Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

• Progression free survival [ Time Frame: clinical cutoff (defined by 178 patients with progression free survival events; up to 3 years after the last patient is randomized) ] [ Designated as safety issue: No ]
  

• Overall response rate [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  
• Overall survival [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  
• 1-year survival rate [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  
• Duration of response [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  
• Time-to-next treatment [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  
• Number of participants with adverse events [ Time Frame: up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  
• Mean plasma concentrations of ibrutinib [ Time Frame: Cycles 1-2: predose on Day 1, postdose at 1, 2, and 4 hours; and Cycle 3: predose on Day 1 ] [ Designated as safety issue: No ]
  
• Maximum observed plasma concentration of ibrutinib [ Time Frame: Cycles 1-2: predose on Day 1, postdose at 1, 2, and 4 hours; and Cycle 3: predose on Day 1 ] [ Designated as safety issue: No ]
  
• Minimum observed plasma concentration of ibrutinib [ Time Frame: Cycles 1-2: predose on Day 1, postdose at 1, 2, and 4 hours; and Cycle 3: predose on Day 1 ] [ Designated as safety issue: No ]
  
• Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib [ Time Frame: Cycles 1-2: predose on Day 1, postdose at 1, 2, and 4 hours; and Cycle 3: predose on Day 1 ] [ Designated as safety issue: No ]
  
• Mean change from baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale score [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  
• Mean change from baseline in EuroQol (EQ-5D-5L) index score [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  
• Mean change from baseline in medical resource utilization [ Time Frame: up to 30 days from last dose of study medication ] [ Designated as safety issue: No ]
  
• Mean change from baseline in biomarkers that alter B-cell receptor (BCR) signaling or activate alternative signaling pathways [ Time Frame: up to 30 days from last dose of study medication ] [ Designated as safety issue: No ]
  
• Mean change from baseline in identified resistance biomarkers from bone marrow [ Time Frame: up to 30 days from last dose of study medication ] [ Designated as safety issue: No ]
  

This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known), study to evaluate the efficacy and safety of ibrutinib when compared with temsirolimus in patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 1 prior rituximab-containing chemotherapy regimen. Approximately 280 eligible patients will be randomly assigned in a 1:1 ratio and stratified (grouped) by the number of prior lines of therapy (1 or 2 versus >=3) and simplified MCL International Prognostic Index criteria to receive either ibrutinib by mouth (Treatment Arm A) or temsirolimus intravenous infusion (Treatment Arm B). The study will consist of screening, treatment, and posttreatment phases. Data will be collected on disease response to the treatment, progression-free survival, overall survival, subsequent anti-MCL therapies, patient reported outcomes, and medical resource utilization. Tumor samples, blood collected at multiple time points, and a bone marrow aspirate will be evaluated to identify markers predictive of response or resistance to ibrutinib. Serial pharmacokinetic (study of what the body does to a drug) samples will be collected as detailed in the protocol. Safety will be monitored throughout the study. Disease evaluations will be performed every 9 weeks for up to 15 months from the start of study drug, and every 24 weeks thereafter, until disease progression, death, or the clinical cutoff, whichever comes first. Data will be analyzed up to 3 years after the last patient is enrolled for the final follow-up.