A Study of PCI-32765 (Ibrutinib) in Patients With Refractory Follicular Lymphoma

Inclusion Criteria:

• Histologic proof of Grade 1, 2, or 3a follicular lymphoma (FL) without clinical or pathological evidence of transformation
• Previously treated with at least 2 prior lines of therapy, including at least 1 rituximab combination chemotherapy regimen; last prior line of therapy includes an anti CD20 monoclonal antibody-containing chemotherapy regimen (separate lines of therapy are defined as different regimens that are either separated by disease progression, refractory disease, or relapsed disease)
• Resistant disease to the last therapy, defined as progression of disease during or within 12 months of the last dose of chemotherapy in a CD20 antibody combination chemotherapy regimen
• At least 1 measurable site of disease according to International Working Group Revised Response Criteria for Malignant Lymphoma
• Eastern Cooperative Oncology Group performance status grade 0 or 1
• Hematology and biochemical laboratory values must be within protocol-defined parameters within 7 days prior to enrollment
• Agrees to protocol-defined use of effective contraception
• Women of childbearing potential must have a negative serum or urine pregnancy test at screening

Exclusion Criteria:

• Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of first dose of study drug
• Prior treatment with PCI-32765 or other Bruton's tyrosine kinase inhibitors (patients who progressed or became refractory while on treatment with PI3K inhibitors are excluded)
• Concurrent enrollment in another therapeutic investigational clinical treatment study
• Received a prior allogeneic hematopoietic stem cell transplant (prior autologous hematopoietic stem cell transplant is allowed)
• Known central nervous system lymphoma
• History of prior malignancy (except malignancy treated with curative intent and with no known active disease present for >=3 years before enrollment, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, or adequately treated cervical carcinoma in situ without evidence of disease)
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists
• Requires treatment with strong cytochrome P450 (CYP)3A4/5 inhibitors
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C or active infection with Hepatitis B or any uncontrolled active systemic infection requiring intravenous antibiotics
• Women who are pregnant or breastfeeding
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue risk