OBJECTIVES:

• Determine the safety and tolerability of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8) in patients with post-transplant lymphoproliferative disorder.
• Determine the safety and toxicity profile of IDEC-Y2B8 and rituximab in these patients.
• Correlate the Epstein-Barr virus viral load with response and relapse in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8).

• Phase I: Patients receive rituximab IV and indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients undergo 2 (or 3 if needed) imaging scans between days 1-6. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by IDEC-Y2B8 IV over 10 minutes on day 8.

Cohorts of 6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive treatment as in phase I at the MTD of IDEC-Y2B8. 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 13-28 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed post-transplant lymphoproliferative disorder (PTLD) of 1 of the following stages:

  • Stage III or IV
  • Localized (not amenable to localized radiotherapy or excision)
  • Recurrent

• The following histologies* are eligible:

  • Polyclonal PTLD
  • Monoclonal PTLD
  • Diffuse large B-cell non-Hodgkin's lymphoma (NHL)
  • Lymphoplasmacytic NHL
  • Burkitt/Burkitt-like NHL NOTE: *Must be B-cell and CD20+

• Must not have completely responded during OR progressed after prior rituximab with or without chemotherapy

  • No history of rapid disease progression while receiving prior chemotherapy
• Measurable disease
• Must have less than 25% bone marrow involvement with lymphoma
• Prior solid organ transplantation required

• Evaluation of malignant cells for Epstein-Barr virus (EBV) required

  • EBV positive or negative allowed
• No pleural effusion
• No CNS lymphoma, including leptomeningeal disease
• No pulmonary involvement by NHL in patients with prior lung transplantation
• No HIV or AIDS-related lymphoma
• No hypocellular bone marrow (i.e., less than 15% cellularity)
• No marked reduction in bone marrow precursors of one or more cell lines (i.e., granulocytic, megakaryocytic, or erythroid)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 50-100%

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3

Hepatic

• Bilirubin no greater than 2.5 mg/dL

Renal

• Creatinine no greater than 2.5 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• HIV negative
• No serious nonmalignant disease or infection that would compromise study objectives
• No presence of antimurine antibody reactivity
• No other concurrent active malignancy requiring therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• More than 6 weeks since prior rituximab
• No prior allogeneic bone marrow or hematopoietic stem cell transplantation
• No prior radioimmunotherapy for NHL

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Biologic therapy
• No prior radiotherapy to more than 25% of active bone marrow (involved field or regional)

Surgery

• See Disease Characterisics
• More than 4 weeks since prior major surgery except diagnostic surgery

Other

• No other concurrent anticancer therapy