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

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.

Conditions

• Lymphoma

Interventions

BIOLOGICAL

rituximab

375mg/m2 on Day 1

DRUG

bortezomib

Part A: Velcade Day 1 and Day 8 of a 28-day cycle, with inter-subject dose escalation over four dose levels: 0.7 mg/m2, 1 mg/m2, 1.3 mg/m2 and 1.5 mg/m2 Part B: Velcade on Days 1 and 8 of a 21-day cycle.

DRUG

carboplatin

Carboplatin will be dosed to an AUC=5, calculated using the Calvert formula (5 x \[creatinine clearance + 25\]; the maximum dose of carboplatin is 750 mg. Part A: AUC=5 (maximum 750 mg) IV administered on Day 9. Part B: AUC=5 (maximum 750 mg) IV administered on Day 2.

DRUG

dexamethasone

Part A: 20 mg IV on Days 8-10. Part B: 20 mg IV on Days 1-3 and on Day 8.

DRUG

etoposide

Part A: 100 mg/m2 IV Days 8-10. Part B: 100 mg/m2 IV daily on Days 1 to 3.

DRUG

ifosfamide

Part A: 5000 mg/m2 mixed with an equal amount of Mesna as a 24 hour continuous IV infusion on Day 9. Part B: 5000 mg/m2 mixed with an equal dose of Mesna administered via continuous infusion for 24 hours beginning on Day 2.

GENETIC

polymerase chain reaction

Correlate EBV/HHV-8 viral load changes with lymphoma response. HIV and EBV/HHV-8 viral loads will be assessed on baseline, day 2, 4, and 8 of week 1 of Part A.

GENETIC

western blotting

Peripheral blood mononuclear cells will be collected at Day 1 prior to chemotherapy, Day 2, 4 and 8 (prior to chemotherapy) then weekly during Part A, just prior to each additional cycle of Part B and at treatment completion. Western blot using antibody specific for APOBEC3G and antibody against actin for internal control will be used to quantify APOBEC3G levels. Changes at will be compared with baseline using a paired t-test.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• The Emmes Company, LLC

  collaborator INDUSTRY

• AIDS Malignancy Consortium

  lead NETWORK

Principal Investigators

• Erin G. Reid, MD · University of California, San Diego

• William Wachsman, MD · University of California, San Diego

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-11-30

Primary Completion

2014-10-31

Completion

2014-11-30

Countries

• United States

Study Locations