Phase II trial to study the effectiveness of bortezomib in treating patients who have low-grade lymphoproliferative disorders. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PRIMARY OBJECTIVES:

I. Determine the frequency and duration of complete and partial response rates in patients with grade I, II, or III follicular lymphoma or mantle cell lymphoma treated with bortezomib.

SECONDARY OBJECTIVES:

I. Determine the response of minimal residual disease by polymerase chain reaction (PCR) detectable or clonotypic PCR minimal residual disease in bone marrow of patients treated with this regimen.

II. Determine the time to progression and overall survival of patients treated with this regimen.

III. Determine the toxic effects of this regimen in these patients.

OUTLINE: Patients are stratified according to disease type (follicular lymphoma vs mantle cell lymphoma).

Patients receive an infusion of bortezomib over 3-5 seconds once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.

Patients are followed every 3 months for 1 year and then every 4 months for 2 years.

Inclusion Criteria:

• Histologically or cytologically confirmed lymphoproliferative disorder of 1 of the following subtypes:

• * Relapsed or refractory grade I, II, or III follicular center cell lymphoma

  • Relapsed or refractory mantle cell lymphoma

• Measurable disease for non-Hodgkin's lymphoma (NHL) only

  • At least 1 unidimensionally measurable lesion
  • At least 2 cm by conventional techniques OR at least 1 cm by spiral CT scan
  • Lymph nodes no greater than 1 cm in short axis considered normal

• Absolute lymphocytosis greater than 5,000/mm^3 with B-cell phenotype (CD19, 20,or 23 positive) with more than 30% bone marrow lymphocytes for CLL or other leukemic forms of NHL

• No known brain metastases

• Performance status - Karnofsky 70-100%

• At least 3 months

• See Disease Characteristics

• Absolute neutrophil count greater than 1,500/mm^3 (500/mm^3 if lymphomatous involvement of bone marrow)

• Platelet count greater than 50,000/mm^3

• Bilirubin less than 1.5 times upper limit of normal (ULN)

• AST and ALT no greater than 2.5 times ULN (4 times ULN in case of liver metastases)

• Creatinine less than 1.5 times ULN

• No symptomatic congestive heart failure

• No New York Heart Association class III or IV heart disease

• No unstable angina pectoris

• No cardiac arrhythmia

• No myocardial infarction within the past 6 months

• No cerebrovascular accident or transient ischemic attack within the past 6 months

• No history of orthostatic hypotension

• No evidence of acute ischemia or significant conduction abnormality (left anterior hemiblock in the presence of right bundle branch block or second or third degree atrioventricular blocks) on electrocardiogram

• No uncontrolled hypertension requiring antihypertensive medication

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Febrile episodes up to 38.5°C allowed if no evidence of active infection

• No other uncontrolled concurrent illness

• No known or active HIV infection

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study entry

• At least 3 months since prior monoclonal antibody therapy (e.g., rituximab)

• No more than 3 prior regimens of conventional cytotoxic chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• At least 1 week since prior steroid therapy

• At least 4 weeks since prior radiotherapy and recovered

• At least 4 weeks since prior major surgery

• No other concurrent investigational agents