FCR and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia (CLL)

During the study, you will have up to 6 "cycles" of treatment. A cycle is made up of
treatment with the study drugs for 3-4 days and then about 3-1/2 weeks (25 days) of no
treatment (about 4 weeks total). Treatment with the study drugs will be given for 4 days in
a row on the first cycle, and 3 days in a row on Cycles 2-6. On Day 1 of each cycle, you
will receive rituximab through a needle in a vein. On Cycle 1, since it is your first
exposure to rituximab, it must be given slowly, so it may take 6-8 hours to complete. On the
cycles after that, it can be given more rapidly, over 3-4 hours. Cyclophosphamide and
fludarabine will be given separately through a needle in a vein on Days 2-4 of Cycle 1 and
Days 1-3 of Cycles 2-6. Cyclophosphamide and fludarabine will each be given over 30 minutes.
Bevacizumab will be given through a needle in a vein over 90 minutes on Day 3 of Cycle 1. If
it is well tolerated, the next dose of Bevacizumab will be given over 60 minutes on Day 2 of
Cycle 2. If the Cycle 2 dose is well tolerated, the next doses of Bevacizumab will be given
over 30 minutes on Day 2 of Cycles 2-6. In addition to the study drugs, you may also be
given fluids by vein to help flush the kidneys, to help prevent possible kidney damage. You
may receive up to 6 cycles of treatment. Treatment will be given on an outpatient basis. The
injections for each daily treatment visit should take less than 6 hours.

Up to 66 patients will take part in the study. All will be enrolled at M.D. Anderson.

Inclusion Criteria:

- Diagnosis of B-cell CLL

- Relapsed, fludarabine-sensitive (duration of response > 6 months as assessed by prior
treating physician) or fludarabine-naive patients

- Rai Stage III or IV, or Rai Stage I or II if determined to have disease progression
as evidenced by rapid doubling of peripheral lymphocyte count, progressive
lymphadenopathy, progressive splenomegaly, or B symptoms.

- Prestudy WHO Performance Status
- Signed, written Institutional Review Board (IRB)approved informed consent.

- Men and women of reproductive potential must agree to follow accepted birth control
methods during treatment and for 3 months after completion of treatment.

- Acceptable liver function: Bilirubin (SGPT)
- Acceptable hematologic status: Platelet count >/= 50 x 10^9/L., absolute neutrophil
count (ANC) >/= 1 x 10^9/L.

- Acceptable renal function: Serum creatinine
Exclusion Criteria:

- Cancer radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or other
investigational therapy within 4 weeks prior to Study Day 1.

- Known infection with HIV, hepatitis B, or hepatitis C

- Transformation to aggressive B-cell malignancy (e.g., large B-cell lymphoma,
Richter's Syndrome, or prolymphocyte leukemia [PLL]).

- Patients with secondary malignancy requiring active treatment (except hormonal
therapy).

- Active uncontrolled bacterial, viral, or fungal infections.

- New York Heart Association Class II-IV cardiac disease or myocardial infarction
within the past 6 months prior to Study Day 1.

- Pregnant or currently breast-feeding.

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored
bevacizumab cancer study.

- Blood pressure of > 150/100 mmHg

- Unstable angina

- History of stroke within 6 months

- Clinically significant peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1, anticipation of need for major surgical procedure during the course
of the study.

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to Day 1.

- Urine protein:creatinine ratio >/= 1.0 at screening.

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 1.

- Serious, non-healing wound, ulcer, or bone fracture.