Bortezomib, Rituximab, Cyclophosphamide, and Prednisone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

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