• Response rate (complete response, unconfirmed complete response, and partial response) at 12 weeks [ Designated as safety issue: No ]
• Event-free survival [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]

• Response rate (complete response, unconfirmed complete response, and partial response) at 12 weeks
• Event-free survival
• Overall survival

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. Combining yttrium Y 90 ibritumomab tiuxetan with rituximab may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining yttrium Y 90 Ibritumomab tiuxetan with rituximab in treating patients who have relapsed or refractory diffuse large B-cell non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine the best overall response in patients with relapsed or refractory diffuse large B-cell non-Hodgkin's lymphoma treated with yttrium Y 90 ibritumomab tiuxetan and rituximab.
• Determine the event-free survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

• Radioimmunotherapy: Patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 (for imaging only); yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8; and rituximab IV over 3-4 hours on days 1, 8, 15, 22, 29, and 36.
• CNS prophylaxis: Patients receive CNS prophylaxis comprising intrathecal (IT) methotrexate or IT cytarabine on days 15, 22, 29, and 36 OR IT cytarabine (liposomal) on days 15 and 29.
• Maintenance rituximab: Patients are assessed for response at week 14. Beginning at month 6, patients with stable or responding disease receive maintenance therapy comprising rituximab IV over 3-4 hours once weekly for 4 weeks. Maintenance therapy repeats every 6 months for 2 years (total of 4 courses) in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.

• Biological: rituximab
• Drug: cytarabine
• Drug: liposomal cytarabine
• Drug: methotrexate
• Radiation: yttrium Y 90 ibritumomab tiuxetan

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma, including any of the following:

  • B-cell diffuse large cell variant
  • Immunoblastic
  • Mediastinal (thymic) large cell
  • T-cell/histiocyte-rich
  • Anaplastic large B-cell
  • Intravascular large B-cell
  • Lymphomatoid granulomatosis

• Relapsed or refractory disease after at least 1 prior chemotherapy regimen and requires further treatment

  • Relapsed disease, defined as the following:

    • Appearance of any new lesion OR increase of at least 50% in the size of a previously involved site
    • 50% increase in greatest diameter of any previously identified node greater than 1 cm in the short axis OR in the sum of the perpendicular diameter (SPD) of more than 1 node

  • Progressive disease, defined as the following:

    • 50% increase from nadir in the SPD of any previously identified abnormal node
    • Appearance of any new lesion during or at the end of therapy
• CD20-positive disease by immunohistochemistry

• Bidimensionally measurable disease

  • At least 1 lesion at least 2.0 cm by CT scan
• Less than 25% bone marrow involvement by lymphoma
• No transformed lymphoma from indolent to aggressive
• No HIV- or AIDS-related lymphoma
• No hypocellular bone marrow
• No marked reduction in bone marrow precursors of 1 or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid)
• No CNS lymphoma
• Ineligible for myeloablative therapy OR refused transplantation
• Ineligible for any other open yttrium Y 90 ibritumomab tiuxetan investigational protocols

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Lymphocyte count no greater than 5,000/mm^3 (for patients with small lymphocytic lymphoma)
• Platelet count at least 100,000/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 participation
• No concurrent serious nonmalignant disease or infection that would preclude study participation
• No human antimurine antibody reactivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior autologous bone marrow transplantation
• No prior peripheral blood stem cell rescue
• No prior failed stem cell collection
• Prior rituximab within the past 90 days allowed provided patient has fludeoxyglucose-avid disease that is also indium In 111 ibritumomab tiuxetan-avid disease in at least 1 lesion
• More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• No prior radioimmunotherapy
• No prior external beam radiotherapy (involved field or regional) to more than 25% of active bone marrow

Surgery

• More than 4 weeks since prior major surgery (except diagnostic surgery)

Other

• Recovered from all prior therapy
• More than 4 weeks since prior therapy for lymphoma
• More than 8 weeks since prior phase II investigational drugs
• No other concurrent antineoplastic therapy