RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary
for cancer cell growth.
PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who
have diffuse large B-cell lymphoma that is refractory to previous chemotherapy.
- 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
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.
- Histologically confirmed diffuse large B-cell lymphoma, meeting criteria for 1 of the
- 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
- 18 and over
- ECOG 0-2 OR
- Karnofsky 60-100%
- More than 3 months
- 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
- 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
- Creatinine no greater than 2 times ULN OR
- Creatinine clearance at least 60 mL/min
- 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
- 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:
- See Disease Characteristics
- See Chemotherapy
- At least 4 weeks since prior immunotherapy
- See Disease Characteristics
- More than 4 weeks since prior chemotherapy
- More than 12 weeks since prior high-dose chemotherapy with hematopoietic stem cell
- Not specified
- More than 4 weeks since prior radiotherapy
- No concurrent radiotherapy
- More than 4 weeks since prior major surgery unless fully recovered
- Recovered from prior therapy
- No other concurrent investigational agents
- No other concurrent investigational or commercial agents or therapies to treat the