RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high energy x-rays to damage tumor cells. Combining more than one drug or combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy, with or without chemotherapy, with chemotherapy alone in treating patients with stage I or stage IIA Hodgkin's disease.

Condition	Treatment or Intervention	Phase
adult lymphocyte predominant Hodgkin's disease adult lymphocyte depletion Hodgkin's disease adult mixed cellularity Hodgkin's disease adult nodular sclerosis Hodgkin's disease stage II adult Hodgkin's disease stage I adult Hodgkin's disease	Procedure: chemotherapy  Procedure: radiation therapy  Drug: bleomycin  Drug: dacarbazine  Drug: doxorubicin  Drug: vinblastine	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the 12-year survival of patients with clinical stage I-IIA Hodgkin's disease treated with radiotherapy with or without doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus ABVD only. II. Compare the freedom from progression at 5 and 10 years in patients treated with these regimens. III. Compare the complete remission rate, freedom from secondary disease progression at 5 and 10 years, and cause-specific survival at 5, 10, and 15 years in patients treated with these regimens. IV. Compare the short- and long-term toxicity of these regimens in these patients. V. Compare the quality of life of patients in patients treated with these regimens.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified by center. Patients who are under age 40 and have lymphocyte-predominant or nodular sclerosing histology, an erythrocyte sedimentation rate less than 50, and fewer than 4 disease sites (supradiaphragmatic or pelvic node sites) are assigned to cohort 1 (good prognosis). All other patients are assigned to cohort 2 (poor prognosis). Cohort 1: Arm I: Patients with supradiaphragmatic disease undergo radiotherapy to the supradiaphragmatic lymph node areas (mantle region), spleen, and para-aortic lymph nodes 5 days a week for 4 weeks. Patients with pelvic disease undergo radiotherapy to an "inverted-Y" field (excluding the spleen) 5 days a week for 4 weeks. Arm II: Patients receive doxorubicin, bleomycin, vinblastine, and dacarbazine IV on days 1 and 15 (ABVD). Treatment continues every 4 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Patients with complete remission (CR) after course 2 receive 2 additional courses past CR. Patients with partial remission (PR) after course 2 receive 4 additional courses past PR. Patients with unconfirmed/uncertain complete remission (CRu) receive 2-4 additional courses past CRu. Cohort 2: Arm III: Patients receive ABVD as in arm II, followed 4-6 weeks later by concurrent radiotherapy to the mantle region and upper abdomen to the level of L2 5 days a week for 4 weeks. Alternatively, radiotherapy may also be administered sequentially to the mantle region 5 days a week for 4 weeks and then to the upper abdomen to the level of L2 5 days a week for 4 weeks. Arm IV: Patients receive ABVD only as in arm II. Patients with disease progression after treatment in arms II or IV are considered for radiotherapy. Quality of life is assessed on day 1 of each course of chemotherapy (arms II-IV) and on day 28 of the last course of chemotherapy (arms II and IV); on the first and final days of radiotherapy (arms I and III); at 4 weeks and at 3, 6, and 12 months after completion of radiotherapy (arms I and III) or chemotherapy (arms II and IV); and then annually for 2-10 years. Patients are followed at months 3, 6, and 12 and then annually thereafter.

PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study within 7.5 years.

Ages Eligible for Study:  16 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven stage I-IIA Hodgkin's disease; Needle core biopsy is sufficient for diagnosis; Needle aspirate not sufficient for diagnosis; Any histology allowed
• Up to 1 extranodal site allowed if encompassable in a standard radiotherapy field; No extranodal disease that cannot be included in such a field (e.g., lung, bone)
• No B symptoms
• Iliofemoral, inguinal, or parailiac nodal involvement allowed; No other intra-abdominal disease
• Complete excision at biopsy allowed
• Considered eligible for radiotherapy by radiation and medical oncologists
• No stage IA disease that might be treated with involved-field radiotherapy only and meets the following criteria: Lymphocyte-predominant or nodular sclerosing histology; Disease bulk less than 3 cm; Erythrocyte sedimentation rate less than 50; Unilateral high-neck only disease, defined by 1 of the following conditions: Disease located above the upper border of the thyroid cartilage; Isolated epitrochlear adenopathy
• No bulky adenopathy, defined by 1 of the following criteria: Palpable nodal mass greater than 10 cm in diameter; Mediastinal mass with a maximum diameter of at least one-third the maximum chest wall diameter
• If supradiaphragmatic disease present: No clinical splenic involvement, defined by 1 of the following criteria: Spleen palpable on physical exam and enlarged on imaging studies; Spleen showing focal abnormalities on imaging study consistent with Hodgkin's disease
• No lytic or blastic lesions on plain radiograph or abnormalities on bone scan consistent with Hodgkin's disease
• No pleural effusions or ascites; Pleural thickening or "blunting" of costophrenic angle only on x-ray may be allowed

