Rituximab or Zevalin - Efficacy Trial of Therapeutic Alternatives (RoZetta)

• Progression-free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  Progression-free survival (PFS), defined as time from randomization to progression, relapse and/or death from any cause, or need for a new treatment regardless of reason.
  
  

• Complete Response Rate [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
  Complete Response (CR) rates post randomization
  
  
• Event Free Survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  EFS time is defined as the time from randomization to first documented progression, death from any cause, or introduction of a new anti-lymphoma treatment (chemotherapy, radiotherapy or immunotherapy).
  
  
• Time to Progression (TTP) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  TTP is defined as the time from randomization to the first disease progression.
  
  
• Time to Next Anti-Lymphoma Treatment (TTNLT) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  TTNLT is defined as the time from randomization to the first introduction of any new anti lymphoma regimen.
  
  
• Time to Next Chemotherapy (TTNCT) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  TTNCT is defined as the time from randomization to the first introduction of any new chemotherapy (cytotoxic or radioimmunotherapy). The TTNCT may be the same as the TTNLT. Patients who respond to treatment and patients who are lost to follow-up will be censored at the visit on which the dosing of a new medication was evaluated.
  
  
• Overall Survival (OS) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  OS is defined as the time from randomization to death from any cause. In living patients, survival time will be censored on the last date patients were known to be alive.
  
  
• Overall Response Rate (ORR) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  Tumor response will be evaluated according to Cheson criteria at the time of randomization and at the end of the 2-year maintenance/observation, post randomization. ORR is defined as the proportion of patients with a CR or a PR, and will be compared between treatment groups. Patients with no response evaluation (for any reason) will be considered as not evaluable (NE).
  
  
• Transformation at First Progression [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  Transformation rate at first progression, defined as the appearance of diffuse areas of large lymphoma cells within a tumor site.
  
  
• Quality of Life (QoL) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  QoL will be assessed through EORTC FACT-G and QLQ-[C]30 questionnaires, and will be compared at each specified time point between treatment arms.
  
  
• Pharmacoeconomics (cost effectiveness analysis) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
  A cost-effectiveness analysis will be done that compares the efficiency (cost/effectiveness unit) of consolidation treatment with 90Y-ibritumomab tiuxetan compared to maintenance treatment with rituximab. The analysis will be conducted according to a health economic analysis plan independent from this clinical study protocol.
  
  

This is an open-label, multicenter and randomized study. Patients will be registered after response induction (PR/CR) to R-chemotherapy. Patients achieving either a PR or CR following R-chemotherapy will be eligible for randomization to either consolidation with 90Y-ibritumumab tiuxetan followed by observation for 24 months, or rituximab maintenance for 24 months. After the observation/maintenance period, patients will be followed for 5 years.

This study is designed to be similar to the ZAR2007 study (EUDRACT No. 2007-006601-25) carried out by PETHEMA in Spain. It is expected that Spanish centers will contribute up to 230 patients; centers in the US and elsewhere will contribute the remaining 254 patients. The same randomization procedure will be used in both studies. The total sample size for the combined studies will be 484 randomized patients. Assuming that PFS will follow an exponential distribution with a constant hazard rate, with a 36 months uniform accrual period and an additional follow-up time of 60 months after the last patient is randomized, 242 patients per arm (484 total) will be necessary to observe 131 PFS events in the combined study.