Trial Information

A Phase III Randomized Trial of Intravenous Gammaglobulin Therapy for Patients With Neuroblastoma Associated Opsoclonus-Myoclonus-Ataxia Syndrome Treated With Chemotherapy and Prednisone

PRIMARY OBJECTIVES:

I. Determine whether cyclophosphamide and prednisone with or without immune globulin is a
reasonable baseline standard therapy for pediatric patients with neuroblastoma-associated
opsoclonus-myoclonus-ataxia (OMA) syndrome.

II. Determine whether immunosuppressive therapy with cyclophosphamide and prednisone is an
effective backbone therapy for OMA upon which to build additional treatment for these
patients

SECONDARY OBJECTIVES:

I. Determine whether these regimens improve OMA syndrome in these patients. II. Determine
whether these regimens improve motor coordination in these patients.

III. Determine these regimens improve functional outcome in these patients. IV. Investigate
the biology of neuroblastoma associated OMA, with specific regard to magnetic resonance
imaging (MRI) findings, anti-neuronal antibodies, cerebrospinal fluid (CSF) findings and
tumor biology.

VI. Define better the long-term prognosis for neurologic recovery in the child with
neuroblastoma associated with OMA syndrome. VII. Compare the event-free and overall survival
of patients treated with these regimens.

OUTLINE:

CHEMOTHERAPY: Patients with intermediate-risk or high-risk neuroblastoma receive
chemotherapy (including cyclophosphamide) according to the standard of care for the stage of
primary neuroblastoma, beginning on day 0. Patients with low-risk neuroblastoma (and not
receiving other chemotherapy) receive cyclophosphamide IV over 1 hour on day 0. Treatment
repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable
toxicity. All patients receive oral prednisone twice daily for 3 months and then every other
day for 7-15 months.

IMMUNE GLOBULIN THERAPY: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive immune globulin IV on days -2 and -1, at weeks 4, 8, 12, 16, 20, and
24, and then at months 8, 10, and 12 after therapy. Treatment continues in the absence of
disease progression or unacceptable toxicity. Patients with no response after 6 months go
off treatment.

ARM II: Patients do not receive immune globulin. Patients with unresponsive
opsoclonus-myoclonus-ataxia syndrome after 2 months or progression after 6 months may cross
over to arm I.

Patients are followed during therapy every month for 6 months, at 1 year, and then annually
for up to 10 years.