RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies, such as rituximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether stem cell transplantation is more effective with or without rituximab in treating relapsed or progressive B-cell diffuse large cell lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of stem cell transplantation with or without rituximab in treating patients who have relapsed or progressive B-cell diffuse large cell lymphoma.

Condition	Treatment or Intervention	Phase
recurrent adult diffuse large cell lymphoma	Drug: carmustine  Drug: cyclophosphamide  Drug: etoposide  Drug: filgrastim  Drug: rituximab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: monoclonal antibody therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare disease-free survival of patients with relapsed or progressive B-cell diffuse large cell lymphoma undergoing stem cell transplantation with or without rituximab.
• Evaluate the effect of rituximab, administered pre-transplant and post-transplant, on the procedure-related mortality of these patients.
• Determine the potential infectious complications of the addition of this drug to autologous stem cell transplantation in these patients.
• Compare overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to relapse (relapsed more than 6 months after either initial complete remission [CR] or CR with positive positron emission tomography or MRI [gallium] vs failed to achieve initial CR or relapsed within 6 months after either initial CR or CR with positive PET or MRI [gallium]) and prior rituximab (yes vs no). Patients are randomized to one of two treatment arms.

Stem cell mobilization

• Arm I: Patients receive rituximab IV over 4-8 hours on days 1, 5, 8, and 13. Patients also receive cyclophosphamide IV over 2 hours on day 9 and filgrastim (G-CSF) subcutaneously (SC) beginning on day 10 and continuing until the last day of apheresis. Stem cells are collected over 1-3 days. Patients also receive rituximab IV over 4-8 hours on days 45 and 52 post-transplant.
• Arm II: Patients receive cyclophosphamide IV over 2 hours on day 1 and G-CSF SC beginning on day 2 and continuing until the last day of apheresis. Stem cells are collected over 1-3 days.

Preparative regimen

• Regimen A (patients who have received prior radiotherapy or are ≥ 61 years of age): Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2.
• Regimen B (all other patients): Patients undergo total body irradiation twice daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Stem cells are reinfused on day 0. Patients receive G-CSF SC beginning on day 6 and continuing until blood counts recover.

Patients are followed for 10 years.

PROJECTED ACCRUAL: A total of 427 patients will be accrued for this study within 3.5 years.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of diffuse large cell lymphoma and meeting the following criteria:
• B-cell type with expression of CD20 either at diagnosis or at relapse
• Relapse after having achieved an initial complete remission (CR) or failure to achieve initial CR (residual radiographic abnormalities after primary therapy allowed if these abnormalities are also positive by positron emission tomography or MRI [gallium])
• No newly diagnosed disease
• No progressive or stable disease to most recent salvage therapy

PATIENT CHARACTERISTICS: Age

• 18 to 70

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• AST or ALT < 3 times upper limit of normal

Renal

• Creatinine ≤ 2.0 mg/dL OR
• Creatinine clearance ≥ 40 mL/min

Cardiovascular

• Cardiac ejection fraction ≥ 40%

Pulmonary

• DLCO ≥ 60% of predicted

Other

• No other malignancy within the past 2 years except basal cell skin cancer or carcinoma in situ of the cervix
• No active infection requiring oral or IV antibiotics
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Chemotherapy
• No more than 3 prior immunotherapy regimens
• At least 3 months since prior rituximab therapy (patients must have responded to the rituximab or the treatments including rituximab)

Chemotherapy

• No more than 3 prior chemotherapy regimens
• Addition of radiation or a monoclonal antibody to chemotherapy is considered one treatment regimen if the addition was part of the initial treatment plan
• Addition of these therapies due to lack of response or poor response would be considered an additional treatment regimen whether given in front-line or salvage setting

Endocrine therapy

• Not specified

Radiotherapy

• See Chemotherapy
• No more than 3 prior radiotherapy regimens
• No prior radioimmunotherapy

Surgery

• Not specified

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
California
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5216,  United States; Recruiting
Colorado
      Boulder Community Hospital, Boulder,  Colorado,  80301-9019,  United States; Recruiting
      CCOP - Colorado Cancer Research Program, Incorporated, Denver,  Colorado,  80224,  United States; Recruiting
      Hope Cancer Care Center at Longmont United Hospital, Longmont,  Colorado,  80501,  United States; Recruiting
      Medical Center of Aurora - South Campus, Aurora,  Colorado,  80012-0000,  United States; Recruiting
      Penrose Cancer Center at Penrose Hospital, Colorado Springs,  Colorado,  80933,  United States; Recruiting
      Porter Adventist Hospital, Denver,  Colorado,  80210,  United States; Recruiting
      Presbyterian - St. Luke's Medical Center, Denver,  Colorado,  80218,  United States; Recruiting
      Rocky Mountain Cancer Centers - Denver Rose, Denver,  Colorado,  80220,  United States; Recruiting
      Rocky Mountain Cancer Centers - Thornton, Thornton,  Colorado,  80229,  United States; Recruiting
      Sky Ridge Medical Center, Lone Tree,  Colorado,  80124,  United States; Recruiting
      St. Joseph Hospital, Denver,  Colorado,  80218-1191,  United States; Recruiting
      St. Mary-Corwin Regional Medical Center, Pueblo,  Colorado,  81004,  United States; Recruiting
      Swedish Medical Center, Englewood,  Colorado,  80112,  United States; Recruiting
Florida
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612-9497,  United States; Recruiting
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Illinois
      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
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
Iowa
      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
Louisiana
      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
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Nebraska
      Midlands Cancer Center at Midlands Community Hospital, Papillion,  Nebraska,  68128-4157,  United States; Recruiting
New Jersey
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  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
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
Ohio
      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
Pennsylvania
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  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
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
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  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
Australia, New South Wales
      Westmead Hospital, Westmead,  New South Wales,  2145,  Australia; Recruiting
Peru
      Instituto de Enfermedades Neoplasicas, Lima,  34,  Peru; Recruiting
Puerto Rico
      San Juan City Hospital, San Juan,  00936-7344,  Puerto Rico; Recruiting

Study chairs or principal investigators

Ian W. Flinn, MD, PhD,  Study Chair,  Sidney Kimmel Cancer Center   
Charles A. Linker, MD,  Study Chair,  University of California, San Francisco   

Study ID Numbers:  CDR0000258802; ECOG-E2499; CALGB-50205; CALGB-E2499; NCT00052923
Record last reviewed:  October 2004
Last Updated:  March 28, 2005
Record first received:  January 24, 2003
ClinicalTrials.gov Identifier:  NCT00052923
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08