A Phase 3 Open-label Multicenter Randomized Study to Compare the Efficacy and Safety of Zevalin Therapeutic Regimen Following R CVP With R CVP Alone in High Risk Subjects With Previously Untreated CD20 Positive Follicular Non Hodgkin's Lymphoma
- 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
- Previous anticancer treatment for NHL, including chemotherapy, immunotherapy,
radiation (locoregional or extended field), radioimmunotherapy, or investigational
- 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
- Inability to comply with study requirements.
- Major surgery within 28 days except for diagnosis.
- In need of immediate intervention to treat life threatening complications.