Trial Information

Fludarabine, Cyclophosphamide, and Rituximab (FCR) Plus Sargramostim (GM-CSF) as Frontline Therapy for Symptomatic Chronic Lymphocytic Leukemia

Fludarabine and cyclophosphamide are designed to enter CLL cells and destroy the "machinery"
that allows CLL cells to multiply. Rituximab is designed to bind to CLL cells and cause
cell death. GM-CSF is designed to help the bone marrow to produce white cells. It may also
increase the target molecule (called "CD20") for rituximab on the surface of the CLL cells
which may improve the activity of rituximab.

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. Blood (about 2 tablespoons) will be drawn
for routine tests. The routine blood draw will include a test for hepatitis B, unless this
has been done within the last 6 months. This routine blood draw will also include a
pregnancy test for women who are able to have children. To be eligible to take part in this
study, the pregnancy test must be negative. A bone marrow aspirate and biopsy will be
collected. To collect a bone marrow aspirate and biopsy, an area of the hip or chest bone is
numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a
large needle.

If you are found to be eligible to take part in the study, you will receive GM-CSF thorough
a needle under your skin on Day 1. Each study cycle is about 4 weeks, but may be longer
depending on side effects or leukemia response.

You will receive rituximab through a needle in your vein on Day 2. The first infusion may
take up to 8 hours. For every dose of rituximab after that, the infusion may take 2-4
hours. The length of the infusion time depends on whether you have any reactions to the
infusion. The dose level of rituximab may be increased for Cycles 2-6 as well. The drugs
Tylenol (acetaminophen) and Benadryl (diphenhydramine hydrochloride) will be given before
each 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 your time in the outpatient area may be longer if
that occurs.

On Days 3-5 of the first treatment cycle, fludarabine and cyclophosphamide will be given
through a needle in your vein. Each infusion will take about 30 minutes. After the first
treatment cycle, fludarabine and cyclophosphamide will be given on Days 2, 3, and 4 for
every cycle after that.

During each cycle, the day after you receive fludarabine and cyclophosphamide, you will
begin to receive GM-CSF. You will receive the drug for 1 week or until your white cell
count has returned to an acceptable level.

Cycle 1 will be given at M.D. Anderson's outpatient clinic. In some cases, Cycle 1 may be
given in the inpatient area. The other 5 cycles can be given either at M.D. Anderson or at
another location.

With the exception of rituximab, the same doses of all other 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.

During each cycle, blood (about 1 tablespoon) will be drawn once every 1-2 weeks for routine
tests.

You will have a bone marrow biopsy performed at the end of Cycles 3 and 6 to check the
status of the disease.

You may remain on study for up to 6 cycles. You will be taken off study if the disease gets
worse or if intolerable side effects occur.

Once you are off study, blood (about 2 teaspoons) will be drawn every 6-12 months for
routine tests.

This is an investigational study. Fludarabine, cyclophosphamide, rituximab, and GM-CSF are
all FDA approved and commercially available. However, their use in this study and in this
combination is considered investigational. Up to 60 patients will take part in the study.
All will be enrolled at M.D. Anderson.