Trial Information

Phase 2 Study of the Activity and Safety of Fludarabine, Cyclophosphamide, and Mitoxantrone Plus Rituximab (FCM-R) With Pegfilgrastim (Neulasta) as Frontline Therapy for Patients < 70 Years With Chronic Lymphocytic Leukemia

Fludarabine, cyclophosphamide, and mitoxantrone are chemotherapy drugs that are used in the
treatment of CLL. Rituximab is a monoclonal antibody that binds to CLL cells and causes
cell death. Pegfilgrastim (Neulasta) is a growth factor that helps the bone marrow to
produce white cells (neutrophils) and is an approved drug to treat the suppression of marrow
function caused by chemotherapy.

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 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or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn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 before treatment begins. A heart test ("MUGA scan" or "echocardiogram")
is required within at least 3 months before treatment start. This can be done here at MD
Anderson or by your own doctor at home.

If you are eligible to take part in the study, you will begin treatment. Rituximab will
be given through a needle in your vein (IV) on Day 1 of Courses 1-6. 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
acetaminophen (Tylenol) and diphenhydramine hydrochloride (Benadryl) 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.

One day after the first dose of rituximab (Day 2), fludarabine and cyclophosphamide will be
given by IV every day for 3 days (Days 2, 3, and 4), and mitoxantrone will be given by IV on
Day 2. Fludarabine and cyclophosphamide will be given as 30-minute infusions, while the
infusion of mitoxantrone will take 30-60 minutes. After the first treatment cycle, all the
drugs will be given on Days 1, 2, and 3 for every cycle after that. Pegfilgrastim will be
given as a subcutaneous injection (an injection under the skin) once per treatment cycle,
right after you receive the last chemotherapy drug (in other words, on Day 4 during the
first cycle, and on Day 3 for every cycle after that). Other IV fluids, such as saline,
will be given on all of the treatment days to keep you hydrated, which means that each
clinic visit will take about 6 hours. The combination will be repeated once every 4 to 6
weeks for a total of 6 courses.

The first treatment will be given at the UTMDACC outpatient clinic. The other 5 courses can
be performed either at UTMDACC or at home with your regular physician.

During each treatment cycle, you will have blood samples (about 1 teaspoon each) drawn once
every 1-2 weeks. Bone marrow biopsies will be performed at the end of Cycles 3 and 6 of
chemotherapy.

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. You will be taken off study if the disease gets worse.

After Course 6 of chemotherapy is finished, you will have blood tests (about 2 teaspoons
each) performed every 6-12 months.

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 and in this
combination is considered investigational. Up to 30 patients will take part in the study.
All will be enrolled at UTMDACC.