• Overall response rate (combined complete response and partial response) [ Designated as safety issue: No ]
  

• Safety [ Designated as safety issue: Yes ]
  
• Tolerability [ Designated as safety issue: Yes ]
  
• Time to disease progression [ Designated as safety issue: No ]
  
• Possible mechanism of resistance [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the overall response rate in patients with chemotherapy-refractory diffuse large B-cell lymphoma treated with bortezomib.
• Determine the safety and tolerability of this drug in these patients.
• Determine the time to disease progression in patients treated with this drug.
• Determine the possible mechanism of resistance to this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 20 days and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 22-40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell lymphoma, meeting criteria for 1 of the following:

  • Relapsed after prior high-dose chemotherapy with stem cell support
  • Relapsed after prior chemotherapy, including at least 1 prior standard non-Hodgkin's chemotherapy regimen, but not a candidate for high-dose chemotherapy with stem cell support

• Measurable disease

  • At least 1 bidimensionally measurable lesion at least 1.5 cm by CT scan
• No primary or secondary CNS lymphoma
• No HIV-related lymphoma
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• Hemoglobin at least 9 g/dL

• Absolute neutrophil count at least 1,000/mm^3

  • No colony-stimulating factors within 4 weeks before obtaining this result

• Platelet count at least 50,000/mm^3

  • No platelet transfusion within 4 weeks before obtaining this result

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN
• No active hepatitis B or C viral infection

Renal

• Creatinine no greater than 2 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• No evidence of acute ischemia or new conduction system abnormalities on EKG
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Sodium greater than 130 mEq/L
• HIV negative
• No ongoing or active infection
• No other concurrent uncontrolled illness that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance
• No prior allergic reaction attributable to compounds of similar chemical or biological composition to bortezomib

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• See Chemotherapy
• At least 4 weeks since prior immunotherapy

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy
• More than 12 weeks since prior high-dose chemotherapy with hematopoietic stem cell support

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery unless fully recovered

Other

• Recovered from prior therapy
• No other concurrent investigational agents
• No other concurrent investigational or commercial agents or therapies to treat the malignancy