Trial Information

European Infant Neuroblastoma Study - Stage 2, 3, 4, and 4S; MYCN Amplified Tumors

OBJECTIVES:

- Determine the survival of infants with newly diagnosed stage II, III, IV, or IVS
neuroblastoma with MYCN amplification treated with etoposide, carboplatin,
cyclophosphamide, doxorubicin, and vincristine followed by surgery and busulfan and
melphalan with autologous peripheral blood stem cell or bone marrow transplantation.

- Determine whether there are prognostic criteria that could be used in future
therapeutic stratification of these patients.

OUTLINE: This is a multicenter study.

Patients receive VP-CARBO chemotherapy comprising etoposide IV over 2 hours and carboplatin
IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses. Patients then
receive CADO chemotherapy comprising cyclophosphamide IV over 1 hour on days 1-5,
doxorubicin IV over 6 hours on days 4 and 5, and vincristine IV on days 1 and 5. Treatment
repeats every 21 days for 2 courses.

Patients receive filgrastim (G-CSF) subcutaneously daily for 5 days. Patients undergo
leukapheresis to collect peripheral blood stem cells (PBSC). Patients who do not mobilize
sufficient cells undergo bone marrow harvest.

Patients eligible for surgery undergo surgical resection. Patients with stage IV disease
with less than complete response of metastatic disease after initial chemotherapy are
removed from the study.

Beginning within 2 weeks after surgery, patients receive 1 additional course of VP-CARBO
chemotherapy followed by 1 additional course of CADO chemotherapy.

After at least 3 weeks, patients receive high-dose chemotherapy comprising busulfan IV over
24 hours on days -7 to -3 and melphalan IV on day -2. PBSC or bone marrow are reinfused on
day 0.

At least 2 months after the completion of high-dose chemotherapy and bone marrow or PBSC
transplantation, patients undergo radiotherapy to the primary site, according to
preoperative imaging studies. Patients are treated with oral tretinoin after megatherapy.

Patients are followed within 6 months and then annually for 5 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years.