A Study of PCI-32765 (Ibrutinib) Versus Rituximab in Relapsed or Refractory Chronic Leukemia/Lymphoma

A Randomized, Multicenter, Open-Label, Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor PCI-32765 (Ibrutinib) Versus Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

The purpose of this study is to evaluate the efficacy and safety of ibrutinib versus rituximab in adult Asia Pacific region patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known) study designed to evaluate the efficacy and safety of ibrutinib versus rituximab in adult Asia Pacific region patients with relapsed/refractory CLL or SLL with active disease requiring treatment who have failed at least 1 prior line of therapy and are not considered appropriate candidates for treatment or retreatment with purine analog-based therapy. Approximately 150 patients will be randomly assigned in a 1:2 ratio into 2 treatment arms to receive either intravenous rituximab (Treatment Arm A) for 6 cycles or oral ibrutinib (Treatment Arm B) until disease progression or unacceptable toxicity, whichever occurs first. The study will include screening, treatment, and follow-up phases. Treatment will extend from randomization until study drug discontinuation. Follow-up will consist of 2 phases: post-treatment (from the discontinuation of treatment for reasons other than disease progression until the patient has progressive disease) and post-disease progression (subsequent anticancer therapy and survival status will be recorded until death, lost to follow-up, consent withdrawal, or study closure). Patients in the rituximab arm with disease progression or who meet the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for requiring subsequent anti-CLL therapy may be considered for cross over to receive ibrutinib 420 mg orally, daily until disease progression, unacceptable toxicity, withdrawal from study, or until study end whichever occurs earliest. Efficacy evaluations will assess for disease response and progression in accordance with International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. Serial pharmacokinetic (study of what a drug does to the body) blood samples will be collected in the ibrutinib treatment group. Safety will be assessed throughout the study.

Inclusion Criteria:

• Eastern Cooperative Oncology Group performance status of 0-1
• Diagnosis of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
• Laboratory values within protocol-defined parameters
• Active disease meeting International Workshop on Chronic Lymphocytic Leukemia 2008 criteria
• Received at least 1 prior therapy for CLL/SLL and not appropriate for treatment or retreatment with purine analog-based therapy
• Measurable nodal disease by computed tomography
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test at Screening and agree to use highly effective methods of contraception during the study and for 90 days following the last dose with ibrutinib or 12 months following the last dose of rituximab

Exclusion Criteria:

• Central nervous system lymphoma or leukemia
• Prolymphocytic leukemia or history of or currently suspected Richter's transformation
• Refractory to prior rituximab-based therapy
• Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days prior to first dose of study drug
• Corticosteroid use >20 mg within 1 week prior to first dose of study drug
• Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose of study drug
• Prior autologous transplant within 6 months prior to first dose of study drug
• Prior allogeneic stem cell transplant
• Major surgery within 4 weeks prior to first dose of study drug
• History of prior malignancy according to protocol-defined criteria
• Currently active clinically significant cardiovascular disease within 6 months prior to first dose with study drug
• Uncontrolled active systemic fungal, bacterial, viral, or other ongoing anti-infective treatment administered intravenously
• History of human immunodeficiency virus or active infection with hepatitis B or C
• History of stroke or intracranial hemorrhage within 6 months prior to random assignment
• Pregnant or lactating women
• Current life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, or put the study at risk
• Requires or receiving anticoagulation with warfarin or equivalent Vitamin K antagonists
• Requires treatment with a strong CYP3A4/5 inhibitor
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (greater than [>]20 milligram [mg] daily of prednisone daily or equivalent)