Safety and Efficacy Pilot Trial of the Anti-Viral and Anti-Tumor Activity of Velcade Combined With (R)ICE in Subjects With EBV and/or HHV-8 Positive Relapsed/Refractory AIDS-Associated Non-Hodgkin's Lymphoma

Inclusion Criteria

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