Phase 3 Study of Zevalin Following R-CVP in Previously Untreated Patients With Follicular Non Hodgkin's Lymphoma (NHL)
Condition: Follicular Lymphoma; Lymphoma, Follicular
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin
Intervention: Zevalin Therapeutic Regimen; R-CVP
Intervention description: Day 1: 250 mg/m2 Rituxan followed by 5 mCi 111In Zevalin. Day 7: 250 mg/m2 Rituxan followed by 0.4 mCi/kg Zevalin; Standard R-CVP
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.