Trial Information

A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma

PRIMARY OBJECTIVES:

I. To maintain the overall survival (as defined by 4-year "second-event" free survival) for
subjects with high risk Hodgkin lymphoma at or above 95%.

SECONDARY OBJECTIVES:

I. To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or
above 93%.

II. To maintain comparable overall survival (as defined by 4-year "second-event" free
survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response
to the initial 2 cycles of ABVE-PC* by intensifying therapy through the addition of 2 cycles
of ifosfamide/vinorelbine in those with a slow early response.

III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle
of chemotherapy identifies a subject cohort that can be studied in future trials and that is
distinguishable from currently defined RER after 2 cycles.

IV. To describe the patterns of relapse after ABVE-PC* and risk-adapted radiotherapy.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY (ABVE-PC): Patients receive doxorubicin hydrochloride IV over 1-120
minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2, bleomycin sulfate IV
over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8,
etoposide phosphate IV over 1-2 hours on days 1-3, oral prednisone twice daily on days 1-7,
and filgrastim* SC or IV daily beginning on day 4 and continuing until blood counts recover.
Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or
disease progression.

NOTE: *Patients do not receive filgrastim on day 8.

Patients undergo clinical restaging and response assessment after 2 courses of induction
therapy. Patients with rapid early response (RER) or slow early response (SER) proceed to
consolidation therapy. Patients with progressive disease go off study.

CONSOLIDATION THERAPY: Patients are assigned to 1 of 2 consolidation therapy regimens based
on response to induction therapy.

REGIMEN I (RER): Patients receive 2 more courses of ABVE-PC in the absence of unacceptable
toxicity or disease progression.

REGIMEN II (SER): Patients receive ifosfamide IV continuously on days 1-4, vinorelbine
ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on
day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2
courses in the absence of unacceptable toxicity or disease progression. Patients then
receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease
progression.

Patients with a continued response after completion of consolidation therapy proceed to
risk-adapted radiotherapy.

RISK-ADAPTED RADIOTHERAPY: Beginning at 3 weeks after completion of consolidation
chemotherapy, patients undergo radiotherapy once daily, 5 days a week, for 3 weeks (14
fractions) in the absence of unacceptable toxicity or disease progression.

After completion of study therapy, patients are followed up periodically for 10 years.