Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy and Radiation Therapy in Treating Children With Previously Untreated Stage II, Stage III, or Stage IV Hodgkin's Disease

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	21 and under	NCI	COG-59704 NCT00004010, CCG-59704

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.

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

Expected Enrollment

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

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.

Kelly M, Hutchinson R, Sposto R, et al.: BEACOPP chemotherapy is a highly effective regimen in children and adolescents with advanced stage Hodgkin's disease: results from Children's Cancer Group study CCG-59704. [Abstract] Eur J Haematol 75 (Suppl 65): A-WP07, 72, 2004.

Shiramizu B, Morris E, Perkins S, et al.: Identification of patient specific primers (PSPs) of IgH and TCR-y regions by nested PCR in CD20 positive Hodgkin disease: a Children's Cancer Group report (CCG). [Abstract] Ann Oncol 13(suppl 2): A-389, 112, 2002.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Kara Kelly, MD, Protocol chair		Ph: 212-305-3374 Email: kk291@columbia.edu

Registry Information
Official Title		Pilot Study for the Treatment of Children with Newly Diagnosed Advanced Stage Hodgkin's Disease: Upfront Dose Intensive Chemotherapy
Trial Start Date		1999-10-15
Registered in ClinicalTrials.gov		NCT00004010
Date Submitted to PDQ		1999-07-26
Information Last Verified		2005-02-17
NCI Grant/Contract Number		CA57746