Bortezomib, Ifosfamide, Carboplatin, and Etoposide, With or Without Rituximab, in Treating Patients With Relapsed or Refractory AIDS-Related Non-Hodgkin Lymphoma

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed relapsed or refractory HIV-associated non-Hodgkin lymphoma (NHL)

  • Must have histologic or cytologic documentation of prior AIDS-associated NHL (i.e., at time of diagnosis) for clinically relapsed and/or refractory disease for which biopsy is not feasible
  • Must have documented HIV seropositivity
  • Must have documentation of Epstein-Barr Virus (EBV)- and/or human herpes virus-8 (HHV-8)- positive infection within the lymphoma (i.e., LMP-1, LANA expression, or positive Epstein-Barr-encoded RNAs [EBERs])

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100%
• Life expectancy > 2 months
• ANC ≥ 1,000/mm³* (growth factor support allowed)
• Hemoglobin ≥ 8.0 g/dL* (growth factor support allowed)
• Platelet count ≥ 100,000/mm³
• Total bilirubin ≤ 1.5 mg/dL
• AST/ALT ≤ 2.5 times institutional upper limit of normal (ULN)
• Serum creatinine ≤ ULN
• Creatinine clearance ≥ 50 mL/min
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception NOTE: *Patients with lymphomatous involvement of the bone unable to meet hematologic criteria are allowed

Exclusion criteria:

• Peripheral neuropathy ≥ grade 2

• Uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection

    • Opportunistic infections controlled by antimicrobial or suppressive therapy allowed, unless the investigator judges the infection likely to become life-threatening in the setting of multi-agent chemotherapy
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • NYHA class III or IV heat failure
  • Myocardial infarction within the past 6 months
  • Uncontrolled angina
  • Severe uncontrolled ventricular or other cardiac arrhythmias
  • Acute ischemia or active conduction system abnormalities by ECG
  • Serious psychiatric or medical illness, that would interfere with study compliance
• Social situations that would interfere with study compliance

• Acute active HIV-associated opportunistic infection requiring antibiotic treatment

  • Mycobacterium avium or candidiasis allowed unless concurrent therapy with moderate-to-strong CYP3A4 inducers or inhibitors is required
  • Chronic myelosuppressive agent therapy allowed provided hematologic criteria are met
• Hypersensitivity to compounds of similar chemical or biological composition to bortezomib, boron, mannitol, ifosfamide, carboplatin, or etoposide
• Concurrent malignancy except carcinoma in situ of the cervix, in situ anal cancer, nonmetastatic nonmelanoma skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy

• Active hepatitis B infection (hepatitis B surface antigen-positive), unless 1 of the following criteria are met:

  • Able to start dual anti-hepatitis B adefovir and telbivudine therapy prior to study
  • Receiving dual anti-hepatitis B therapy for at least 12 weeks prior to study with either agent active against HIV (i.e., entecavir, tenofovir, lamivudine, or emtricitabine)
• Concurrent grapefruit juice/fruit or green tea

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior adverse effects due to agents administered more than 3 weeks earlier
• Glucocorticoid therapy within the past 3 weeks allowed
• More than 3 weeks since prior chemotherapy
• More than 2 weeks since prior radiotherapy
• More than 14 days since prior and no other concurrent investigational agents (other than bortezomib)
• No concurrent moderate-to-strong CYP3A4 inducers or inhibitors other than protease inhibitors
• Concurrent stable (at least 12 weeks) antiretroviral regimen allowed