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
18 Years
N/A
Both
Lymphoma
Trial Information
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
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
- Part 2
- 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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Response to therapy as measured by overall, disease-free, and progression-free survival each month
Safety Issue:
No
Principal Investigator
Richard F. Little, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
NCI - HIV and AIDS Malignancy Branch
Authority:
United States: Federal Government
Study ID:
CDR0000441214
NCT ID:
NCT00217503
Start Date:
July 2005
Completion Date:
June 2007
Related Keywords:
- Lymphoma
- AIDS-related peripheral/systemic lymphoma
- Lymphoma
- Lymphoma, Primary Effusion
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda, Maryland 20892-1182 |
