• Pharmacokinetics and pharmacodynamics [ Designated as safety issue: No ]
• Safety and tolerability [ Designated as safety issue: Yes ]
• Maximum tolerated dose [ Designated as safety issue: Yes ]

• Pharmacokinetics and pharmacodynamics
• Safety and tolerability
• Maximum tolerated dose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I trial to study the effectiveness of bortezomib in treating patients who have advanced cancer and kidney dysfunction.

OBJECTIVES:

• Determine the pharmacokinetics and pharmacodynamics of bortezomib in patients with advanced malignancies and renal insufficiency.
• Determine the safety and tolerability of this drug in these patients.
• Determine the maximum tolerated dose of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to most recent creatinine clearance (greater than 60 mL/min vs 40-59 mL/min vs 20-39 mL/min vs less than 20 mL/min vs any creatinine clearance and undergoing renal dialysis).

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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 at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of up to 12 patients is treated at the MTD.

PROJECTED ACCRUAL: A total of 60-69 patients (at least 12 per stratum) will be accrued for this study.

• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Unspecified Adult Solid Tumor, Protocol Specific

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy (including non-Hodgkin's lymphoma and multiple myeloma) for which there is no known potentially curative or definitely life-extending therapy
• Measurable or evaluable disease (patients with reliable tumor markers are allowed)

• No symptomatic CNS metastases

  • Brain metastases previously treated with radiotherapy and/or surgery and stable for at least 8 weeks are eligible

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN (5 times ULN if liver involvement present)

Renal

• Abnormal kidney function allowed
• No dialysis within 4 hours of study drug

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No New York Heart Association class III or IV heart disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 30 days after study participation
• No preexisting neuropathy grade 2 or greater
• No psychiatric illness or social situation that would preclude study compliance
• No ongoing or active infection
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior immunotherapy
• More than 4 weeks since prior biologic therapy
• No concurrent immunotherapy
• No concurrent thalidomide

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No concurrent chemotherapy

Endocrine therapy

• Concurrent steroids for CNS metastases allowed provided dose is stable

Radiotherapy

• See Disease Characteristics
• More than 2 weeks since prior radiotherapy

• No prior radiotherapy to more than 50% of the bone marrow

  • Prior total body irradiation for bone marrow or stem cell transplantation allowed
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• No prior bortezomib
• No concurrent antiretroviral therapy for HIV-positive patients
• No concurrent enzyme-inducing anticonvulsants for patients with brain metastases

• No other concurrent investigational agents

  • Bisphosphonates (e.g., pamidronate or zoledronate) not considered investigational
• No concurrent bisphosphonates on days 1, 4, 8, and 11 of course 1