RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Radiolabeled monoclonal antibodies can locate and deliver radioactive cancer-killing substances.

PURPOSE: Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibodies with rituximab in treating patients who have non-Hodgkin's lymphoma that has not responded to high-dose chemotherapy and autologous stem cell transplantation.

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90-labeled ibritumomab tiuxetan when administered with rituximab in patients with B-cell non-Hodgkin's lymphoma who have relapsed after high-dose chemotherapy and autologous hematopoietic stem cell transplantation.
• Determine the safety and efficacy of this regimen in these patients.

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

• Phase I: Patients receive rituximab IV over 4-6 hours followed by indium In 111-labeled ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0. Patients receive rituximab IV again on day 7 followed by IDEC-Y2B8 IV over 10 minutes.

Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 6 patients experience dose-limiting toxicity.

• Phase II: Once the MTD is determined, 58 additional patients are treated at that dose level as in phase I.

Patients are followed at 6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 78 patients (20 for phase I and 58 for phase II) will be accrued for this study within 2 years.

Inclusion Criteria:

• Diagnosis of relapsed B-cell non-Hodgkin's lymphoma (NHL) after high-dose chemotherapy and autologous stem cell transplantation

• Less than 25% bone marrow involvement with NHL as evidenced by unilateral or bilateral biopsy within the past 6 weeks

  o Bone marrow biopsy should demonstrate 15-20% of cellular space occupied by normal hematopoiesis

• CD20 antigen expression in tumor tissue within the past year as evidenced by 1 of the following:

  • Immunoperoxidase stains of tissue showing positive reactivity with L26 antibody
  • Flow cytometry studies

• Measurable disease

  o More than 2 cm bidimensionally

• 19 years of age and over

• Performance status WHO 0-2

• Life expectancy at least 3 months

• Absolute neutrophil count greater than 1,500/mm^3

• Platelet count greater than 150,000/mm^3

• Bilirubin less than 2.0 mg/dL

• SGOT or SGPT no greater than 2.5 times upper limit of normal (unless due to lymphomatous infiltration of the liver)

• Creatinine less than 2.0 mg/dL

• Fertile patients must use effective contraception during and for 6 months after study therapy

• HIV negative

• At least 4 weeks since prior growth factors

• At least 4 weeks since prior biologic therapy

• At least 4 weeks since any prior cytotoxic chemotherapy (6 weeks for nitrosoureas)

• At least 4 weeks since prior radiotherapy

• Recovered from all prior therapy

• At least 4 weeks since prior immunosuppressants

Exclusion Criteria:

• No active CNS lymphoma
• No HIV- or AIDS-related lymphoma
• No transfusion dependency
• No active obstructive hydronephrosis
• Not pregnant or nursing/negative pregnancy test
• No active infection requiring oral or IV antibiotics
• No human antimurine antibody positivity
• No other major medical problems
• No dependency on hematopoietic growth factors (e.g., epoetin alfa, interleukin-11, filgrastim [G-CSF], or sargramostim [GM-CSF])
• No prior radioimmunotherapy
• No other concurrent biologic therapy of any kind
• No prior fludarabine
• No concurrent chemotherapy
• No concurrent steroids except as maintenance for non-cancerous disease
• No prior pelvic radiotherapy
• No prior radiotherapy to more than 25% of estimated bone marrow reserve
• No concurrent external beam radiotherapy
• No other concurrent investigational drugs
• No other concurrent anti-cancer therapy