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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Lymphoma

Thank you

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 OfficeBethesda, Maryland  20892-1182