RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with HIV-associated stage I, stage II, stage III, or stage IV non-Hodgkin's lymphoma.

OBJECTIVES:

• Compare the complete response rate of patients with intermediate- or high-grade HIV-associated stage I, I_E, II, III, or IV B-cell non-Hodgkin's lymphoma treated with etoposide, doxorubicin, vincristine, prednisone, and cyclophosphamide with concurrent versus sequential rituximab.
• Compare the toxicity of these regimens in these patients.
• Compare time to progression and overall survival of patients treated with these regimens.
• Compare the effect of these regimens on immune function (CD4 and CD8 lymphocyte count) in these patients.
• Compare the effect of these regimens on HIV and Epstein-Barr virus (EBV) viral load in these patients.
• Determine the relationship between EBV viral load and EBV CD8 cytotoxic T cells in the peripheral blood and the presence of EBV in lymphoma tumor cells in patients treated with these regimens.
• Determine whether rituximab or the concurrent use of antiretroviral therapy significantly alters the steady state concentration of etoposide, doxorubicin, or vincristine in these patients.
• Determine whether steady state concentrations of etoposide and doxorubicin correlate with nadir neutrophil and platelet count in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to CD4 count (less than 100/mm^3 vs at least 100/mm^3), age-adjusted International Prognostic Index adverse risk factors (0 or 1 vs 2 or 3), and concurrent antiretroviral therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive rituximab IV over 2-4 hours prior to each course of chemotherapy. Treatment repeats every 3 weeks for 4-6 courses. Patients who achieve a complete response after 4 courses of chemotherapy and rituximab receive additional rituximab alone weekly for 2 weeks.
• Arm II: Patients do not receive rituximab concurrently with chemotherapy. Beginning 4 weeks after completion of chemotherapy, patients receive rituximab IV over 2-4 hours weekly for 6 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 70 patients (35 per treatment arm) will be accrued for this study within 1 year.

• Experimental: Patients receive rituximab IV over 2-4 hours prior to each course of chemotherapy. Treatment repeats every 3 weeks for 4-6 courses. Patients who achieve a complete response after 4 courses of chemotherapy and rituximab receive additional rituximab alone weekly for 2 weeks.
• Experimental: Patients do not receive rituximab concurrently with chemotherapy. Beginning 4 weeks after completion of chemotherapy, patients receive rituximab IV over 2-4 hours weekly for 6 weeks.

DISEASE CHARACTERISTICS:

• Documented HIV infection by serologic, culture, or quantitative assays

• Histologically or cytologically confirmed B-cell non-Hodgkin's lymphoma (NHL) of any of the following histological subtypes:

  • Diffuse large B-cell lymphoma
  • High-grade immunoblastic large cell lymphoma
  • Anaplastic large cell lymphoma
  • Burkitt's lymphoma
  • High-grade B-cell lymphoma
  • Burkitt-like (small noncleaved cell) lymphoma
• Stage I, I_E, II, III, or IV disease
• Previously untreated
• CD20-positive disease
• Measurable or evaluable disease

• No primary CNS lymphoma (parenchymal brain or spinal cord tumor)

  • Patients with lymphamatous meningitis (positive CSF cytology) are eligible NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 50-100% OR
• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3*
• Platelet count ≥ 75,000/mm^3* NOTE: * Unless secondary to lymphoma

Hepatic

• Bilirubin < 2.0 mg/dL*
• AST/ALT ≤ 5 times upper limit of normal* NOTE: * Unless secondary to hepatic infiltration with lymphoma or isolated hyperbilirubinemia associated with the use of indinavir or other antiretrovirals

Renal

• Creatinine < 2.0 mg/dL (unless due to lymphoma)

Cardiovascular

• LVEF normal by nuclear scan or echocardiogram

Other

• Concurrent Mycobacterium avium infection allowed
• No acute active HIV-associated opportunistic infection requiring antibiotics
• No other concurrent malignancy except carcinoma in situ of the cervix, nonmetastatic nonmelanoma skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 24 hours since prior colony-stimulating factors
• No prior rituximab for intermediate- or high-grade lymphoma
• More than 12 months since prior rituximab for other indications (e.g., low-grade lymphoma or idiopathic thrombocytopenic purpura)
• Concurrent filgrastim (G-CSF) or epoetin alfa allowed

Chemotherapy

• No prior chemotherapy for NHL

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for NHL

Surgery

• Not specified

Other

• Concurrent chronic therapy with potentially myelosuppressive agents allowed provided entry hematologic criteria are met

• National Cancer Institute (NCI)
• Eastern Cooperative Oncology Group