• Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
• Toxicity (Phase I) [ Designated as safety issue: Yes ]
• Proportion of patients who receive 2 sequential doses of Y2B8 immunotherapy and are progression-free at 3 years (Phase II) [ Designated as safety issue: No ]

• Maximum tolerated dose (Phase I)
• Toxicity (Phase I)
• Proportion of patients who receive 2 sequential doses of Y2B8 immunotherapy and are progression-free at 3 years (Phase II)

• Association between the amount of tumor radiation indicated by the In2B8 scan and tumor response (Phase I) [ Designated as safety issue: No ]
• Association between In2B8 scan and positron emission tomography scan results (Phase I) [ Designated as safety issue: No ]
• Appearance of tumor and normal organ images on the second In2B8 scan (Phase I) [ Designated as safety issue: No ]
• Survival (Phase II) [ Designated as safety issue: No ]
• Time to disease progression (Phase II) [ Designated as safety issue: No ]
• Tumor response rate (Phase II) [ Designated as safety issue: No ]

• Association between the amount of tumor radiation indicated by the In2B8 scan and tumor response (Phase I)
• Association between In2B8 scan and positron emission tomography scan results (Phase I)
• Appearance of tumor and normal organ images on the second In2B8 scan (Phase I)
• Survival (Phase II)
• Time to disease progression (Phase II)
• Tumor response rate (Phase II)

RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Biological therapies such as filgrastim and interleukin-11 use different ways to stimulate the immune system and stop cancer cells from growing.

PURPOSE: Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibody therapy and rituximab with and without filgrastim and interleukin-11 in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of yttrium Y 90 ibritumomab tiuxetan (IDEC-^90Y2B8) administered with rituximab with and without filgrastim (G-CSF) and interleukin-11 (IL-11) in patients with relapsed low-grade or follicular CD20+ non-Hodgkin's lymphoma. (Phase I)
• Determine the toxicity of this regimen in these patients.
• Determine the response rate in patients treated with this regimen.
• Compare tumor and normal organ dosimetry with positron emission tomography and computerized tomography scans, subsequent tumor response, and normal organ toxicity by utilizing indium In 111 ibritumomab tiuxetan radioimmunoconjugate scans before each IDEC-^90Y2B8 dose in these patients. (Phase I)
• Determine the immune response to this regimen, in terms of human anti-mouse and human anti-chimeric antibody formation, in these patients. (Phase I)
• Determine whether G-CSF and IL-11 can ameliorate the effect of the MTD of IDEC-^90Y2B8 on bone marrow function in these patients. (Phase I)
• Determine progression-free survival at 3 years. (Phase II)

OUTLINE: This is a phase I dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-^90Y2B8) followed by a phase II open-label study.

• Phase I: Patients receive rituximab IV on days 1 and 8, indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 (for radioimaging), and IDEC-^90Y2B8 IV over 10 minutes on day 8. Treatment repeats 24-36 weeks later for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) of IDEC-^90Y2B8 is determined, patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning when absolute neutrophil count is less than 1,500/mm^3 and continuing until blood counts recover. Patients also receive interleukin-11 (IL-11) SC beginning when platelet count is less than 75,000/mm^3 and continuing until blood counts recover. Patients undergo PBSC transplantation only if marrow recovery is inadequate.

Cohorts of 3-6 patients receive escalating doses of IDEC-^90Y2B8 until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, additional patients are accrued to determine the MTD of this radioimmunotherapy with the addition of the prophylactic cytokines, G-CSF and IL-11.

• Phase II: Patients receive rituximab, indium In 111 ibritumomab tiuxetan, and IDEC-^90Y2B8 IV as determined at the MTD in phase I. Treatment repeats 24-36 weeks later for a total of 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 73 patients will be accrued for this study.

• Biological: filgrastim
• Biological: recombinant interleukin-11
• Biological: rituximab
• Radiation: yttrium Y 90 ibritumomab tiuxetan

DISEASE CHARACTERISTICS:

• Histologically proven relapsed or refractory low-grade or follicular CD20+ non-Hodgkin's lymphoma, including 1 of the following:

  • Small lymphocytic lymphoma
  • Lymphoplasmacytoid lymphoma
  • Follicular center lymphoma (grades I, II, and III)
  • Extranodal marginal zone B-cell lymphoma
  • Nodal marginal zone B-cell lymphoma
  • Splenic marginal zone B-cell lymphoma (monocytoid B-cell lymphoma)
• Bidimensionally measurable disease with at least 1 lesion ≥ 2 cm in the greatest diameter
• Less than 25% bone marrow involvement of cellular marrow with lymphoma by bilateral bone marrow aspirate and biopsy
• No CNS lymphoma
• No myelodysplastic syndromes or marrow chromosomal changes suggesting myelodysplasia
• No HIV or AIDS-related lymphoma
• No pleural effusion or ascites with lymphoma cells 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:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 150,000/mm^3
• Total lymphocyte count < 5,000/mm^3 for patients with small lymphocytic lymphoma

Hepatic:

• Bilirubin ≤ 2 mg/dL

Renal:

• Creatinine ≤ 2 mg/dL

Other:

• No active infection
• No other serious non-malignant disease that would preclude study participation
• No other active primary malignancy
• No known human anti-mouse or human anti-chimeric antibody
• No prior skin rash (e.g., Stevens-Johnson's syndrome or toxic epidermal necrolysis) from rituximab therapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan or iodine I 131 monoclonal antibody tositumomab or Lym-1
• No prior myeloablative therapy with autologous or allogeneic bone marrow transplantation or peripheral blood stem cell support

Chemotherapy:

• See Biologic therapy

Endocrine therapy:

• No concurrent corticosteroid therapy except prednisone (or an equivalent) for adrenal failure or < 20 mg of prednisone daily

Radiotherapy:

• No prior external beam radiotherapy to > 25% of active bone marrow

Surgery:

• More than 4 weeks since prior surgery other than diagnostic surgery

Other:

• No other concurrent myelosuppressive antineoplastic agents