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

• To determine the Maximum Tolerated Dose (MTD) of the combination of bortezomib and ibritumomab tiuxetan in patients with recurrent/refractory mantle cell and low-grade, or follicular B-Cell non-Hodgkin’s lymphoma.
• To identify the dose limiting toxicities associated with the combination of ibritumomab tiuxetan and bortezomib in patients with recurrent/refractory mantle cell and low-grade, or follicular B-Cell non-Hodgkin’s lymphoma.

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, and radiolabeled monoclonal antibodies, such as 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 without harming normal cells. Giving bortezomib together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with rituximab and yttrium Y 90 ibritumomab tiuxetan in treating patients with relapsed or refractory low-grade, follicular, or mantle cell non-Hodgkin's lymphoma.

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.

• Biological: rituximab
• Drug: bortezomib
• Radiation: yttrium Y 90 ibritumomab tiuxetan

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