A Phase 1b/2 Fixed-dose Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Chronic Lymphocytic Leukemia

Inclusion Criteria:

1. FOR TREATMENT-NAIVE GROUP ONLY: Men and women ≥ 65 years of age with confirmed
diagnosis of CLL/SLL, who require treatment per NCI or International Working Group
guidelines 15-18

2. FOR RELAPSED/REFRACTORY GROUP ONLY: Men and women ≥ 18 years of age with a confirmed
diagnosis of relapsed/refractory CLL/SLL following previous therapy(ie, failed ≥ 2
previous treatments for CLL/SLL and at least 1 regimen had to have had a purine
analog [eg, fludarabine] for subjects with CLL)

3. FOR HIGH-RISK RELAPSED/ REFRACTORYGROUP ONLY: Men and women ≥ 18 years of age with a
confirmed diagnosis of relapsed/refractory CLL/SLL with suboptimal response to
chemoimmunotherapy, defined as progression of disease within 24 months of initiation
of a regimen containing at least a nucleoside analogue or bendamustine in combination
with a monoclonal antibody or failure to respond to such a regimen. (Note: a minimum
of 2 cycles of chemoimmunotherapy required for eligibility)

4. ECOG performance status of ≤ 2

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

Exclusion Criteria:

1. Prior malignancy, except for adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, or other cancer from which the subject has been
disease free for at least 2 years or which will not limit survival to < 2 years

2. Any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks
before first dose of study drug (corticosteroids for disease-related symptoms allowed
but require 1-week washout before study drug administration)

3. Central nervous system (CNS) involvement by lymphoma

4. Major surgery within 4 weeks before first dose of study drug

5. Concomitant use of medicines known to cause QT prolongation or torsades de pointes

6. Significant screening electrocardiogram (ECG) abnormalities including left bundle
branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc >
470 msec

7. Lactating or pregnant