A Phase II, Open-Label Study of Bortezomib (Velcade), Cladribine and Rituximab (VCR) in Advanced, Newly Diagnosed and Relapsed/Refractory Mantle Cell and Indolent Lymphomas

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Biopsy confirmed advanced lymphoma, including any of the following subtypes:

- Mantle cell lymphoma

- Marginal zone lymphoma

- Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia)

- Small lymphocytic lymphoma

- Follicular lymphoma

- Must have received ≥ 1 prior treatment

- Newly diagnosed OR relapsed/refractory disease

- No history of disease refractory to a purine analog, defined as remission
duration of < 6 months with therapy that included fludarabine, pentostatin, or
cladribine

- CD20-positive disease

- Meets ≥ 1 of the following criteria*:

- Symptomatic disease

- Cytopenia related to lymphoma

- Leukemia phase (malignant lymphocytes > 5,000/μL)

- Mass > 5 cm in greatest diameter

- Patients with lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia) must
meet ≥ 1 of the following additional criteria:

- Serum viscosity ≥ 4 cp

- Serum monoclonal protein > 5 g/L

- Concurrent primary systemic AL amyloidosis

- Cold agglutinin disease NOTE: *Patients with mantle cell lymphoma are not
required to meet these criteria.

- No CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

- ANC ≥ 1,000/mm^3 (unless due to bone marrow infiltration with lymphoma)

- Platelet count ≥ 100,000/mm^3(unless due to bone marrow infiltration with lymphoma or
due to autoimmune thrombocytopenia secondary to lymphoma)

- Creatinine normal OR creatinine clearance ≥ 20 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No peripheral neuropathy ≥ grade 2

- None of the following:

- Myocardial infarction within the past 6 months

- NYHA class III-IV heart failure

- Uncontrolled angina

- Severe uncontrolled ventricular arrhythmias

- Evidence of acute ischemia or active conduction system abnormalities by ECG

- Any ECG abnormality at screening has to be documented by the investigator
as not medically relevant

- No hypersensitivity to bortezomib, boron, or mannitol

- No history of intolerance of bortezomib, cladribine, or rituximab

- No serious medical or psychiatric illness likely to interfere with study
participation

- No diagnosis or treatment of another malignancy within the past 3 years except for
completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an
in situ malignancy, or curatively treated prostate cancer deemed to be low-risk

- No known HIV positivity

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Prior bortezomib and/or rituximab allowed

- More than 14 days since prior investigational agents

- No other concurrent investigational agents