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent growth factors during the first course of chemotherapy
• Chemotherapy: No prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; No prior radiotherapy
• Surgery: See Disease Characteristics; No prior staging laparotomy
• Other: No other concurrent anticancer therapy; No concurrent cardiac medications

--Patient Characteristics--

• Age: 16 and over
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Granulocyte count at least 1,500/mm3; Platelet count at least 125,000/mm3
• Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN) (unless elevation due to hemolytic anemia)
• Renal: Creatinine no greater than 2 times ULN
• Cardiovascular: No symptomatic congestive heart failure or coronary artery disease; No known valvular disease (other than asymptomatic mitral valve prolapse); No congenital heart disease (other than asymptomatic atrial septal defects); Hypertension controlled with drug therapy allowed
• Pulmonary: FVC, FEV1, and DLCO at least 60% predicted for patients with symptomatic lung disease or asthma controlled by medication
• Other: HIV negative; No clinical diagnosis of AIDS; No other major medical illness that would preclude study therapy; No other prior or concurrent malignancy (including carcinoma in situ of the cervix) except adequately treated basal cell skin cancer; Not pregnant; Negative pregnancy test; Fertile patients must use effective contraception

Colorado
      CCOP - Colorado Cancer Research Program, Inc., Denver,  Colorado,  80209-5031,  United States
Georgia
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States
Illinois
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68131,  United States
New Jersey
      Cancer Institute of New Jersey, New Brunswick,  New Jersey,  08901,  United States
      Cancer Institute of New Jersey at Hamilton, Hamilton,  New Jersey,  08690,  United States
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
      Kimball Medical Center, Lakewood,  New Jersey,  08701,  United States
      Riverview Medical Center - Booker Cancer Center, Red Bank,  New Jersey,  07701,  United States
      Somerset Medical Center, Somerville,  New Jersey,  08876,  United States
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018-1095,  United States
New York
      University of Rochester Cancer Center, Rochester,  New York,  14642,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
Ohio
      CCOP - Toledo Community Hospital Oncology Program, Toledo,  Ohio,  43623-3456,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213-3489,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
      Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville,  Tennessee,  37212,  United States
Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, British Columbia
      British Columbia Cancer Agency, Vancouver,  British Columbia,  V5Z 4E6,  Canada
      British Columbia Cancer Agency - Vancouver Island Cancer Centre, Victoria,  British Columbia,  V8R 6V5,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, New Brunswick
      Doctor Leon Richard Oncology Centre, Moncton,  New Brunswick,  E1C 8X3,  Canada
      Moncton Hospital, Moncton,  New Brunswick,  E1C 6ZB,  Canada
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada
Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada
Canada, Ontario
      Algoma District Medical Group, Sault Sainte Marie,  Ontario,  P6B 1Y5,  Canada
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Credit Valley Hospital, Mississauga,  Ontario,  L5M 2N1,  Canada
      Hotel Dieu Health Sciences Hospital - Niagara, St. Catharines,  Ontario,  L2R 5K3,  Canada
      Humber River Regional Hospital, Weston,  Ontario,  M9N 1N8,  Canada
      Lakeridge Health Oshawa, Oshawa,  Ontario,  L1G 2B9,  Canada
      Mount Sinai Hospital - Toronto, Toronto,  Ontario,  M5G 1X5,  Canada
      Northeastern Ontario Regional Cancer Centre, Sudbury, Sudbury,  Ontario,  P3E 5J1,  Canada
      Northwestern Ontario Regional Cancer Centre, Thunder Bay, Thunder Bay,  Ontario,  P7A 7T1,  Canada
      Toronto General Hospital, Toronto,  Ontario,  M5G 2C4,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
      York County Hospital, Newmarket,  Ontario,  L3Y 2P9,  Canada
Canada, Quebec
      Centre Hospitalier de l'Universite de Montreal, Montreal,  Quebec,  H2L-4M1,  Canada
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada
Canada, Saskatchewan
      Saskatoon Cancer Centre, Saskatoon,  Saskatchewan,  S7N 4H4,  Canada
Italy
      Azienda Ospedaliera di Perugia, Perugia,  06122,  Italy
      Spedali Civili, Brescia,  25124,  Italy
South Africa
      Pretoria Academic Hospitals, Pretoria,  0001,  South Africa
United Kingdom, England
      Royal South Hants Hospital, Southampton,  England,  SO14 0YG,  United Kingdom

Study chairs or principal investigators

Ralph Melbourne Meyer,  Study Chair,  National Cancer Institute of Canada   
Jane N. Winter,  Study Chair

Study ID Numbers:  CDR0000063481; CAN-NCIC-HD6; NCI-V94-0427
Record last reviewed:  November 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002561
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08