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