Bortezomib and Antiviral Therapy Followed By Effusion Drainage, Bevacizumab, and Combination Chemotherapy in Treating Patients With Primary Effusion Lymphoma

NCT00217503 | Completed Phase 2

• 3 other identifiers: CDR0000441214NCI-05-C-0203NCI-P6330
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Herpesvirus is found in the cancer cells of patients with primary effusion lymphoma. Antiviral drugs, such as zidovudine and valganciclovir, may be able to act against the herpesvirus in the cancer cells to help kill the cancer cells. Bortezomib may help the antiviral drugs kill the cancer cells. Draining the effusion removes fluid that has built up. Monoclonal antibodies, such as bevacizumab, 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. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with antiviral therapy followed by effusion drainage, bevacizumab, and combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with antiviral therapy followed by effusion drainage, bevacizumab, and combination chemotherapy works in treating patients with primary effusion lymphoma.

Conditions

Lymphoma

Keywords

AIDS-related peripheral/systemic lymphoma

Outcome Measures

Primary Outcomes (1)

• Response to therapy as measured by overall, disease-free, and progression-free survival each month

Secondary Outcomes (1)

• Effects of high-dose zidovudine and ganciclovir on tumor cells measured by various assays after 2 weeks of study treatment

Interventions

bevacizumab BIOLOGICAL

filgrastim BIOLOGICAL

pegfilgrastim BIOLOGICAL

bortezomib DRUG

cyclophosphamide DRUG

doxorubicin hydrochloride DRUG

etoposide DRUG

ganciclovir DRUG

valganciclovir DRUG

zidovudine DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed primary effusion lymphoma (PEL) involving a body cavity * Kaposi's sarcoma associated-herpesvirus * Any anatomic site or distribution of involvement allowed * HIV infection allowed * Previously treated or untreated disease * No mass lesions in the brain (for patients receiving bevacizumab during study treatment) PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-3\* NOTE: \*ECOG 4 allowed if due to a mechanical effect of the PEL that can be corrected by effusion drainage resulting in improved performance status to ECOG 3 or better Life expectancy * Not specified Hematopoietic * Absolute neutrophil count \> 1,000/mm\^3 * Platelet count \> 75,000/mm\^3 * No active bleeding or coagulopathy (for patients receiving bevacizumab during study treatment) Hepatic * AST and ALT \< 3 times upper limit of normal (ULN) (6 times ULN if due to hyperalimentation) * Bilirubin \< 2.0 mg/dL OR * Total bilirubin ≤ 4.5 mg/dL AND direct bilirubin \< 0.4 mg/dL (for patients with Gilbert's syndrome or receiving protease-inhibitor therapy) Renal * Creatinine ≤ 1.5 mg/dL OR * Creatinine clearance \> 50 mL/min Cardiovascular * Patients receiving bevacizumab during study treatment must meet the following criteria: * No deep venous or arterial thrombosis within the past 6 months * No uncontrolled hypertension (i.e., systolic blood pressure \[BP\] \> 160 mm Hg or diastolic BP \> 95 mm Hg) * No unstable angina * No New York Heart Association class II-IV congestive heart failure * No cardiac arrhythmia requiring medication * No clinically significant peripheral artery disease * No peripheral vascular disease ≥ grade 2 * No prior myocardial infarction * No transient ischemic attack or cerebral vascular accident within the past 6 months * No other clinically significant cardiovascular disease Neurologic * Patients receiving bevacizumab during study treatment must meet the following criteria: * No uncontrolled seizure disorder * No CNS bleeding within the past 6 months * No other substantial CNS disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other malignancy requiring treatment that would preclude study treatment, including, but not limited to, any of the following: * Life-threatening Kaposi's sarcoma * Non-resectable lung cancer * Acute leukemia * No grade IV organ dysfunction unrelated to PEL * No infection requiring chronic systemic therapy that would preclude study treatment (except HIV, hepatitis B, or hepatitis C), including, but not limited to, any of the following: * Invasive aspergillosis * End-organ cytomegalovirus (CMV) * CMV retinitis (e.g., ocular implants not requiring systemic therapy) allowed if controlled with local therapy * No other condition or circumstance that would preclude study participation * No gastrointestinal bleeding within the past 6 months (for patients receiving bevacizumab during study treatment) * No pathological condition that would confer a high risk for bleeding (for patients receiving bevacizumab during study treatment) PRIOR CONCURRENT THERAPY: Biologic therapy * No live virus vaccines (e.g., vaccinia or rotavirus) or bacterial vaccines during and for 3 months after completion of study treatment Chemotherapy * No prior cumulative anthracycline dose \> 450 mg/m\^2 (unless cardiac ejection fraction normal) Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified Other * No concurrent chronic daily aspirin ≥ 325 mg/day or nonsteroidal medication that interferes with platelet function (for patients receiving bevacizumab during study treatment) * No concurrent therapeutic anticoagulation (INR \> 1.5) unless patient is on full-dose warfarin (for patients receiving bevacizumab during study treatment) * Full-dose anticoagulants allowed provided both of the following criteria are met: * INR normal * On a stable dose of warfarin or low-molecular weight heparin

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

Bevacizumab; Filgrastim; pegfilgrastim; Bortezomib; Cyclophosphamide; Doxorubicin; Etoposide; Ganciclovir; Valganciclovir; Zidovudine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Richard F. Little, MD

  NCI - HIV and AIDS Malignancy Branch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 20, 2005
• First Posted: September 22, 2005
• Study Start: July 1, 2005
• Study Completion: June 1, 2007
• Last Updated: June 20, 2013

Record last verified: 2007-04

Locations

US (1)