• Overall response rate [ Designated as safety issue: No ]
• Duration of response [ Designated as safety issue: No ]

• Overall response rate
• Duration of response

• Complete response (CR), unconfirmed CR, and partial response [ Designated as safety issue: No ]
• Event-free survival [ Designated as safety issue: No ]
• Time to progression [ Designated as safety issue: No ]
• Time to next lymphoma treatment [ Designated as safety issue: No ]

• Complete response (CR), unconfirmed CR, and partial response
• Event-free survival
• Time to progression
• Time to next lymphoma treatment

RATIONALE: Monoclonal antibodies such as yttrium Y 90 ibritumomab tiuxetan and rituximab can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells.

PURPOSE: This phase II trial is studying how well giving yttrium Y 90 ibritumomab tiuxetan together with rituximab works in treating patients with progressive non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine the efficacy of yttrium Y 90 ibritumomab tiuxetan and rituximab, in terms of overall response rate (complete, unconfirmed complete, and partial) and duration of response, in patients with transformed CD20+ B-cell non-Hodgkin's lymphoma.
• Determine the safety of this regimen in these patients.
• Determine the event-free survival and time to treatment progression in patients treated with this regimen.
• Determine the immunogenicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV followed within 4 hours by indium In 111 ibritumomab tiuxetan IV (for imaging) over 10 minutes on day 1. Patients undergo 1 (or 2 if needed) imaging scan between days 2-5. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8.

Patients are followed monthly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 18-24 months.

• Biological: rituximab
• Radiation: yttrium Y 90 ibritumomab tiuxetan

DISEASE CHARACTERISTICS:

• Histologically confirmed transformed CD20+ B-cell non-Hodgkin's lymphoma (NHL)

  • Transformation defined as:

    • Progression to a more aggressive diffuse lymphoma, excluding conversion to a more aggressive grade of follicular lymphoma (e.g., WHO/REAL follicular center, large, grade III NHL)
  • Initial large cell follicular lymphoma must progress to a diffuse large cell lymphoma
  • De novo transformed NHL ineligible

• Requiring treatment as determined by any of the following characteristics:

  • An increase in overall tumor size
  • Presence of B symptoms
  • Presence of masses that are causing ongoing clinical symptomatology
• Must have less than 25% bone marrow involvement with lymphoma
• Must have received and either relapsed or failed to respond to prior therapy for initial low grade or follicular NHL

• Must have bidimensionally measurable disease defined as:

  • Greater than 2 cm OR 1.5 cm if 0.5 cm slices are used during spiral CT scan

  • Nonmeasurable disease includes any of the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural or pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
    • Lesions that are situated in a previously irradiated area

• No expected impairment in bone marrrow reserve meeting any of the following criteria:

  • Platelet count less than 150,000/mm^3
  • Hypocellular bone marrow (less than 15% cellularity)
  • Marked reduction in bone marrow precursors of one or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid)
  • History of failed stem cell collection

• Patients with peritoneal invasion and/or ascites with positive cytology for lymphoma OR pleural invasion and/or effusion with positive cytology for lymphoma are eligible only if their effusion or ascites can be tapped dry

  • No significant remaining malignant effusion or ascites at the time of study drug administration
• No known meningeal lymphoma or known parenchymal CNS lymphoma NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 1,500/mm^3
• Lymphocyte count no greater than 5,000/mm^3
• Platelet count at least 150,000/mm^3

Hepatic

• Bilirubin no greater than 2.0 mg/dL

Renal

• Creatinine no greater than 2.0 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 year after study treatment
• HIV negative
• No other malignancy except nonmelanoma skin cancer unless patient has completed therapy and is considered to be at less than 30% risk of relapse
• No human anti-mouse antibody (HAMA) reactivity (patients with prior exposure to murine antibodies)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Radiotherapy
• At least 3 weeks since prior anticancer immunotherapy (6 weeks for rituximab) and recovered
• More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• No prior myeloablative therapy with bone marrow transplantation or peripheral blood stem cell rescue

Chemotherapy

• See Biologic therapy
• At least 3 weeks since prior anticancer chemotherapy (6 weeks for nitrosourea or mitomycin) and recovered

Endocrine therapy

• No concurrent systemic corticosteroids with either of the following dose schedules:

  • No greater than 50 mg of prednisone as a single dose (or equivalent)
  • No greater than 50 mg of prednisone per dose (or equivalent) for more than 6 doses

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior anticancer radiotherapy and recovered
• No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan
• No prior external beam radiotherapy to more than 25% of active bone marrow (involved field or regional)

Surgery

• At least 3 weeks since prior anticancer surgery and recovered
• More than 4 weeks since prior major surgery (other than diagnostic surgery)

Other

• At least 3 weeks since other prior anticancer therapy and recovered

• National Cancer Institute (NCI)
• Southwest Oncology Group
• Eastern Cooperative Oncology Group