Study of Zevalin Versus Observation in Participants at Least 60 Years Old With Newly Diagnosed Diffuse Large B-cell Lymphoma in Positron Emission Tomography (PET)-Negative Complete Remission After Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) or R-CHOP-like Therapy
Condition: Diffuse Large B-cell Lymphoma; Follicle Center Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular
Intervention: Zevalin; Y-90-Zevalin; Rituximab; In-111 Zevalin
Intervention description: Zevalin administered intravenous infusion.; Y-90-Zevalin administered by intravenous infusion.; Rituximab administered by intravenous infusion.; In-111-Zevalin administered by intravenously.
Intervention MeSH terms: Rituximab; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 79.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy and safety of Zevalin compared with
      observation alone in participants who are in PET-negative complete remission after first-line
      R-CHOP or R-CHOP like therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participant was 60-years of age or older at time of randomization

          2. Histologically confirmed Ann Arbor stage II, III, or IV diffuse large B-cell lymphoma
             (DLBCL); or follicular lymphoma (FCL) Grade 3B according to the Revised European
             American lymphoma (REAL)/ World health organization (WHO) classification (from initial
             diagnosis made prior to starting R-CHOP therapy. Results from a pre R-CHOP marrow
             shall be available for review.

          3. Local pathology review confirming the DLBCL diagnosis and cluster of differentiation
             20 (CD20) positivity, and no evidence of DLBCL in bone marrow upon confirmation of
             complete remission (CR).

          4. A paraffin block or original slides available for confirmatory pathology review.
             Participants may be randomized based on the local pathology result.

          5. Age-adjusted international prognostic index (IPI) of 1, 2, or 3. The age-adjusted IPI
             was defined by one point for Lactate dehydrogenase (LDH) > upper limit of normal
             (ULN); Stage III or IV; and Karnofsky performance status <80% or WHO/ eastern
             cooperative operations group (ECOG) performance status >1.

          6. First-line treatment of DLBCL must have been 6 cycles of standard R-CHOP21, R-CHOP14
             or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin,
             and rituximab (DA-EPOCH-R) chemotherapy. Participants who received pre-phase therapy
             for the purpose of improving performance status prior to initiating R-CHOP are
             eligible.

          7. Complete remission (CR) according to the International Workshop Response Criteria for
             non-Hodgkin's lymphoma (NHL) described by Cheson et al after first-line treatment.
             Computerized tomography (CT) scans of chest, abdomen, pelvis, and neck (if applicable)
             must have been performed within 6 weeks after the last dose of the last course of
             chemotherapy. Applicability of the neck CT means that the participant had involvement
             of the neck region by palpation / physical examination at first diagnosis.

          8. A negative Fluorine-18-deoxyglucose positron emission tomography (FDG-PET) scan
             confirming complete response, with negative defined as a score of 1-3 on the Deauville
             5-point scale used to quantify radionucleotide density in PET scans as determined
             locally (Morschhauser 200735).

          9. Bone marrow cellularity greater than 15%, no evidence of myelodysplasia
             morphologically and no evidence of involvement with lymphoma either at the pre R-CHOP
             marrow or on repeat assessment pre-Zevalin. After completing R-chemotherapy, a repeat
             marrow is required for participant randomized to the Zevalin arm only.

         10. A world health organization/eastern cooperative oncology group (WHO/ECOG) performance
             status of 0, 1 or 2.

         11. Adequate hematopoietic functions: Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/ liter
             (L), Hemoglobin (Hgb) ≥ 9 g/dL, Platelets ≥ 100 x 10^9/L.

         12. Life expectancy of 6 months or longer.

         13. Written informed consent obtained according to local guidelines.

        Exclusion Criteria:

          1. Presence of any other malignancy or history of prior malignancy within 5 years of
             study entry. Within 5 years, participants treated for Stage I or II cancers are
             eligible provided they have a life expectancy of > 5 years. The 5-year exclusion rule
             does not apply to-non melanoma skin tumors and in situ cervical cancer.

          2. Prior radioimmunotherapy, including radiation therapy for Non-Hodgkin's lymphoma) NHL,
             or any other NHL therapy.

          3. Presence of primary gastric, central nervous system (CNS), or testicular lymphoma at
             first diagnosis.

          4. Histological transformation of low-grade NHL.

          5. Active hepatitis B or C.

          6. Known history of human immunodeficiency virus (HIV) infection.

          7. Abnormal liver function: total bilirubin > 2 × ULN unless secondary to Gilbert
             disease.

          8. Abnormal renal function: serum creatinine > 2.0 × ULN.

          9. Non-recovery from the toxic effects of chemotherapy to < grade 2, or interfering with
             Zevalin treatment.

         10. Known hypersensitivity to murine or chimeric antibodies or proteins.

         11. Granulocyte-colony stimulating factor (G-CSF) or Granulocyte macrophage-colony
             stimulating factor (GM-CSF) therapy within 4 weeks prior to Zevalin or observation.

         12. Concurrent severe and/or medically uncontrolled 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)
             which could compromise participation in the study.

         13. Treatment with investigational drugs less than 4 weeks prior to Zevalin or
             observation.

         14. Major surgery less than 4 weeks prior to Zevalin or start of observation.

         15. Concurrent systemic corticosteroid use for any reason except as premedication in case
             of known or suspected allergies to contrast media or as premedication for potential
             side effects of rituximab treatment. Participants on a chronic dose of prednisone for
             a medical condition (e.g. Asthma or autoimmune disease) less than or equal to 20
             milligram (mg) daily, stable for 4 weeks, are permissible.

         16. Unwillingness or inability to comply with the protocol.