RATIONALE: Drugs used in chemotherapy use 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. It is not yet known whether combination chemotherapy is more effective with or without rituximab for non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
recurrent adult diffuse small noncleaved cell/Burkitt's lymphoma recurrent adult diffuse large cell lymphoma	Drug: carboplatin  Drug: etoposide  Drug: filgrastim  Drug: ifosfamide  Drug: rituximab	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the progression-free and overall survival of patients with relapsed or refractory, CD20 expressing, aggressive, B-cell non-Hodgkin's lymphoma treated with ifosfamide, carboplatin, and etoposide with or without rituximab. II. Compare the unconfirmed response rate of patients treated with these regimens. III. Determine the toxicity of ifosfamide, carboplatin, and etoposide with rituximab in these patients.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified according to histology (large B-cell vs other) and risk group (low/low-intermediate vs high-intermediate/high). Patients are randomized to one of two treatment arms. Arm I: Patients receive etoposide IV over 1 hour on days 1-3, carboplatin IV over 1 hour on day 2, ifosfamide IV continuously for 24 hours on day 2, and filgrastim (G-CSF) subcutaneously (SC) on days 5-12. Treatment continues every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive rituximab IV on day 1, etoposide IV over 1 hour on days 2-4, carboplatin IV over 1 hour on day 3, ifosfamide IV continuously for 24 hours on day 3, and G-CSF SC on days 6-13. Patients also receive rituximab IV on day 8 of course 1. Treatment continues every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 376 patients (188 per arm) will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven aggressive B-cell non-Hodgkin's lymphoma that has failed prior combination chemotherapy with an anthracycline-containing regimen; Eligible histologies: Diffuse large cell; Small non-cleaved cell/Burkitt's lymphoma; No lymphoblastic or mantle cell lymphoma
• First relapse or primary refractory disease
• Ineligible for or refused treatment with salvage chemotherapy followed by high-dose therapy and autologous stem cell rescue
• Documented CD20 antigen expression
• Measurable disease
• No clinical evidence of CNS involvement by lymphoma

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics; No prior rituximab
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: Recovered from toxic effects of all prior therapy; No other concurrent therapy unless disease progression occurs

--Patient Characteristics--

• Age: Over 18
• Performance status: Zubrod 0-2
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 2 times upper limit of normal
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min
• Other: HIV negative; Not pregnant or nursing; Fertile patients must use effective contraception; No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36688,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
      CCOP - Greater Phoenix, Phoenix,  Arizona,  85006-2726,  United States
      Veterans Affairs Medical Center - Phoenix (Hayden), Phoenix,  Arizona,  85012,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
      Veterans Affairs Medical Center - Little Rock (McClellan), Little Rock,  Arkansas,  72205,  United States
California
      Cancer Center and Beckman Research Institute, City of Hope, Duarte,  California,  91010-3000,  United States
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Chao Family Comprehensive Cancer Center, Orange,  California,  92868,  United States
      David Grant Medical Center, Travis Air Force Base,  California,  94535,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      University of California Davis Medical Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States
      Veterans Affairs Medical Center - Long Beach, Long Beach,  California,  90822,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80010,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
      Dwight David Eisenhower Army Medical Center, Fort Gordon,  Georgia,  30905-5650,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      Loyola University Medical Center, Maywood,  Illinois,  60153,  United States
      Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital), Hines,  Illinois,  60141,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40511-1093,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71130,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Veterans Affairs Medical Center - Boston (Jamaica Plain), Jamaica Plain,  Massachusetts,  02130,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      CCOP - Grand Rapids Clinical Oncology Program, Grand Rapids,  Michigan,  49503,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Providence Hospital - Southfield, Southfield,  Michigan,  48075-9975,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
Mississippi
      Keesler Medical Center - Keesler AFB, Keesler AFB,  Mississippi,  39534-2576,  United States
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Veterans Affairs Medical Center - Biloxi, Biloxi,  Mississippi,  39531-2410,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110-0250,  United States
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
Ohio
      Barrett Cancer Center, The University Hospital, Cincinnati,  Ohio,  45219,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Kettering,  Ohio,  45429,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428,  United States
Oklahoma
      Oklahoma Medical Research Foundation, Oklahoma City,  Oklahoma,  73104,  United States
      Veterans Affairs Medical Center - Oklahoma City, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      CCOP - Columbia River Program, Portland,  Oregon,  97213,  United States
      Oregon Cancer Center, Portland,  Oregon,  97201-3098,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
      Texas Tech University Health Science Center, Lubbock,  Texas,  79423,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7811,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0209,  United States
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75216,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78284,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States
      Swedish Cancer Institute, Seattle,  Washington,  98104,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States

Study chairs or principal investigators

David G. Maloney,  Study Chair,  Southwest Oncology Group   

Study ID Numbers:  CDR0000068320; SWOG-S0019
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  December 6, 2000
ClinicalTrials.gov Identifier:  NCT00006708
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08