Phase II Study of PS-341 in Low Grade Lymphoproliferative Disorders

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