A Phase II Study of the Novel Proteasome Inhibitor Bortezomib in Combination With Rituximab, Cyclophosphamide and Prednisone in Patients With Relapsed/Refractory Indolent B-Cell Lymphoproliferative Disorders and Mantle Cell Lymphoma (MCL)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of 1 of the following:

- Chronic lymphocytic leukemia (CLL)

- B-cell small lymphocytic leukemia (SLL)

- Any marginal zone lymphoma

- Grade 1-3A follicular lymphoma

- Waldenstrom's macroglobulinemia

- Mantle cell lymphoma

- No transformed indolent lymphoma

- Assessable disease (phase I)

- Measurable disease (phase I and II), defined as ≥ one lesion that can be accurately
measured in ≥ 1 dimension as ≥ 2 cm by conventional techniques OR ≥ 1 cm by spiral CT
scan

- Lymph nodes measuring ≤ 1 cm in the short axis are considered normal

- Relapsed or refractory disease

- Must have received at least 1 prior therapeutic regimen but no more than 3 prior
conventional cytotoxic therapy regimens

- No known brain metastases or meningeal disease

PATIENT CHARACTERISTICS:

- Karnofsky performance status > 50%

- Absolute neutrophil count > 1,000/mcl (more than 500/mcl if known lymphomatous
involvement)

- Platelet count ≥ 50,000/mcl

- Total bilirubin < 1.5 times upper limit of normal (ULN) (less than 5 mg/dL if known
history of Gilbert's disease)

- AST and ALT ≤ 2.5 times ULN (4 times ULN if liver involvement)

- Creatinine < 1.5 times ULN OR creatinine clearance > 50 mL/min

- Patients may have febrile episodes up to 38.5ºC without evidence of active infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No New York Heart Association class III or IV congestive heart failure

- No uncontrolled intercurrent illness, including any of the following:

- Ongoing or active infection

- Cerebrovascular accident or transient ischemic attack within 6 months of study
entry

- Unstable angina pectoris

- Cardiac arrhythmia

- EKG evidence of acute ischemia

- Psychiatric illness/social situations that would limit compliance with study
requirements

- No uncontrolled hypertension requiring active manipulation of antihypertensive
medications

- No known or active HIV infection

- No history of hypersensitivity to bortezomib, boron, or mannitol

- No peripheral neuropathy > grade 2

- No other malignancy within the past 5 years except curatively treated non
life-threatening malignancies, such as cutaneous basal cell or squamous cell
carcinoma or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior therapy

- Prior stem cell transplantation allowed

- Preparative cytoreductive and high-dose therapies considered 1 prior therapy

- At least 4 weeks since prior cytotoxic chemotherapy (6 weeks since prior nitrosoureas
or mitomycin C)

- At least 12 weeks since prior radioimmunotherapy

- One prior course comprising tositumomab or ibritumomab tiuxetan allowed

- At least 1 week since prior palliative steroids for NHL

- No therapeutic monoclonal antibodies (e.g., rituximab, tositumomab, ibritumomab,
alemtuzumab, etc.) within 3 months of study entry

- Patients treated with monoclonal antibodies within 3 months allowed provided
disease progressed on this therapy AND no treatment received 7 days prior to
study entry

- Seven days since prior rituximab (for patients enrolled in phase I portion)

- No major surgery within 4 weeks of study entry

- No other concurrent investigational agents

- No other concurrent anticancer therapy