Trial Information

Protocol For The Treatment Of Children And Adolescents With Hodgkin's Disease

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.