RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Giving radiation therapy after chemotherapy may be an effective treatment for Hodgkin's disease. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and radiation therapy in treating children who have previously untreated stage II, stage III, or stage IV Hodgkin's disease.

Condition	Treatment or Intervention	Phase
stage III childhood Hodgkin's disease stage IV childhood Hodgkin's disease childhood lymphocyte predominant Hodgkin's disease childhood lymphocyte depletion Hodgkin's disease stage II childhood Hodgkin's disease childhood mixed cellularity Hodgkin's disease childhood nodular sclerosis Hodgkin's disease	Drug: bleomycin  Drug: cyclophosphamide  Drug: dacarbazine  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: prednisone  Drug: procarbazine  Drug: vinblastine  Drug: vincristine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the feasibility and toxicity of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) induction in pediatric patients with previously untreated stage II, stage III, or stage IV Hodgkin's disease. II. Determine rates of complete response and rapid early partial response (defined as greater than 70% reduction in the size of a bulky mediastinal mass or nodal aggregate and a negative gallium scan) in these patients treated with 4 courses of BEACOPP. III. Determine whether thallium scans effectively measure response to therapy in these patients treated with this regimen. IV. Evaluate the expression of markers of apoptosis in tumor samples from these patients at diagnosis and at time of relapse, and correlate expression of these markers with response to therapy and overall outcome. V. Determine the utility of seven molecular genetic markers as surrogate markers of genotoxic damage caused by this regimen in these patients. VI. Estimate the incidence of therapy related late effects, including second malignant neoplasms, sterility, cardiac dysfunction, pulmonary restrictive disease, growth abnormalities, and thyroid disease in these patients.

PROTOCOL OUTLINE: Induction: On day 0, patients receive cyclophosphamide IV over 30 minutes, doxorubicin IV over 15-30 minutes, etoposide IV over 1 hour, oral prednisone every 12 hours, and oral procarbazine. On days 1 and 2, patients receive etoposide IV over 1 hour, oral prednisone every 12 hours, and oral procarbazine. On days 3-6, patients receive oral prednisone every 12 hours and oral procarbazine. On day 7, patients receive vincristine IV, bleomycin IV over 5 minutes, and oral prednisone every 12 hours. On days 8-13, patients receive oral prednisone every 12 hours. Beginning on day 8, patients receive filgrastim (G-CSF) subcutaneously until absolute neutrophil counts recover. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Consolidation therapy begins on week 12 or when blood counts recover. Consolidation for rapid early responders (patients with complete response (CR) or rapid early partial response (PR-1) to induction therapy): Females - Patients receive vincristine IV, cyclophosphamide IV over 30 minutes, oral prednisone every 12 hours, and oral procarbazine on day 0. On days 1-6, patients receive oral prednisone every 12 hours and oral procarbazine. On day 7, patients receive vinblastine IV, bleomycin IV over 5 minutes, doxorubicin IV over 15-30 minutes, and oral prednisone every 12 hours. On days 8-13, patients receive oral prednisone every 12 hours. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Males - Patients receive doxorubicin IV over 15-30 minutes, bleomycin IV over 5 minutes, vinblastine IV, and dacarbazine IV on days 0 and 14. Treatment repeats every 28 days for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 3 weeks after completion of chemotherapy, male patients with CR or PR-1 receive radiotherapy 5 days per week to areas of initial disease involvement (total duration of radiotherapy is dependent on initial extent of disease). Consolidation for slow early responders: Patients with slow partial response (PR-2) or stable disease (SD) after 4 courses of induction therapy receive 4 additional courses of induction therapy in the absence of disease progression or unacceptable toxicity. Beginning on day 8, patients receive G-CSF subcutaneously until blood counts recover. Patients should be off G-CSF for more than 24 hours prior to the next course of chemotherapy. Beginning 3 weeks after completion of chemotherapy, male and female patients with PR-2 or SD receive radiotherapy 5 days per week to areas of initial disease involvement (total duration of radiotherapy is dependent on initial extent of disease). Patients are followed every 3 months for 2 years, every 6 months for 1 year, annually for 2 years and then at years 10 and 20.

PROJECTED ACCRUAL: Approximately 25-50 patients will be accrued for this study.

Ages Eligible for Study:  up to  21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven, previously untreated Hodgkin's disease; Stage IV OR Stage II or stage III with B symptoms (at least 1 of the following: unexplained weight loss greater than 10%, unexplained recurrent fever greater than 39 degrees C, or drenching night sweats) AND bulk disease (defined as a mediastinal mass greater than 1/3 of mediastinal thoracic diameter and/or nodal aggregate greater than 10.0 cm)
• The following cellular types are eligible: Mixed cellularity, not otherwise specified (NOS) Lymphocytic depletion, NOS Lymphocytic depletion, diffuse fibrosis; Lymphocytic depletion, reticular Lymphocytic predominance, NOS Lymphocytic predominance, diffuse; Lymphocytic predominance, nodular; Hodgkin's paragranuloma; Hodgkin's granuloma; Hodgkin's sarcoma; Nodular sclerosis, NOS Nodular sclerosis, cellular phase Nodular sclerosis, lymphocytic predominance Nodular sclerosis, mixed cellularity; Nodular sclerosis, lymphocytic depletion Hodgkin's disease, NOS
• Must begin protocol therapy within 42 days of biopsy and 7 days of completion of staging

--Prior/Concurrent Therapy--

• No prior treatment for Hodgkin's disease

--Patient Characteristics--

• Age: 21 and under
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Other: Not pregnant or nursing; Fertile patients must use effective contraception

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Orange County, 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
      Long Beach Memorial Medical Center, Long Beach,  California,  90806,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
Colorado
      Children's Hospital of Denver, Denver,  Colorado,  80218,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5265,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
Missouri
      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States
New Jersey
      Cancer Institute of New Jersey, New Brunswick,  New Jersey,  08901,  United States
      St. Joseph's Hospital and Medical Center, Paterson,  New Jersey,  07503,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
North Carolina
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
      Veterans Affairs Medical Center - Fargo, Fargo,  North Dakota,  58102,  United States
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States
      Children's Hospital of Columbus, Columbus,  Ohio,  43205-2696,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Oregon
      Doernbecher Children's Hospital, Portland,  Oregon,  97201-3098,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84132,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6001,  Australia
Canada, British Columbia
      British Columbia Children's Hospital, Vancouver,  British Columbia,  V6H 3V4,  Canada
Canada, Nova Scotia
      IWK Health Centre, Halifax,  Nova Scotia,  B3J 3G9,  Canada

Study chairs or principal investigators

Kara Kelly,  Study Chair,  Children's Cancer Group   

Study ID Numbers:  CDR0000067222; CCG-59704
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00004010
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08