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

One 131I-omburtamab treatment cycle takes 4 weeks and includes a treatment dose, and an

observation period and post-treatment evaluations.

One 131I-omburtamab treatment cycle for Japan only takes 5 weeks and includes 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 1 (week 2

for Japan) 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 5 (week 6

for Japan) 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.

In case the patient has a subsequent relapse in the CNS/LM after 131I-omburtamab therapy

during the follow-up period, re-treatment to target minimal residual disease can be

considered and allowed.