Lymphoma Clinical Trial
Official title:
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
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.
OBJECTIVES:
Primary
- Evaluate the safety and overall lymphoma response rate of bortezomib in combination with
ifosfamide, carboplatin, and etoposide (ICE) with or without rituximab in patients with
Epstein-Barr Virus (EBV)- and/or human herpes virus-8 (HHV-8)- positive relapsed or
refractory HIV-associated non-Hodgkin lymphoma (NHL).
Secondary
- Evaluate the impact of bortezomib alone and in combination with rituximab) and ICE ([R]
ICE) on serum HIV viral loads and APOBEC3G levels.
- Estimate the impact of bortezomib alone and in combination with (R)ICE on EBV and HHV-8
lytic activation using serum viral loads.
- Estimate the median response duration and 1 year overall survival rate of patients
treated with this regimen.
- Evaluate the safety of bortezomib alone in patients with relapsed or refractory
AIDS-associated lymphomas.
- Correlate EBV/HHV-8 viral load changes with lymphoma response.
- Compare the above outcomes to a parallel protocol employing ICE with or without
rituximab in patients with EBV/HHV-8-negative AIDS-NHL to assess whether bortezomib has
additional effects beyond (R)ICE alone.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Patients are assigned to
1 of 2 treatment groups.
- CD20-negative patients
- Part A: Patients receive bortezomib IV over 3-5 seconds on days 1 and 8,
dexamethasone IV and etoposide IV over 2 hours on days 8-10, and ifosfamide IV
continuously over 24-hours and carboplatin IV over 2 hours on day 9. Treatment
repeats every 28 days until the maximum tolerated dose (MTD) is determined.
Patients who tolerate the MTD of bortezomib may move on to part B.
- Part B: Patients receive bortezomib IV over 3-5 seconds at the MTD on days 1 and 8,
dexamethasone IV on days 1-3 and 8, etoposide IV over 2 hours on days 1-3, and
ifosfamide IV continuously over 24-hours and carboplatin IV over 2 hours on day 2.
Treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Some patients may undergo hematopoietic stem
cell transplantation (HSCT).
- CD20-positive patients
- Part A: Patients receive bortezomib, dexamethasone, etoposide, ifosfamide, and
carboplatin as in the CD20-negative patients part A group.
- Part B: Patients receive rituximab IV on day 1. Patients also receive bortezomib,
dexamethasone, etoposide, ifosfamide, and carboplatin as in the CD20-negative
patients part B group. Some patients may undergo HSCT.
Patients undergo blood sample collection periodically for correlative studies. Samples are
analyzed for the effects of bortezomib on viral activation and replication via Taqman
polymerase chain reaction (PCR), and for quantification of APOBEC3G levels via western blot.
Similar studies are performed on the BCLB-1 EBV containing lines, as well as Daudi and other
EBV-transformed B-lymphocyte lines via quantitative viral DNA PCR.
Patients complete the Functional Assessment of Cancer Therapy/GOG-Neurotoxicity
Questionnaire, v4.0 at day 8 and week 4 of Part A and at least once per course of Part B for
assessment of neuropathic pain and/or peripheral neuropathy.
After completion of study treatment, patients achieving complete response (CR) are followed
at 2-4 weeks and then every 3 months for 1 year. Patients not achieving CR at completion of
study treatment and declining further antineoplastic treatment are followed at 2-4 weeks and
then every 3 months for 1 year.
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