• Maximum tolerated dose of bortezomib [ Designated as safety issue: Yes ]
  
• Dose-limiting toxicity [ Designated as safety issue: Yes ]
  

• Response rate [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of bortezomib in combination with rituximab and yttrium Y 90 ibritumomab tiuxetan in patients with relapsed or refractory low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma.
• Determine the dose-limiting toxicity of this regimen in these patients.

Secondary

• Determine the response rate in patients treated with this regimen.

OUTLINE: This is a multicenter, open-label, nonrandomized, dose-escalation study of bortezomib.

Patients receive rituximab IV over 4 hours followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 to assess biodistribution. Patients without altered biodistribution receive rituximab IV over 4 hours followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Patients also receive bortezomib IV over 3-5 seconds on days 4, 8, 11, and 15.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients may be treated at the MTD.

After completion of study treatment, patients are followed every 3 months for 18 months and then every 6 months thereafter.

DISEASE CHARACTERISTICS:

• Histologically confirmed low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma

  • Bone marrow biopsy required for pretreatment evaluation

    • Unilateral bone marrow biopsy allowed
    • Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping
• Relapsed or refractory disease as defined by disease progression after initial complete response (CR) or failure to achieve CR
• No bone marrow involvement ≥ 25% within the past 30 days
• No pleural effusion or significant ascites
• No active CNS involvement

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• Platelet count ≥ 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• AST ≤ 2.5 times upper limit of normal (ULN)
• Total bilirubin ≤ 2.5 times ULN
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Hepatitis B surface antigen negative
• No current infection with hepatitis B virus
• No HIV positivity
• No neuropathy or neuropathic pain ≥ grade 2
• No history of allergic reaction to boron or mannitol
• No active serious infection or medical or psychiatric illness that would preclude study therapy

• No other malignancy within the past 5 years except for the following:

  • Basal cell or squamous cell carcinoma of the skin that has been completely resected
  • In situ malignancy that has been completely resected
  • T1-T2a, N0, M0 prostate cancer treated with a prostatectomy or radiotherapy within the past 2 years with an undetectable PSA level

• No other condition, including any of the following:

  • Myocardial infarction within the past 6 months
  • New York Heart Association class III-IV heart failure
  • Uncontrolled angina
  • Severe uncontrolled ventricular arrhythmias
  • Electrocardiographic evidence of acute ischemia or active conduction system abnormalities

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgical resection of malignancy

  • No limitations on the number of prior therapies
• More than 4 weeks since prior major surgery
• More than 14 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF)

• More than 14 days since prior and no other concurrent investigational agents

  • Concurrent participation in a nontreatment study allowed
• No prior radioimmunotherapy