FCM-R (Fludarabine, Cyclophosphamide, Mitoxantrone, Rituximab) in Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL) < 70 Years

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.

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 University of Texas MD Anderson Cancer Center
(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 MD Anderson.

Inclusion Criteria:

1. Untreated CLL, CLL/ prolymphocytic leukemia (PLL), or small lymphocytic lymphoma (SLL)
with indication for therapy (Indications for therapy include at least one of the
following: i) one or more disease-related symptoms [fever, night sweats, weight loss,
pronounced fatigue]; ii) advanced stage disease (Rai stage >/= 3 or Binet stage C);
iii) autoimmune anemia and/or thrombocytopenia that is unresponsive to other
therapies; iv) massive or progressive hepatomegaly and/or splenomegaly and/or
lymphadenopathy; iv) recurrent infections; v) rapid lymphocyte doubling time of < 6
months).

2. Age < 70 years.

3. Adequate liver function (total bilirubin transaminase (SGPT) Patients with renal or liver dysfunction due to suspected organ infiltration by
lymphocytes may be eligible after discussion with the Principal Investigator, but
upper limits for creatinine even under these circumstances must be creatinine < 3mg/dL
and bilirubin < 6 mg/dL. Patients with Gilbert's syndrome may be entered on study with
bilirubin levels
4. Beta-2-microglobulin
5. Eastern Cooperative Oncology Group (ECOG) performance status
6. Signed informed consent in keeping with the policies of the hospital.

7. Male and female patients who are fertile agree to use an effective barrier method of
birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
Female patients of childbearing potential (non-childbearing is defined as >/= 1 year
postmenopausal or surgically sterilized) need a negative serum or urine pregnancy test
within 14 days of study enrollment.

Exclusion Criteria:

1. Active hepatitis B (at least one of the following markers positive: HBsAg, HBeAg,
Immunoglobulin M (IgM) hepatitis B core antibody (anti-HBc), Hepatitis B (HBV) DNA).

2. Concurrent chemotherapy or immunotherapy.

3. Pregnant patients.

4. History of HIV

5. Symptomatic central nervous system (CNS) disease

6. Symptomatic heart disease (NYHA class >/= 3) or left ventricle (LV) ejection fraction
< 40% (by multiple gated acquisition scan (MUGA) or echocardiogram)