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.

Condition	Treatment or Intervention	Phase
AIDS-related diffuse large cell lymphoma AIDS-related immunoblastic large cell lymphoma AIDS-related peripheral/systemic lymphoma AIDS-related small noncleaved cell lymphoma	Drug: cyclophosphamide  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: pegfilgrastim  Drug: prednisone  Drug: rituximab  Drug: vincristine  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

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 etoposide IV continuously, doxorubicin IV continuously, and vincristine IV continuously on days 1-4; oral prednisone on days 1-5; and cyclophosphamide IV over 1 hour on day 5. Patients also receive rituximab IV over 2-4 hours prior to each course of chemotherapy. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously (SC) once daily until blood counts recover or pegfilgrastim SC once approximately 24 hours after the completion of each course of chemotherapy. Treatment repeats every 3 weeks for 4-6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response after 4 courses of chemotherapy and rituximab receive additional rituximab alone weekly for 2 weeks.
• Arm II: Patients receive etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide, and G-CSF as in arm I. Treatment repeats every 3 weeks for 4-6 courses in the absence of disease progression or unacceptable toxicity. 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5216,  United States; Recruiting
      Veterans Affairs Medical Center - Palo Alto, Palo Alto,  California,  94304-1290,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612-9497,  United States; Recruiting
      Veterans Affairs Medical Center - Gainesville, Gainesville,  Florida,  32608-1197,  United States; Recruiting
      Veterans Affairs Medical Center - Miami, Miami,  Florida,  33125,  United States; Recruiting
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States; Recruiting
Georgia
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States; Recruiting
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States; Recruiting
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611-4494,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States; Recruiting
Iowa
      Burgess Health Center, Onawa,  Iowa,  51040,  United States; Recruiting
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      John Stoddard Cancer Center at Iowa Lutheran Hospital, Des Moines,  Iowa,  50316-2301,  United States; Recruiting
      John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States; Recruiting
      Mercy Cancer Center at Mercy Medical Center - Des Moines, Des Moines,  Iowa,  50314,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States; Recruiting
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States; Recruiting
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
      Cancer Center at Tufts - New England Medical Center, Boston,  Massachusetts,  02111,  United States; Recruiting
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States; Recruiting
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007-3731,  United States; Recruiting
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States; Recruiting
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417-2399,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
      Midlands Cancer Center at Midlands Community Hospital, Papillion,  Nebraska,  68128-4157,  United States; Recruiting
      Veterans Affairs Medical Center - Omaha, Omaha,  Nebraska,  68105,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Hampshire
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick,  New Jersey,  08903,  United States; Recruiting
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States; Recruiting
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018,  United States; Recruiting
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States; Recruiting
New York
      Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx,  New York,  10461,  United States; Recruiting
      MBCCOP-Our Lady of Mercy Cancer Center, Bronx,  New York,  10466,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
      Veterans Affairs Medical Center - Brooklyn, Brooklyn,  New York,  11209,  United States; Recruiting
      Veterans Affairs Medical Center - New York, New York,  New York,  10010,  United States; Recruiting
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States; Recruiting
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States; Recruiting
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States; Recruiting
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
      MetroHealth's Cancer Care Center at MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States; Recruiting
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States; Recruiting
Pennsylvania
      Abramson Cancer Center of the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States; Recruiting
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States; Recruiting
      Hahnemann University Hospital, Philadelphia,  Pennsylvania,  19102-1192,  United States; Recruiting
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15236,  United States; Recruiting
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States; Recruiting
      Veterans Affairs Medical Center - Pittsburgh, Pittsburgh,  Pennsylvania,  15240,  United States; Recruiting
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6307,  United States; Recruiting
      Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville,  Tennessee,  37212-2637,  United States; Recruiting
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States; Recruiting
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226-3596,  United States; Recruiting
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States; Recruiting
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States; Recruiting
      Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee,  Wisconsin,  53295,  United States; Recruiting
Australia, New South Wales
      Westmead Hospital, Westmead,  New South Wales,  2145,  Australia; Recruiting
Peru
      Instituto de Enfermedades Neoplasicas, Lima,  34,  Peru; Recruiting
Puerto Rico
      MBCCOP - San Juan, San Juan,  00921-3201,  Puerto Rico; Recruiting
      San Juan City Hospital, San Juan,  00936-7344,  Puerto Rico; Recruiting
      Veterans Affairs Medical Center - San Juan, San Juan,  00927-5800,  Puerto Rico; Recruiting
South Africa
      Pretoria Academic Hospital, Pretoria,  0001,  South Africa; Recruiting

Study chairs or principal investigators

Lawrence D. Kaplan, MD,  San Francisco General Hospital Medical Center   
Joseph A. Sparano, MD,  Study Chair,  Albert Einstein Cancer Research Center   
Yelena Novik, MD,  Study Chair,  New York University School of Medicine   

Study ID Numbers:  CDR0000257660; AMC-034; ECOG-AMC34; NCT00049036
Record last reviewed:  December 2004
Last Updated:  April 5, 2005
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049036
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08