RATIONALE: Biological therapies, such as CpG 7909, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab and yttrium Y 90 ibritumomab tiuxetan, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving CpG 7909 together with monoclonal antibodies may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of CpG 7909 when given together with rituximab and yttrium Y 90 ibritumomab tiuxetan in treating patients with non-Hodgkin's lymphoma that is recurrent or did not respond to previous treatment.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of CpG 7909 when administered in combination with rituximab and yttrium 90 ibritumomab in patients with CD20+ recurrent or refractory non-Hodgkin's lymphoma.
• Assess the toxicity of this regimen in these patients.

Secondary

• Determine the response rate (complete response [CR], CR unconfirmed, and partial response) in patients treated with this regimen.
• Compare the biodistribution of indium In 111 ibritumomab tiuxetan radioimmunoconjugate scans before and after treatment with CpG 7909.
• Determine the human antimouse antibody and/or human antichimeric antibody rate in patients treated with this regimen.
• Determine if CpG 7909, when given in combination with rituximab and yttrium Y 90 ibritumomab tiuxetan, can stimulate immune effector cells in the blood and tumor tissue of these patients.

OUTLINE: This is a multicenter, dose-escalation study of CpG 7909.

Patients receive rituximab IV on days 1, 8, and 15, CpG 7909 IV over 2 hours on days 6, 13, 20, and 27, and yttrium Y 90 ibritumomab tiuxetan* IV over 10 minutes on day 15 in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on days 1 and 8. Patients undergo whole-body gamma camera imaging, single-photon emission computed tomography/CT scans, and blood sampling after each dose of indium In 111 ibritumomab tiuxetan to determine biodistribution. If biodistribution is acceptable, patients receive yttrium Y 90 ibritumomab tiuxetan.

Cohorts of 6 patients receive escalating doses of CpG 7909 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Twelve additional patients are treated at the MTD.

Blood samples are collected at baseline and periodically during treatment and follow up. Samples are evaluated for immunology correlates by flow cytometry and immunoenzyme techniques.

After the completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed non-Hodgkin's lymphoma, including the following subtypes:

  • Small lymphocytic lymphoma
  • Lymphoplasmacytoid lymphoma
  • Grade 1, 2, or 3 follicular lymphoma
  • Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • Nodal marginal zone B-cell lymphoma
  • Splenic marginal zone B-cell lymphoma
  • Diffuse large cell lymphoma
  • Transformed lymphoma
  • Mantle cell lymphoma
• Recurrent, refractory, or residual disease
• CD20-positive disease
• Bidimensionally measurable disease (≥ 1 lesion that has a single diameter of ≥ 2 cm)
• Must have < 25% bone marrow involvement of cellular marrow with lymphoma, as determined by bilateral bone marrow aspirate and biopsy
• No marrow cellularity ≤ 15% (as determined on all bone marrow samples)
• No prior failed stem cell collection
• No CNS lymphoma
• No lymphoma related to HIV or AIDS
• No myelodysplastic syndromes or marrow chromosomal changes suggesting myelodysplasia

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 150,000/mm³
• Lymphocyte count < 5,000/mm³ (only for patients with small lymphocytic lymphoma)
• Hemoglobin ≥ 8 g/dL
• Total bilirubin ≤ 2 times upper limit of normal (ULN) OR direct bilirubin ≤ 1.5 times ULN
• Creatinine ≤ 2 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious nonmalignant disease (e.g., active infection) or other condition that would preclude study participation
• No other active primary malignancy
• No known human antimouse antibodies or human antichimeric antibodies
• No skin rash (e.g., Stevens-Johnson's syndrome or toxic epidermal necrolysis) after receiving rituximab

• No pre-existing clinical autoimmune or antibody-mediated diseases*, including any of the following:

  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Multiple sclerosis
  • Sjögren's syndrome
  • Autoimmune thrombocytopenia
• NOTE: *If no clinical symptoms, but only previously detected antibodies, then not excluded.

PRIOR CONCURRENT THERAPY:

• More than 1 week since prior filgrastim (G-CSF) or sargramostim (GM-CSF) (3 weeks for pegfilgrastim)
• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 4 weeks since prior major surgery, except for diagnostic surgery
• More than 6 weeks since prior rituximab
• No prior external-beam radiotherapy to > 25% of active bone marrow
• No prior myeloablative therapies with autologous or allogeneic bone marrow transplantation or peripheral blood stem cell support
• No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan, tositumomab, or iodine I 131 monoclonal antibody Lym-1
• No concurrent myelosuppressive chemotherapy
• No concurrent corticosteroid therapy, except prednisone (< 20 mg) for benign causes