Bortezomib and Antiviral Therapy Followed By Effusion Drainage, Bevacizumab, and Combination Chemotherapy in Treating Patients With Primary Effusion Lymphoma
|ClinicalTrials.gov Identifier: NCT00217503|
Recruitment Status : Completed
First Posted : September 22, 2005
Last Update Posted : June 20, 2013
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.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Biological: bevacizumab Biological: filgrastim Biological: pegfilgrastim Drug: bortezomib Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: ganciclovir Drug: valganciclovir Drug: zidovudine||Phase 2|
- Determine the complete response rate in patients with previously untreated primary effusion lymphoma treated with effusion drainage and bevacizumab in combination with chemotherapy comprising cyclophosphamide, doxorubicin, and etoposide.
- Determine the overall survival, disease-free survival, and progression-free survival of patients treated with this regimen.
- Determine the toxicity of this regimen in previously treated or untreated patients.
- Determine, preliminarily, the biologic effects of targeted oncolytic virotherapy comprising bortezomib, zidovudine, and valganciclovir in these patients.
OUTLINE: This is a 2-part, pilot study.
Patients who are HIV-positive receive highly-active antiretroviral therapy during study treatment.
- Part 1 (targeted oncolytic virotherapy)*: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8, zidovudine IV over 1 hour twice daily on days 1-10, and oral valganciclovir (or ganciclovir IV) twice daily on days 1-14. One day after completion of zidovudine, patients begin treatment in part 2.
NOTE: *Part 1 treatment may be omitted in patients who are acutely ill with primary effusion lymphoma at study entry AND a 10- to 14-day delay of starting part 2 treatment may pose a hazard to the patient.
- Effusion drainage: Patients undergo effusion drainage prior to each course of bevacizumab* and chemotherapy. The drainage tube may remain in place to allow for continuous drainage of effusion during treatment with bevacizumab* and chemotherapy.
- Bevacizumab* plus cyclophosphamide, doxorubicin, and etoposide (iCDE): Patients receive bevacizumab* IV over 30-90 minutes on days 1 and 6, cyclophosphamide, doxorubicin, and etoposide IV continuously over 96 hours beginning on day 1 and continuing until day 5, and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 6 and continuing until day 19 or until blood counts recover OR pegfilgrastim SC on day 6.
NOTE: *Patients may receive iCDE without bevacizumab if they meet any exclusion criteria for receiving bevacizumab.
Treatment with bevacizumab and iCDE repeats every 21 days for 4-8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses beyond CR.
After completion of study treatment, patients are followed monthly for 6 months, every 2 months for 6 months, every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study within 2.5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Official Title:||Primary Effusion Lymphoma: A Pilot Trial of Bevacizumab and Modified Dose-Adjusted Infusional CDE Chemotherapy Preceded by a Brief Pre-Phase Assessment of Targeted Oncolytic Virotherapy With Bortezomib, Zidovudine and Valganciclovir|
|Study Start Date :||July 2005|
|Study Completion Date :||June 2007|
- Response to therapy as measured by overall, disease-free, and progression-free survival each month
- Effects of high-dose zidovudine and ganciclovir on tumor cells measured by various assays after 2 weeks of study treatment
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00217503
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|Principal Investigator:||Richard F. Little, MD||NCI - HIV and AIDS Malignancy Branch|