RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy.

PURPOSE: Phase II trial to compare the effectiveness of different combination chemotherapy regimens with or without radiation therapy or peripheral stem cell transplantation in treating children who have Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
stage II childhood Hodgkin's lymphoma stage I childhood Hodgkin's lymphoma stage III childhood Hodgkin's lymphoma stage IV childhood Hodgkin's lymphoma recurrent/refractory childhood Hodgkin's lymphoma	Drug: bleomycin  Drug: chlorambucil  Drug: cisplatin  Drug: dacarbazine  Drug: doxorubicin  Drug: etoposide  Drug: ifosfamide  Drug: melphalan  Drug: prednisolone  Drug: procarbazine  Drug: vinblastine  Drug: vincristine  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine whether the current survival figures are maintained and long-term sequelae of treatment are minimized in children or adolescents with stage I-III Hodgkin's lymphoma after receiving the following regimen, which reduces exposure to chemotherapy and radiotherapy: chlorambucil, vinblastine, prednisolone, and procarbazine (ChIVPP) and doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) with etoposide, prednisolone, ifosfamide, and cisplatin (EPIC), radiotherapy, high-dose melphalan, and/or autologous peripheral blood stem cell transplantation (APBSCT).
• Determine whether the survival figures are improved in children or adolescents with stage IV Hodgkin's lymphoma or inadequate response to initial therapy after receiving ChIVPP and ABVD with EPIC, radiotherapy, high-dose melphalan, and APBSCT.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 3 treatment groups based on disease status.

• Group 1 (stage I disease): All patients with mixed cellularity and younger patients with any subtype are assigned to subgroup A. Older patients without mixed cellularity are assigned to subgroup A or B based on the decision of the physicians and patients/parents. Subgroup A: Patients receive 2 courses of the hybrid regimen. One course of the hybrid regimen comprises regimen ChIVPP followed by regimen ABVD. Regimen ChIVPP comprises vinblastine IV on days 1 and 8 and oral chlorambucil, oral procarbazine, and oral prednisolone (PRDL) daily on days 1-14. Regimen ABVD comprises doxorubicin IV over 6 hours, bleomycin IV over 15-30 minutes, vincristine IV, and dacarbazine IV over 15 minutes on days 1 and 14. Patients with relapsed disease receive etoposide IV over 1 hour on days 1-4, oral PRDL and ifosfamide IV over 1 hour on days 1-5, and cisplatin IV over 24 hours on day 10 (EPIC). Treatment with EPIC continues every 3 weeks for a total of 6 courses. Patients then undergo radiotherapy. Patients with poor response after radiotherapy receive consolidation with high-dose melphalan (L-PAM) IV over 30-90 minutes, followed at least 12 hours later by autologous peripheral blood stem cell transplantation (APBSCT) (if there is no bone marrow involvement at the time of relapse). Subgroup B: Patients not in subgroup A may either receive chemotherapy as outlined or radiotherapy depending on clinician and patient discussion. Patients with relapsed disease after radiotherapy receive 3 courses of the hybrid regimen. If relapse occurs outside the initial radiotherapy field, then further radiotherapy is administered.
• Group 2 (stage II or III disease): Patients receive 3 courses of the hybrid regimen. Patients with relapsed disease receive 4 courses of EPIC. Patients with complete remission (CR) or good partial remission (GPR) after the fourth course of EPIC receive 2 additional courses of EPIC followed by radiotherapy. Patients without CR or GPR after the fourth course of EPIC undergo radiotherapy followed by L-PAM and APBSCT as in group 1, subgroup A.
• Group 3 (stage IV or inadequate response to initial therapy): Patients receive 2 courses the hybrid regimen. Patients with CR or GPR after the second course of ABVD are assigned to subgroup C. Patients without CR or GPR after the second course of ABVD are assigned to subgroup D. Subgroup C: Patients receive 2 additional courses of the hybrid regimen. Patients with relapsed disease after the fourth course of ABVD receive 4 courses of EPIC followed by radiotherapy, L-PAM, and APBSCT as in group 1, subgroup A. Subgroup D: Patients receive 4 courses of EPIC followed by radiotherapy, L-PAM, and APBSCT as in group 1, subgroup A. Patients are followed every 2 months for 1 year, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 260 patients (75 with stage I disease, 150 with stage II or III disease, and 35 with stage IV disease) will be accrued for this study within 5 years.

Ages Eligible for Study:  up to  17 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven Hodgkin's lymphoma
• Stage I-IV
• No posttransplantation Hodgkin's lymphoma
• Mediastinal syndrome allowed

PATIENT CHARACTERISTICS: Age:

• Under 18 at diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No other previously treated malignancy
• No DNA repair defect syndromes

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Ireland
      Our Lady's Hospital for Sick Children, Crumlin,  12,  Ireland; Recruiting
United Kingdom, England
      Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust, Cambridge,  England,  CB2 2QQ,  United Kingdom; Recruiting
      Birmingham Children's Hospital, Birmingham,  England,  B4 6NH,  United Kingdom; Recruiting
      Bristol Royal Hospital for Children, Bristol,  England,  BS2 8BJ,  United Kingdom; Recruiting
      Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester,  England,  M27 4HA,  United Kingdom; Recruiting
      Children's Hospital - Sheffield, Sheffield,  England,  S10 2TH,  United Kingdom; Recruiting
      Great Ormond Street Hospital for Children NHS Trust, London,  England,  WC1N 3JH,  United Kingdom; Recruiting
      Leicester Royal Infirmary, Leicester,  England,  LE1 5WW,  United Kingdom; Recruiting
      Meyerstein Institute of Oncology at University College of London Hospitals, London,  England,  WIT 3AA,  United Kingdom; Recruiting
      Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne,  England,  NE7 7DN,  United Kingdom; Recruiting
      Oxford Radcliffe Hospital, Oxford,  England,  0X3 9DU,  United Kingdom; Recruiting
      Queen's Medical Centre, Nottingham,  England,  NG7 2UH,  United Kingdom; Recruiting
      Royal Liverpool Children's Hospital, Alder Hey, Liverpool,  England,  L12 2AP,  United Kingdom; Recruiting
      Royal Marsden NHS Foundation Trust - Surrey, Sutton,  England,  SM2 5PT,  United Kingdom; Recruiting
      Saint Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom; Recruiting
      Southampton General Hospital, Southampton,  England,  SO16 6YD,  United Kingdom; Recruiting
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting
United Kingdom, Northern Ireland
      Royal Belfast Hospital for Sick Children, Belfast,  Northern Ireland,  BT12 6BE,  United Kingdom; Recruiting
United Kingdom, Scotland
      Aberdeen Royal Infirmary, Aberdeen,  Scotland,  AB25 2ZN,  United Kingdom; Recruiting
      Royal Hospital for Sick Children, Glasgow,  Scotland,  G3 8SJ,  United Kingdom; Recruiting
      Royal Hospital for Sick Children, Edinburgh,  Scotland,  United Kingdom; Recruiting

Study chairs or principal investigators

Martin Hewitt, MD, BSc, FRCP, FRCPCH,  Study Chair,  Queen's Medical Centre   

Study ID Numbers:  CDR0000068901; UKCCSG-HD-2000-02; EU-20108; NCT00025064
Record last reviewed:  April 2002
Last Updated:  April 4, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025064
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08