Inclusion Criteria

-INCLUSION CRITERIA:

1. Cohort 1: Treated and untreated patients age 65 or older and need for therapy

Cohort 2: Treated (maximum accrual n=16) and untreated (n=27, evaluable) patients at
least 18 years old with 17p deletion or p53 expression by immunohistochemistry or p53
mutation by sequencing analysis.

2. Men and women with histologically confirmed disease as defined by the following:

- B-lymphocytosis greater than 5000 cells/microL (may be less than 5000
cells/microL if lymphadenopathy is present with histologic confirmation of lymph
node involvement by SLL)

- Immunophenotypic profile read by an expert pathologist as consistent with CLL.
This will include CD5, CD19, and CD20 expression by the CLL cells typically
also with CD23 expression, but CD23 negative cases may be included if there is
no t11;14 translocation present.

3. Active disease as defined by at least one of the following:

- Weight loss greater than or equal to 10% within the previous 6 months

- Extreme fatigue

- Fevers of greater than 100.5 degrees F for greater than or equal to 2 weeks
without evidence of infection

- Night sweats for more than one month without evidence of infection

- Evidence of progressive marrow failure as manifested by the development of, or
worsening of, anemia and/or thrombocytopenia

- Massive or progressive splenomegaly

- Massive nodes or clusters or progressive lymphadenopathy

- Progressive lymphocytosis with an increase of greater than 50% over a 2 month
period, or an anticipated doubling time of less than 6 months

- Compensated autoimmune hemolysis

4. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
2

5. ANC greater than 500/microL, platelets greater than 30,000/microL

6. Agreement to use contraception during the study and for 30 days after the last dose
of study drug if sexually active and able to bear children

7. Willing and able to participate in all required evaluations and procedures in this
study protocol including swallowing capsules without difficulty

8. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (in accordance
with national and local subject privacy regulations)

EXCLUSION CRITERIA:

1. Previous radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or
treatment with an investigational product in the last 4 weeks.

2. Transformed CLL

3. Autoimmune hemolytic anemia or thrombocytopenia requiring steroid therapy

4. Impaired hepatic function: Total bilirubin greater than or equal to 1.5 times upper
limit of normal unless dute to Gilbert's disease, AST/ ALT greater than or equal to
2.5 times institutional upper limit of normal unless due to infiltration of the
liver.

5. Impaired renal funtion: Creatinine greater than or equal to 2.0 mg/dL or GFR less
than or equal to 50ml/min

6. Life-threatening illness, medical condition or organ system dysfunction which, in the
investigator's opinion, could compromise the subject's safety, interfere with the
absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk

7. Concomitant immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages
equivalent to prednisone > 20 mg/day), or experimental therapy

8. Active Hepatitis B infection

9. HIV infection

10. Female patients: Current pregnancy or unwilling to take oral contraceptives or
refrain from pregnancy if of childbearing potential or currently breastfeeding. Male
patients who are unwilling to follow the contraception requirements described in this
protocol.

11. Psychiatric illness/social situations that would limit the patient's ability to
tolerate and/or comply with study requirements.

12. Unable to understand the investigational nature of the study or give informed
consent.

13. Individuals < 18 yrs old

14. Known hypersensitivity to any component of PCI-32765

15. Any prior therapy with PCI 32765 or any other BTK inhibitors.

16. Requires anticoagulation with warfarin.

17. Requires treatment with strong CY3A4/5 and/or CYP2D6 inhibitors (unless no
alternative is available).