Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma

OBJECTIVES:

Primary

- Determine the complete response rate (complete response and complete response
unconfirmed) in patients with newly diagnosed, AIDS-related B-cell non-Hodgkin's
lymphoma treated with doxorubicin hydrochloride liposome, rituximab, cyclophosphamide,
vincristine, and prednisone (DR-COP).

- Determine the duration of response (relapse-free survival) in patients treated with this
regimen.

- Determine the median survival time of patients treated with this regimen.

- Determine rate of bacterial, fungal, and opportunistic infections in patients treated
with this regimen.

Secondary

- Determine, preliminarily, the relationship between MDR-1 expression in tumor tissue and
response to therapy in patients treated with this regimen.

- Determine, preliminarily, any relationship between response and survival and BCL-2
expression in tumor tissue in patients treated with this regimen.

- Determine any relationship between development of bacterial, fungal, and/or
opportunistic infections and baseline CD4 lymphocyte count, HIV-1 RNA level, and
quantitative immunoglobulin levels, or changes in quantitative immunoglobulin levels
over time in patients treated with this regimen.

- Compare the results of positron emission tomography (PET) scanning with traditional CT
scans in predicting response to therapy in these patients.

- Examine the relationship between chemotherapeutic drug levels and receipt of specific
antiretroviral and/or anti-infective medications in these patients.

- Examine the mortality and the causes of death in patients treated with this regimen.

- Determine event-free survival at 1 year.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive doxorubicin hydrochloride liposome IV over 90 minutes, rituximab IV over 5-7
hours, cyclophosphamide IV over 1 hour, and vincristine IV over 1-2 minutes on day 1 and oral
prednisone on days 1-5. Patients also receive filgrastim (G-CSF), sargramostim (GM-CSF), or
pegfilgrastim beginning on day 3 and continuing until blood counts recover. Treatment repeats
every 21-28 days for up to 8 courses in the absence of disease progression or unacceptable
toxicity.

Patients undergo laboratory/biomarker studies at baseline and after every 2 courses of
chemotherapy. Tissue is examined by immunohistochemistry for BCL-2, Ki67, and MDR-1, along
with other markers.

After completion of study treatment, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed AIDS-related B-cell non-Hodgkin's lymphoma
(NHL), including any of the following subtypes:

- Grade III follicular large cell lymphoma

- Diffuse large B-cell lymphoma

- Immunoblastic lymphoma

- Plasmablastic lymphoma

- Primary effusion lymphoma

- Previously untreated disease

- Any stage disease

- CD20 positive disease

- Must have documented HIV infection

- Documentation may be by serology (enzyme-linked immunosorbent assay, western
blot), culture, or quantitative polymerase chain reaction or branched DNA assays

- Prior documentation of HIV seropositivity allowed

- Measurable or nonmeasurable disease

- Currently receiving effective highly active anti-retroviral therapy

- No primary CNS lymphoma, including parenchymal brain or spinal cord lymphoma

- No presence of leptomeningeal disease (positive cerebrospinal fluid for lymphoma) or
presence of metastatic disease to brain, in terms of any mass lesion

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100%

- Life expectancy ≥ 2 months

- Absolute granulocyte (neutrophil) count ≥ 1,000/mm³ (unless secondary to lymphomatous
involvement of bone marrow)

- Platelet count ≥ 75,000/mm³ (unless secondary to lymphomatous involvement of bone
marrow or due to HIV-related thrombocytopenia)

- Bilirubin ≤ 2.0 mg/dL (unless elevated secondary to lymphomatous involvement of liver
or biliary system or due to other HIV medications [e.g., indinavir, tenofavir, or
atazanavir])

- SGOT ≤ 5 times upper limit of normal

- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min (unless secondary to renal
involvement by lymphoma)

- LVEF normal by MUGA or echocardiogram

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment

- No other malignancy, except nonmelanoma skin cancer, carcinoma in situ of the cervix,
or Kaposi's sarcoma that does not require systemic therapy

- No serious, ongoing, nonmalignant disease or infection that would preclude study
compliance, in the opinion of the investigator

- No history of cutaneous or mucocutaneous reactions, or diseases in the past, due to
any cause, severe enough to cause hospitalization or an inability to eat or drink for
≥ 2 days

- No acute, intercurrent infection that would preclude study treatment

- Patients with Mycobacterium avium are eligible

- No cardiovascular problems, including any of the following:

- Myocardial infarction within the past 6 months

- New York Heart Association class II-IV heart failure

- Uncontrolled angina

- Severe uncontrolled ventricular arrhythmias

- Clinically significant pericardial disease

- ECG evidence of acute ischemic or active conduction system abnormalities.

- No shortness of breath at rest

- Arterial PO_2 ≥ 70 or pulse oximeter-derived O_2 saturation ≥ 94% on room air (unless
due to lymphomatous involvement of the lungs)

- Able to comply with study and provide adequate informed consent

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 4 weeks since prior major surgery (except diagnostic surgery)

- At least 12 months since prior rituximab unless it was only given for indications
other than the treatment of aggressive lymphoma

- No prior cytotoxic chemotherapy or radiotherapy for this lymphoma

- Concurrent radiotherapy, with or without steroids, for emergency conditions
secondary to lymphoma (i.e., CNS tumor or cord compression) allowed

- No zidovudine or zidovudine-containing regimen (including Combivir® or Trizivir®)
during and for 2 months after completion of chemotherapy

- Concurrent erythropoietin or filgrastim (G-CSF) allowed

- Growth factor therapy must be discontinued ≥ 24 hours prior to study entry