Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease

• Event-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Event-free survival defined as the time to treatment failure (disease progression, disease recurrence, biopsy positive residual after completion of all protocol therapy), occurrence of a second malignant neoplasm, or death from any cause
  
  

• Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  
• Disease response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  assessed by modified RECIST criteria
  
  
• Toxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  Incidence of Grade 3 or 4 non-hematologic toxicity that doesn't respond to treatment within 7 days despite recommended therapy modification assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  
  

OBJECTIVES:

• Compare response-based therapy with doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without dexamethasone, etoposide, cytarabine, cisplatin, and/or radiotherapy in children with intermediate-risk Hodgkin's lymphoma.
• Determine whether radiotherapy can be eliminated from this regimen based upon early and complete response to multiagent chemotherapy in these patients.
• Determine whether the addition of dexamethasone, etoposide, cytarabine, cisplatin, and filgrastim (G-CSF) improves outcome in those patients with a slow early response to standard chemotherapy.
• Compare the frequency and severity of late effects of this therapy, including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity, and second malignant neoplasms, in patients treated with these regimens.
• Correlate results from biology and late effects studies with response to therapy, event-free survival, and overall survival in these patients.

OUTLINE: This is a randomized, multicenter study.

• Initial chemotherapy (ABVE-PC): Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or subcutaneously (SC) and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 4 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease.

At the end of initial chemotherapy, patients undergo evaluation for response. Patients with less than 60% disease reduction are considered to have slow early response (SER). Patients with 60% or more disease reduction are considered to have rapid early response (RER).

• RER: Patients with RER receive 2 additional courses of ABVE-PC chemotherapy. After the additional course, patients with less than a complete response undergo radiotherapy 5 days a week. Patients with a complete response are randomized to receive either radiotherapy or no further treatment.

• SER: Patients with SER are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2 and cisplatin IV over 6 hours on day 1. Patients also receive G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients then undergo radiotherapy.
  • Arm II: Patients receive 2 additional courses of ABVE-PC chemotherapy. Patients then undergo radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study within 5-5.5 years.