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

This is an open-label (identity of assigned study drug will be known) study of PCI-32765 (ibrutinib) in approximately 110 patients with chemoimmunotherapy-resistant FL whose disease has relapsed from at least 2 prior lines of therapy, including at least 1 rituximab combination chemotherapy regimen. Each patient must have resistant disease to the last therapy (defined as progression of disease \[PD\] during or within 12 months of the last dose of chemotherapy in a CD20 antibody combination chemotherapy regimen). The study will include the following phases: screening (up to 30 days prior to the first dose of study drug), treatment (until PD or unacceptable toxicity), and posttreatment follow-up (until death, lost to follow up, withdrawal of consent, or study end \[defined as 2 years after the last patient is enrolled\]). Patients will receive 560 mg of PCI-32765 by mouth once daily on a 21-day cycle. Treatment will be continuous (without interruption) and self-administered at home. The treatment phase will extend from administration of the first dose of study medication until PD or unacceptable toxicity. If a patient who had radiological evidence of PD is clinically stable or improving or exhibiting signs of tumor flare without confirmation of PD by PET or biopsy, they may continue treatment with ibrutinib upon request by the investigator and approval by the sponsor. Posttreatment follow-up will extend from the end of treatment until death, lost to follow up, withdrawal of consent, or study end. Every patient, except for those who explicitly withdraw consent from further site contact, will be followed for survival status until the study ends. In addition, data on subsequent antineoplastic therapy will also be collected. Serial pharmacokinetic samples will be collected and efficacy and safety will be monitored throughout the study. A separate assessment of pharmacokinetics is planned for patients who receive a strong or moderate CYP3A4/5 inhibitor while receiving treatment with ibrutinib. For patients who have already discontinued ibrutinib due to PD, have taken no other anticancer therapy, and now have a radiologically documented delayed response, resumption of ibrutinib is permitted on a case-by-case basis, upon request by the investigator and approval of the sponsor.