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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Lymphoma, Follicular, Follicular Lymphoma

Intervention / Treatment
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* Drug: Zevalin Therapeutic Regimen
* Drug: R-CVP


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive standard R-CVP followed by Zevalin Therapeutic Regimen (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). | Drug: Zevalin Therapeutic Regimen<br>* 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<br>Drug: R-CVP<br>* Standard R-CVP<br>|
| Active Comparator: 2<br>Participants will receive standard R-CVP. | Drug: R-CVP<br>* Standard R-CVP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious and Non-serious Adverse Events |  | 18 months |