Rituximab Plus Sargramostim (GM-CSF) In Patients With Chronic Lymphocytic Leukemia

GM-CSF is a drug designed to stimulate the immune system. It will increase the number of a
certain type of blood cell called neutrophils and macrophages.

Rituximab is a drug designed to bind to a protein, called cluster of differentiation antigen
20 (CD20), that is on the surface of the leukemia cells, allowing the leukemia cells to be
destroyed by the immune system.

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 medical history and physical exam, including routine blood
tests (about 2 tablespoons). A bone marrow aspirate will be collected. To collect a bone
marrow aspirate, 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amount of bone marrow is withdrawn through a large needle. Imaging studies (such as a chest
x-ray or CT scans) may be performed. Women who are able to have children must have a negative
blood pregnancy test.

If you are found to be eligible to take part in this study, you will receive GM-CSF as an
injection under the skin, three times a week for eight weeks. You will receive rituximab by
vein, once a week for four weeks. Usually, the first dose of rituximab requires several hours
to complete. Later doses should usually be shorter, but may vary according to individual
tolerance. Acetaminophen (Tylenol), diphenhydramine hydrochloride (Benadryl), and steroids
(hydrocortisone or similar) will be given before rituximab to decrease the risk of side
effects. If side effects do occur during the infusion, you will need to stay at the hospital
and be observed until the side effects have gone away. Other than that, treatment will be
given on an outpatient basis.

During treatment you will have routine blood tests (about 1 tablespoon) once a week. The
treatment will take about 8 weeks to be completed. You will be taken off study if your
disease gets worse or if the side effects become too severe.

After treatment is over, you will have a complete physical exam, including routine blood
tests (about 2 tablespoons). A bone marrow sample will be taken. Imaging studies (such as a
chest x-ray or CT scans) may be repeated to evaluate the effect of the treatment. If this
treatment has worked for you, your doctor may advise you to receive it again for a second
time.

You will then return for post-treatment evaluation every 6 months for 1 year and then once a
year for 3 years or until you start a new treatment.

This is an investigational study. GM-CSF and rituximab have been approved by the FDA for
clinical use. Their use together in this study, however, is experimental. Up to 130 patients
may take part in this study. All patients will be enrolled at M.D. Anderson Cancer Center.

Inclusion Criteria:

1. Group 1. Diagnosis of previously treated B-CLL Rai III-IV or earlier stage disease
with evidence of "active disease" as defined by the NCI-sponsored working group 1)
weight loss of >10% in prior 6 months, 2) extreme fatigue, 3) fever or night sweats
without evidence of infection, 4) worsening anemia or thrombocytopenia, 5) progressive
lymphocytosis with a rapid lymphocyte doubling time, 6) marked hypogammaglobulinemia
or paraproteinemia, 7) lymphadenopathy >5 cm in diameter.

2. Group 2. Diagnosis of previously untreated B-CLL with Rai stage 0-II disease but high
risk for progression based on B2-microglobulin >3.0 mg/mL, or with symptoms or
significant fatigue.

3. Group 3. Patients age 70 years of age and older with previously untreated B-CLL and
Rai stage III-IV or earlier stage disease with indication for treatment who refused
chemotherapy.

4. Age 15 years or above.

5. Adequate renal and hepatic functions (creatinine <2.5 mg/dL, bilirubin <2 mg/dL).
Patients with renal or liver dysfunction due to organ infiltration by lymphocytes are
eligible, as are patients with elevated bilirubin and history consistent with
Gilbert's disease.

6. Performance status <3 (Zubrod Scale).

7. No active viral hepatitis

Exclusion Criteria:

1) None.