Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma

OBJECTIVES:

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
97%.

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
chemotherapy.

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.

Inclusion Criteria:

- Histologically confirmed Hodgkin's lymphoma meeting the following criteria:

- Newly diagnosed disease

- Stage IA OR stage IIA without bulky disease

- No lymphocyte-predominant histology

- Staging on this study will be determined by the clinical stage; surgical staging is
strongly discouraged, except for the rare situation of equivocal imaging studies
below the diaphragm

- Patients may not have received any previous chemotherapy or radiation therapy;
patients may not have received systemic corticosteroids within 30 days of enrollment
on this protocol; steroids used for treatment of contrast agent allergy required for
computed tomography (CT) scans are acceptable

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^3

- Total bilirubin =< 1.5 x normal

- Alanine (ALT) =< 2.5 x normal

- Shortening fraction >= 27% by echocardiogram OR ejection fraction >= 50% by
multi-gated acquisition (MUGA)

- No pathologic prolongation of QTc interval on 12-lead electrocardiography (ECG)

- Female patients of childbearing potential must have a negative pregnancy test

- Lactating females must agree that they will not breastfeed a child while on this
study

- Fertile patients must use effective contraception

- Males and females of reproductive potential may not participate unless they have
agreed to use an effective contraceptive method

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met