotherapy to an area not compromising bone marrow function
does not apply.

6. Patients must be 16 years of age or older.

7. Patients must sign informed consent indicating that they are aware of the
investigational nature of this study according to the policies of the MDACC IRB.

Exclusion Criteria: