A Phase I Trial of PS-341 and Fludarabine for Relapsed and Refractory Indolent Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia

Inclusion Criteria:

- Diagnosis of chronic lymphocytic leukemia (CLL) OR indolent non-Hodgkin's lymphoma
(NHL) of any of the following subtypes:

- Follicular lymphoma:

- Grade I follicular small cleaved cell;

- Grade II follicular mixed cell;

- Grade II follicular large cell;

- Diffuse small cleaved cell;

- Small lymphocytic lymphoma;

- Lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia)

- AND

- Extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue
[MALT] lymphoma);

- Nodal marginal zone B-cell lymphoma (monocytoid B-cell lymphoma);

- Splenic marginal zone lymphoma (splenic lymphoma with villous lymphocytes);

- Mantle cell lymphoma:

- No blastic phase mantle cell lymphoma

- Relapsed or refractory, progressive disease:

- First, second, or third relapse

- Measurable disease, meeting 1 of the following criteria:

- At least 1 unidimensionally measurable lesion at least 20 mm by conventional
techniques OR at least 10 mm by spiral CT scan (for NHL patients);

- OR:

- Lymphocytosis > 50,000/mm3 OR evidence of progressive bone marrow infiltration
failure (e.g., hemoglobin 10 g/dL) OR thrombocytopenia (i.e., platelet count <
100,000/mm3) with > 30% infiltration of bone marrow by leukemia (for CLL
patients)

- No measurable lymphadenopathy (for CLL and Waldenstrom's macroglobulinemia patients)

- No evidence of CNS lymphoma

- Performance status:

- ECOG 0-2

- Life expectancy:

- More than 12 weeks

- No history of uncontrolled orthostatic hypotension

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No uncontrolled concurrent illness

- No grade 2 or greater neuropathy

- No history of allergy or anaphylaxis to mannitol, bortezomib, fludarabine, or boron

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- At least 4 weeks since prior monoclonal antibody (MoAB) therapy:

- Patients who have received MoAB therapy within the past 3 months must have
documented disease progression since receiving this therapy

- No prior allogeneic stem cell transplantation

- More than 4 weeks since prior chemotherapy

- Prior fludarabine allowed

- At least 1 week since prior steroids

- At least 3 months since prior radio-immunotherapy

- More than 4 weeks since prior radiotherapy

- No prior bortezomib

- Absolute neutrophil count at least 1,500/mm3

- Platelet count at least 75,000/mm3 (greater than 50,000/mm3 if lymphomatous bone
marrow involvement is present)

- Bilirubin no greater than 2.0 mg/dL

- AST/ALT no greater than 4 times normal

- Creatinine clearance greater than 40 mL/min

- No other concurrent investigational agents or treatments for the malignancy

- No brain metastases

- OR:

Quantitation of IgM paraprotein (for Waldenstrom's macroglobulinemia patients)