RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill non-Hodgkin's lymphoma cells. Giving interleukin-2 after radiation therapy, chemotherapy, and peripheral stem cell transplantation may kill more cancer cells.

PURPOSE: Randomizedphase III trial to compare the effectiveness of interleukin-2 with that of observation following radiation therapy, combination chemotherapy, and peripheral stem cell transplantation in treating patients who have refractory or relapsed non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult non-Hodgkin's lymphoma	Drug: cyclophosphamide  Drug: etoposide  Drug: filgrastim  Drug: interleukin-2  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: high-dose chemotherapy  Procedure: interleukin therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the overall and disease-free survival of patients with non-Hodgkin's lymphoma treated with interleukin-2 (IL-2) vs observation only after total-body irradiation, high-dose etoposide, cyclophosphamide, and autologous peripheral blood stem cell transplantation.
• Determine the frequency and severity of toxic effects associated with posttransplantation IL-2 in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease grade (low vs intermediate vs high), chemosensitive disease (yes vs no), partial or complete response after initial induction chemotherapy (yes vs no), and performance status (0-1 vs 2).

• Part I: Autologous peripheral blood stem cells (PBSC) are harvested before study entry. Patients undergo total body irradiation twice a day on days -8 to -5, high-dose etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2. PBSC are reinfused on day 0 and then filgrastim (G-CSF) may be administered subcutaneously or IV on days 0-21.
• Within 28-80 days after PBSC transplantation and after recovery from any toxic effects, patients with no active recurrent or progressive disease are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
• Arm II: Patients undergo observation only. Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 275 patients will be accrued for this study within 3.5-5.9 years.

Ages Eligible for Study:  16 Years   -   60 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven non-Hodgkin's lymphoma (NHL)
• Relapsed after a complete response (CR) or partial response or refractory to prior therapy
• Must meet 1 of the following conditions:
• Low-grade NHL (working formulation B and C) meeting the following criteria:
• At least 2 prior chemotherapy regimens
• Duration of most recent CR less than 1 year
• Received prior separate salvage regimen to determine chemosensitivity
• Intermediate- or high-grade NHL (working formulation D-H and J) meeting the following criteria:
• At least 1 prior chemotherapy regimen
• Separate salvage regimen (as above) required if disease responded to initial chemotherapy
• Transformed lymphomas allowed
• No working formulation A (small lymphocytic) or I (lymphoblastic) lymphoma
• Adequate peripheral blood stem cell collection required
• No CNS involvement
• Part II of the study:
• No known active recurrent or progressive disease 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 former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age:

• 16 to 60

Performance status:

• Part I of the study:
• SWOG 0-1
• Part II of the study:
• SWOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Part II of the study:
• Absolute neutrophil count greater than 500/mm^3
• Platelet count greater than 20,000/mm^3 (no more than 1 transfusion per day)

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT or SGPT no greater than 2 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN
• No history of grade 3 hemorrhagic cystitis from cyclophosphamide

Cardiovascular:

• LVEF normal by echocardiogram or MUGA scan
• No active cardiac disease (e.g., arrhythmias, ischemia) by ECG
• No history of congestive heart failure by chest x-ray
• No history of myocardial infarction or ischemia
• No history of arrhythmia (except bradycardia treated by pacing)
• No S3 gallop rhythm
• No peripheral edema

Pulmonary:

• Parts I and II:
• DLCO or FEV1 at least 65% predicted
• Part II:
• No active pulmonary disease by chest x-ray

Other:

• Parts I and II of the study:
• No allergy to etoposide
• No history of seizure
• No autoimmune disease
• 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
• Not pregnant or nursing
• Fertile patients must us effective contraception
• HIV negative
• Part II of the study:
• No active bacterial, fungal, or viral infection
• Afebrile

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 3 days since prior growth factors
• No prior interleukin-2
• No prior bone marrow or autologous peripheral blood stem cell transplantation
• No concurrent IV immunoglobulin
• No other concurrent cytokines or growth factors

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No concurrent IV or intrathecal methotrexate

Endocrine therapy:

• At least 3 days since prior corticosteroids
• No concurrent corticosteroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No prior involved-field radiotherapy that would preclude total-body irradiation

Surgery:

• No prior allogeneic organ or tissue transplantation

Other:

• Parts I and II of the study:
• Recovered from prior cancer therapy
• At least 3 days since prior pentoxifylline or amphotericin B
• No concurrent pentoxifylline
• No concurrent cardiac medications for control of congestive heart failure or arrhythmias
• No other concurrent therapy for NHL
• Part II of the study:
• No concurrent antibiotic, antifungal, or antiviral agents (except prophylactic therapy) for 3 consecutive days

Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      Arkansas Cancer Research Center at 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
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
Florida
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  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
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States
Michigan
      Josephine Ford Cancer Center at Henry Ford Hospital, Detroit,  Michigan,  48202,  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
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      St. Louis University Hospital Cancer Center, Saint Louis,  Missouri,  63110,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
New Jersey
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018-1095,  United States
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
North Carolina
      Veterans Affairs Medical Center - Salisbury, Salisbury,  North Carolina,  28144,  United States
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States
Texas
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      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
      Swedish Cancer Institute at Swedish Medical Center - First Hill Campus, Seattle,  Washington,  98104,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States
Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada

Study chairs or principal investigators

John A. Thompson, MD,  Study Chair,  Seattle Cancer Care Alliance   

Study ID Numbers:  CDR0000064175; SWOG-9438
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002649
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08