A Phase III Study for the Treatment of Children and Adolescents With Newly Diagnosed Low Risk Hodgkin Disease
I. Investigate the paradigm of response-based therapy for low-risk Hodgkin's lymphoma by
eliminating involved-field radiotherapy (IFRT) in patients who achieve a complete remission
(CR) after initial chemotherapy.
II. Investigate whether 3 courses of doxorubicin hydrochloride, vincristine, prednisone, and
cyclophosphamide (AV-PC) for the treatment of low-risk Hodgkin's lymphoma is sufficient to
induce CR in at least 80% of patients.
III. Investigate whether patients who experience a low-risk relapse after initial treatment
with chemotherapy alone can be successfully treated with a salvage regimen comprising
ifosfamide and vinorelbine ditartrate with dexamethasone, etoposide phosphate, cisplatin,
and cytarabine (IV/DECA) and IFRT.
IV. Maintain the overall survival for patients with low-risk Hodgkin's lymphoma at or above
V. Determine the prognostic significance of very early response as measured by
fludeoxyglucose-positron emission tomography (FDG-PET) or gallium after the first course of
VI. Evaluate the prognostic significance of elevation of erythrocyte sedimentation rate and
C-reactive protein at the time of diagnosis in patients with low-risk Hodgkin's lymphoma on
CR rate and relapse rate after chemotherapy alone.
VII. Determine the frequency and severity of late effects of therapy, including thyroid
dysfunction, infertility, cardiotoxicity, and second malignant neoplasms.
OUTLINE: This is a multicenter study.
INITIAL CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over
10-30 minutes and cyclophosphamide IV over 1 hour on days 1-2, vincristine IV on days 1 and
8, prednisone orally (PO) on days 1-7, and filgrastim (G-CSF) subcutaneously (SC) on days
3-7 and 9-14. Treatment repeats every 21 days for up to 3 courses in the absence of disease
progression or unacceptable toxicity.
Patients achieving complete remission (CR) proceed to observation. Patients achieving
partial remission proceed to radiotherapy. Patients who have a low-risk relapse after
achieving CR on initial chemotherapy proceed to salvage chemotherapy followed by
radiotherapy. Patients who have stable disease or disease progression go off study.
SALVAGE CHEMOTHERAPY: Patients receive ifosfamide IV continuously on days 1-4, vinorelbine
ditartrate IV over 6-10 minutes on days 1-5, and G-CSF SC or IV beginning on day 6 and
continuing until blood counts recover. Treatment repeats every 21 days for 2 courses.
Patients then receive dexamethasone IV over 15 minutes every 12 hours, etoposide phosphate
IV over 3 hours every 12 hours, and cytarabine IV over 3 hours every 12 hours on days 1 and
2; cisplatin IV over 6 hours on day 1; and G-CSF SC or IV beginning on day 3 and continuing
until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then
proceed to radiotherapy.
INVOLVED-FIELD RADIOTHERAPY (IFRT): Beginning 4 weeks after completion of chemotherapy,
patients undergo IFRT once daily, 5 days a week, for 2.8 weeks. Patients who do not achieve
CR go off study.
After completion of study treatment, patients are followed periodically for up to 10 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Minimum time to a requirement for involved-field radiotherapy (IFRT), requirement for additional chemotherapy and IFRT for retrieval, occurrence of a second malignant neoplasm, or death from any cause
Up to 10 years
Children's Oncology Group
United States: Food and Drug Administration
|Children's Oncology Group||Arcadia, California 91006-3776|