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Bortezomib, Ifosfamide, Carboplatin, and Etoposide, With or Without Rituximab, in Treating Patients With Relapsed or Refractory AIDS-Related Non-Hodgkin Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), December 2008
First Received: January 9, 2008   Last Updated: April 24, 2009   History of Changes
Sponsors and Collaborators: AIDS Associated Malignancies Clinical Trials Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00598169
  Purpose

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.


Condition Intervention
Lymphoma
Biological: rituximab
Drug: bortezomib
Drug: carboplatin
Drug: dexamethasone
Drug: etoposide
Drug: ifosfamide
Genetic: polymerase chain reaction
Genetic: western blotting
Other: questionnaire administration

MedlinePlus related topics: Cancer Kaposi's Sarcoma Lymphoma
Drug Information available for: Dexamethasone Etoposide Carboplatin Dexamethasone acetate Doxiproct plus Etoposide phosphate Rituximab Bortezomib Dexamethasone Sodium Phosphate Ifosfamide
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of bortezomib [ Designated as safety issue: Yes ]
  • Overall lymphoma response rate [ Designated as safety issue: No ]
  • Effects on HIV and Epstein-Barr virus (EBV)/human herpes virus (HHV)-8 viral loads [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median overall survival at 1 year [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTC v3.0 [ Designated as safety issue: Yes ]
  • Impact of bortezomib alone and in combination with rituximab, ifosfamide, carboplatin, and etoposide ([R]ICE) on serum HIV viral loads and APOBEC3G levels [ Designated as safety issue: No ]
  • Impact of bortezomib alone and in combination with (R)ICE on EBV and HHV-8 lytic activation using serum viral loads [ Designated as safety issue: No ]
  • Safety of bortezomib alone in patients with relapsed or refractory AIDS-associated lymphomas [ Designated as safety issue: Yes ]
  • Correlation of EBV/HHV-8 viral load changes with lymphoma response [ Designated as safety issue: No ]
  • Comparison of above outcomes to a parallel protocol employing ICE +/- rituximab in patients with EBV/HHV-8-negative AIDS-NHL to assess whether bortezomib has additional effects beyond (R)ICE alone [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: November 2007
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00598169

Locations
United States, California
Rebecca and John Moores UCSD Cancer Center Recruiting
La Jolla, California, United States, 92093-0658
Contact: Clinical Trials Office - Rebecca and John Moores UCSD Cancer     858-822-5354     cancercto@ucsd.edu    
Sponsors and Collaborators
AIDS Associated Malignancies Clinical Trials Consortium
Investigators
Study Chair: Erin G. Reid, MD University of California, San Diego
Investigator: William Wachsman, MD University of California, San Diego
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000581078, AMC-053
Study First Received: January 9, 2008
Last Updated: April 24, 2009
ClinicalTrials.gov Identifier: NCT00598169     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
AIDS-related diffuse large cell lymphoma
AIDS-related diffuse mixed cell lymphoma
AIDS-related diffuse small cleaved cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related lymphoblastic lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
AIDS-related small noncleaved cell lymphoma

Study placed in the following topic categories:
Anti-Inflammatory Agents
Dexamethasone
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Central Nervous System Lymphoma, Primary
Hormones
Lymphoblastic Lymphoma
Etoposide phosphate
Lymphoma, Large-cell, Immunoblastic
Kaposi Sarcoma
Lymphoma, Small Cleaved-cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Large-cell
Alkylating Agents
Lymphoma
Etoposide
Dexamethasone acetate
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Rituximab
Sarcoma, Kaposi
Bortezomib
Carboplatin
Small Non-cleaved Cell Lymphoma
Glucocorticoids
Protease Inhibitors
Lymphatic Diseases

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Dexamethasone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Therapeutic Uses
Alkylating Agents
Etoposide
Lymphoma
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Rituximab
Bortezomib
Gastrointestinal Agents
Enzyme Inhibitors
Carboplatin
Glucocorticoids
Pharmacologic Actions
Protease Inhibitors
Lymphatic Diseases
Neoplasms
Ifosfamide
Autonomic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on May 07, 2009