Bortezomib and Fludarabine With or Without Rituximab in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or 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)