Combination Chemotherapy and Rituximab in Treating Patients With HIV-Associated Stage I, Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma
Combination Chemotherapy and Rituximab in Treating Patients With HIV-Associated Stage I, Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma
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. 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.
PRIMARY OBJECTIVES:

 I. To determine the complete response rate after treatment with EPOCH given either
 concurrently or sequentially with rituximab.

 SECONDARY OBJECTIVES:

 I. To evaluate the toxicity of EPOCH given either concurrently or sequentially with
 rituximab.

 II. To evaluate the effect of EPOCH given either concurrently or sequentially with rituximab
 on immune function (CD4, CD8 lymphocyte count) after two cycles of EPOCH, and 1 month, 3
 months, 6 months, and 12 months after the completion of EPOCH.

 III. To evaluate the effect of EPOCH given either concurrently or sequentially with rituximab
 on HIV and EBV viral load after two cycles of EPOCH, and 1 month, 3 months, 6 months, and 12
 months after the completion of EPOCH.

 IV. To evaluate 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.

 V. To determine whether rituximab or the concurrent use of antiretroviral therapy
 significantly alters the steady state concentration of etoposide, doxorubicin, or vincristine
 during the first cycle of therapy.

 VI. To determine whether steady state concentration of etoposide or doxorubicin correlate
 with nadir neutrophil and platelet count during the first cycle of therapy.

 VII. To determine time to progression and overall survival in patients treated with EPOCH
 given either concurrently or sequentially with rituximab.

 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 intravenously (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.
Inclusion Criteria:

 -  Previously untreated histologically or cytologically documented B-cell non-Hodgkin's
 lymphoma; the following histologies are eligible: diffuse large B-cell lymphoma,
 high-grade large cell immunoblastic lymphoma, anaplastic large cell lymphoma,
 Burkitt's lymphoma, high-grade B-cell lymphoma, Burkitt-like (small non-cleaved
 lymphoma)

 -  Tumors must be CD20 positive

 -  Documented HIV infection: documentation may be serologic (ELISA, western blot),
 culture, or quantitative PCR or bDNA assays

 -  Evaluable or measurable disease

 -  Stage I and IE or Stage II-IV disease patients

 -  ANC >= 1000 cells/mm^3

 -  Platelet count >= 75,000/mm^3 unless cytopenias are secondary to lymphoma

 -  All patients must be off colony stimulating factor therapy at least 24 hours prior to
 chemotherapy

 -  Transaminase =< 5 times the upper limit of normal unless secondary to hepatic
 infiltration with lymphoma or isolated hyperbilirubinemia associated with the use of
 indinavir or other antiretrovirals

 -  Total Bilirubin < 2.0 unless secondary to hepatic infiltration with lymphoma or
 isolated hyperbilirubinemia associated with the use of indinavir or other
 antiretrovirals; for bilirubin > 3.0 due to hepatic involvement the initial dose of
 doxorubicin will be decreased by 50% and the initial dose of vincristine will be
 omitted

 -  Creatinine < 2.0 unless due to lymphoma

 -  KPS >= 50 (ECOG PS 0, 1, or 2)

 -  Able to give consent

 -  Female patients must have a negative pregnancy test within 72 hours of entering into
 the study; males and females must agree to use adequate birth control if conception is
 possible during the study; women must avoid pregnancy and men avoid fathering children
 while in the study

 -  Patients already receiving erythropoeitin or G-CSF are eligible

 -  Patients must have a left ventricular ejection fraction that is at or above the lower
 institutional limits of normal, as assessed by nuclear scan or echocardiogram obtained
 within 12 weeks of registration

 -  Lymphomatous meningitis (patients with a positive CSF cytology are eligible)

 Exclusion Criteria:

 -  Previous chemotherapy or radiotherapy for this lymphoma

 -  Primary Central Nervous System Lymphoma (parenchymal brain or spinal cord tumor)

 -  Acute active HIV-associated opportunistic infection requiring antibiotic treatment;
 patients with mycobacterium avium are not excluded; chronic therapy with potentially
 myelosuppressive agents is allowed provided that entry hematologic criteria are met

 -  Concurrent malignancy (excluding in situ cervical cancer, or non-metastatic
 non-melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy)

 -  Previous therapy with rituximab within 12 months; patients treated with rituximab more
 than 12 months earlier are eligible only if it was given for indications other than
 the treatment of intermediate- or high-grade lymphoma (eg, low-grade lymphoma or ITP)