Phase 3 Study of Zevalin Following R-CVP in Previously Untreated Patients With Follicular Non Hodgkin's Lymphoma (NHL)

A Phase 3 Open Label Multicenter, Randomized Study to Compare the Efficacy and Safety of the Zevalin (Ibritumomab Tiuxetan) Therapeutic Regimen Following Cyclophosphamide, Vincristine, Prednisone, and Rituximab (R-CVP) With R-CVP Alone in High-Risk Subjects With Previously Untreated CD20-Positive Follicular Non-Hodgkin's Lymphoma

This study will treat follicular lymphoma patients who have not received previous treatment with R-CVP. Half of the patients will receive Zevalin after R-CVP and the other half will receive only R-CVP. The two patient groups will be compared to determine if Zevalin given after R-CVP therapy provides greater benefits than receiving no additional anti-cancer therapy after R-CVP.

Inclusion Criteria:

• Must give written informed consent and any authorizations required by local law (e.g., Protected Health Information).
• Age greater than or equal to 18 years at the time of informed consent.
• Histologically confirmed follicular NHL according to the Revised European American Lymphoma (REAL)/World Health Organization (WHO)classification (from initial diagnosis); grades 1, 2, or 3.
• Bi-dimensionally measurable lesion(s) in at least one site.
• High risk NHL as defined by a follicular lymphoma international prognostic index (FLIPI) of 3, 4, or 5 assessed within 3 months prior to randomization.
• NHL requires treatment as determined by the investigator.
• Confirmed CD20+ lymphoma cells.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1,or 2.
• Expected survival of greater than or equal to 3 months.
• Male subjects and female subjects of child bearing potential willing to practice effective contraception during the study and willing and able to continue contraception for 1 year after their last dose of study treatment (R CVP for subjects in the observation arm and the Zevalin therapeutic regimen for subjects in the Zevalin arm).

Exclusion Criteria:

• Previous anticancer treatment for NHL, including chemotherapy, immunotherapy, radiation (locoregional or extended field), radioimmunotherapy, or investigational therapy.
• Known seropositivity for hepatitis C virus, hepatitis B virus (surface antigen-positive), or other active infection uncontrolled by treatment.
• Known diagnosis of human immunodeficiency virus infection.
• Presence of primary gastric, central nervous system (CNS), or testicular lymphoma, or transformed lymphoma, or chronic lymphocytic leukemia (CLL).
• Active therapy within previous 5 years for other malignancy, except non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma.
• Abnormal liver function: total bilirubin >1.5 X upper limit of normal (ULN) or ALT >2.5 X ULN.
• Impairment of renal function (serum creatinine >1.5 X ULN) not due to lymphoma.
• Concurrent severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months of study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) that could compromise participation in the study.
• Known hypersensitivity to murine and/or chimeric proteins.
• History of severe allergic or anaphylactic reactions.
• Known allergy to any components present in rituximab, cyclophosphamide, vincristine, and prednisone (CVP), or Zevalin.
• Treatment with another study treatment or approved therapy for investigational use within the 12 weeks prior to randomization.
• Exposure to monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion proteins.
• Females with a positive pregnancy test result at screening or who are currently breastfeeding.
• Inability to comply with study requirements.
• Major surgery within 28 days except for diagnosis.
• In need of immediate intervention to treat life threatening complications.