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

• Status: Completed
• Trial end date: 2014-11-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy, such as dexamethasone, ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving bortezomib together with combination chemotherapy is more effective with or without rituximab in treating AIDS-related non-Hodgkin lymphoma.

PURPOSE: This clinical trial is studying giving bortezomib together with dexamethasone, ifosfamide, carboplatin, and etoposide to see how well it works with or without rituximab in treating patients with relapsed or refractory AIDS-related non-Hodgkin lymphoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AIDS Malignancy Consortium
• Collaborators: National Cancer Institute (NCI); The Emmes Company, LLC; The EMMES Corporation
• Treatments: BB 1101; Bortezomib; Carboplatin; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Rituximab

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