A Study of PCI-32765 (Ibrutinib) in Combination With Either Bendamustine and Rituximab or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Participants With Previously Treated Indolent Non-Hodgkin Lymphoma

This is a randomized (individuals assigned to study treatment by chance), double-blind
(individuals and study personnel will not know the identity of study treatments), placebo (an
inactive substance that is compared with a drug to test whether the drug has a real effect in
a clinical trial)-controlled study in approximately 400 adult participants with follicular
lymphoma or marginal zone lymphoma. The study will include the following phases: Screening,
Treatment, and a Post-treatment Follow-up. Eligible participants will be randomly assigned in
a 1:1 ratio to either treatment Arm A (background immune-chemotherapy + placebo) or treatment
Arm B (background immune-chemotherapy + 560 milligram [mg] of ibrutinib). All participants
will receive 6 cycles of background immune-chemotherapy with either BR or R-CHOP in
combination with either placebo (Arm A) or ibrutinib (Arm B). Selection of background
immune-chemotherapy will be based on prior treatment history and cardiac function. After
completion of background immune-chemotherapy, study drug (ibrutinib or placebo) will continue
until disease progression, unacceptable toxicity, or study end, whichever comes first.
Assessment of tumor response and progression will be conducted in accordance with the Revised
Response Criteria for Malignant Lymphoma. Serial pharmacokinetic (study of what a drug does
to the body) blood samples will be collected. Safety will be assessed throughout the study.

Inclusion Criteria:

- Histologically confirmed diagnosis of B-cell indolent Non-Hodgkin lymphoma with
histological subtype limited to follicular lymphoma or marginal zone lymphoma, at
initial diagnosis and without evidence of pathological transformation or clinical
signs suggesting transformation

- At least 1 prior treatment with a CD20 antibody combination chemo-immunotherapy
regimen

- Disease that has relapsed or was refractory after prior chemo-immunotherapy

- At least 1 measurable site of disease according to Revised Response Criteria for
Malignant Lymphoma 2007

- Eastern Cooperative Oncology Group performance status grade 0 or 1

- Laboratory values within protocol-defined parameters

- Agrees to protocol-defined use of effective contraception

- Men must agree not to donate sperm during and after the study for 6 months after the
last dose of bendamustine, 12 months after the last dose of rituximab, or 3 months
after the last dose of study medication, whichever is later

- Women of childbearing potential must have a negative serum or urine pregnancy test at
Screening

Exclusion Criteria:

- Prior treatment according to protocol-defined criteria

- Unable to receive background chemotherapy based on prior treatment history and cardiac
function

- Known central nervous system lymphoma

- Diagnosed or treated for malignancy other than indolent Non-Hodgkin lymphoma

- History of stroke or intracranial hemorrhage within 6 months prior to randomization

- Requires anticoagulation with warfarin or equivalent Vitamin K antagonists

- Requires treatment with strong CYP3A inhibitors

- Clinically significant cardiovascular disease

- Known history of human immunodeficiency virus or active hepatitis C virus (HCV;
ribonucleic acid [RNA] polymerase chain reaction [PCR]-positive) or active hepatitis B
virus (HBV; DNA PCR-positive) infection or any uncontrolled active systemic infection
requiring intravenous antibiotics

- Any life-threatening illness, medical condition, or organ system dysfunction which, in
the Investigator's opinion, could compromise the participant's safety, interfere with
the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue
risk

- Women who are pregnant or breastfeeding