Bortezomib, 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.

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