Y 90 Ibritumomab Tiuxetan &Rituximab Relapsed or Refractory Diffuse Large B-Cell Non-Hodgkin's Lymphoma

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 ( central nervous system)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.

Eligibility Criteria:
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