Trial Information

Treatment of Children With Newly-Diagnosed Low Stage Lymphocyte Predominant Hodgkin Disease (LPHD)

PRIMARY OBJECTIVES:

I. To preserve the excellent cure rate in patients with lymphocyte predominant Hodgkin
disease (LPHD) while employing a treatment strategy that minimizes the exposure to
chemotherapy and radiation therapy in appropriate patients.

II. To estimate the proportion of stage I patients (with a single involved lymph node that
is totally resected) who can be cured with surgery alone.

III. To estimate the proportions of stage I unresected, stage I resected (whose disease has
recurred after observation), and stage II LPHD patients who can be cured with adriamycin
(doxorubicin)/vincristine/prednisone/cyclophosphamide (AV-PC) x 3, with involved field
radiation therapy (IFRT) for those who are not in a CR after chemotherapy.

IV. To reduce the potential for long-term toxicity of LPHD treatment.

OUTLINE: This is a pilot study.

Patients with stage IA disease who underwent confirmed complete resection of a single
involved lymph node at diagnosis undergo observation only*.

Patients with stage IA disease who underwent possible complete resection of a single
involved lymph node at diagnosis undergo imaging at 6-7 weeks after surgery. Patients with a
confirmed complete resection by imaging undergo observation only*. Patients who do not
demonstrate complete resection by imaging proceed to combination chemotherapy with or
without radiotherapy.

Patients with stage IA disease who underwent a fine needle aspiration of a single involved
lymph node OR an incomplete resection of a single involved lymph node at diagnosis may
undergo a second surgery to achieve complete resection. Patients who undergo complete
resection during the second surgery undergo imaging at 6-7 weeks after surgery. Patients
with a confirmed complete resection by imaging undergo observation only*. Patients who do
not undergo a second surgery OR do not achieve complete resection with the second surgery
proceed to combination chemotherapy with or without radiotherapy. Patients with stage IA
disease with involvement of more than 1 lymph node OR stage IIA disease proceed directly to
combination chemotherapy with or without radiotherapy.

NOTE: *Patients with recurrent disease after observation only undergo biopsy and restaging
and then proceed to combination chemotherapy with or without radiotherapy. (AS OF AMENDMENT
#4, THE TREATMENT ARM FOR PATIENTS WHOSE CANCER RECURRED AFTER OBSERVATION ALONE IS NOW
CLOSED)

COMBINATION CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over
10-30 minutes and cyclophosphamide IV over 1 hour on day 1, vincristine IV over 1 minute on
days 1 and 8, and prednisone orally (PO) or IV two or three times daily on days 1-7.
Treatment repeats every 21 days for 3 courses in the absence of disease progression or
unacceptable toxicity. Patients who achieve complete response (CR) after 3 courses of
therapy proceed to follow-up. Patients who do not achieve a CR proceed to involved-field
radiotherapy.

INVOLVED-FIELD RADIOTHERAPY (IFRT): Beginning within 3 weeks after completion of combination
chemotherapy, patients undergo IFRT once daily, 5 days a week for 2.8 weeks (14 treatments).

Patients are followed every 3 months for 2 years, every 6 months for 3 years, annually for 5
years, and then every 5 years for 10 years.