MCL is an uncommon and incurable clinicopathologic subtype of B-cell non-Hodgkin Lymphoma (NHL). Ibrutinib is a first-in-class potent, orally administered, covalently-binding small molecule inhibitor of Bruton's tyrosine kinase (BTKi) for the treatment of B-cell malignancies and chronic graft-versus-host disease. The primary hypothesis of the study is that ibrutinib plus rituximab using the recommended Phase 3 dosage selected in the Phase 2 part will prolong PFS versus physician's choice of lenalidomide plus rituximab or bortezomib plus rituximab, in participants with r/r MCL who are BTKi naive. The study will include a Screening Phase (up to 30 days prior to randomization), a Treatment Phase (from randomization until study treatment discontinuation), and a Post-treatment Follow-up Phase (from treatment discontinuation until death, consent withdrawal, or study end, whichever occurs first). Safety assessments include adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests, vital signs, electrocardiogram (ECG), physical examination. The total duration of the study will be up to 10 years 8 months.
The purpose of this study is to determine the recommended dosage of ibrutinib when administered in combination with rituximab in participants with relapsed or refractory (r/r) mantle cell lymphoma (MCL) (Phase 2); and to compare the progression-free survival (PFS) of ibrutinib plus rituximab versus physician's choice of lenalidomide plus rituximab or bortezomib plus rituximab (Phase 3).