131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases

One 131I-omburtamab treatment cycle takes 5 weeks and includes a dosimetry dose, a treatment
dose, an observation period and post-treatment evaluations.

- A dosimetry dose (2mCi) of 131I-omburtamab is administered during week 1 followed by
blood/cerebral spinal fluid (CSF) samples and whole-body scintigraphy at predefined
intervals during the following 48 hours after treatment.

- A therapeutic dose (50mCi) of 131I-omburtamab is administered during week 2 followed by
a 3-week observation period that includes a repeated MRI, CSF cytology, and safety
monitoring.

- A second treatment cycle of 131I-omburtamab is administered during week 6 if there is no
objective disease progression week 5 after the first injection, and the participant is
presenting without unexpected and clinical significant Grade 4 toxicity. For
participants with ongoing Grade 3 toxicity a second doing cycle will take place
according to the discretion of the investigator.

Participants can be treated in an outpatient setting or may be admitted as inpatients for
both the dosimetry and the therapeutic injections.

Participants completing at least one treatment period will first enter a follow-up period
through week 26 and thereafter the long-term follow-up where patients will be evaluated for
up to 3 years post-131I-omburtamab treatment where after the trial is ended

Participants will be monitored for adverse events during and after 131I-omburtamab injection
and will have pre- and post-treatment clinical assessments including neurologic examination,
hematology and serum chemistry, blood and CSF cultures, endocrinology assessments, CSF
analysis, and, pre- and post 131I-omburtamab performance testing. Performance testing will be
performed at trial baseline, at week 26 and every 6 months during trial period.

Inclusion Criteria:

- Patients must have a histologically confirmed diagnosis of neuroblastoma with relapse
in the central nervous system or in the meninges (leptomeningeal).

- Patients must be between the ages of birth and 18 years at the time of screening.

- Patients must have a life expectancy of at least 3 months.

Exclusion Criteria:

- Patients with primary neuroblastoma in central nervous system.

- Patients must not have an uncontrolled life-threatening infection.

- Patients must not have received cranial or spinal irradiation less than 3 weeks prior
to first dose of 131I-omburtamab in this trial.

- Patients must not have received systemic chemotherapy (corticosteroids not included)
less than 3 weeks prior to enrollment in this trial.

- Patients must not have severe major non-hematologic organ toxicity; specifically, any
renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity must fall
below Grade 3 prior to enrollment in this trial. Patients with stable neurological
deficits (due to brain tumor) are not excluded. Patients with Grade 3 or lower hearing
loss are not excluded.