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

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.

Inclusion Criteria:

- 18 to 75 years of age

- Previously untreated with histologically confirmed grade 1, 2 or 3a CD20-positive
follicular lymphoma, with any of the GELF (Groupe d'Etude de Lymphomes Folliculaires)
treatment criteria prior to induction.

- Achieved a response to induction treatment with either R-CHOP (6 cycles of R-CHOP21
or R-CHOP14), R-CVP (6 cycles), or R-B (4 to 6 cycles).

- Must have completed all doses of the induction treatment, except for the
modifications allowed in the protocol.

Exclusion Criteria:

- Transformation to high grade lymphoma (secondary to "low grade" FL)

- Grade 3b follicular lymphoma

- Primary follicular lymphoma of the skin or gastrointestinal tract

- Previous treatment of follicular lymphoma

- Altered renal and hepatic function

- Known HIV infection and/or active HBV and/or HCV infection

- Serious co-morbid conditions (for example, ongoing infection, uncontrolled diabetes
mellitus, gastric ulcers, active autoimmune disease).

- Life expectancy < 6

- Must have:

- Platelet count ≥ 100x109/L

- Bone marrow infiltration <25%