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.

• 131I-omburtamab (Biological), also known as 131I-8H9: Murine IgG1 monoclonal antibody radiolabeled with iodine-131

Primary outcomes

• Overall Survival Rate [3 years]: Overall survival rate at 3 years after the first treatment dose of 131I-omburtamab estimated by the Kaplan-Meier method.

Sex: All, ages: any to 18 Years

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.

Participant flow

Outcome results

• Overall Survival Rate (Primary), Number, Proportion of participants: 131I-omburtamab 0.65 (0.49 to 0.78)

Adverse events

Time frame: Adverse events, including serious, were reported from 1st dose until 3 weeks after the last IMP administration. From 3 weeks after the last IMP administration up to 3 years only SAEs considered related to IMP and new onset for cancers were assessed All cause mortality was assessed up to 3 years.

Serious adverse events by term

Other adverse events by term

Limitations and caveats: The trial was terminated early due to a business strategy decision.

• Results publication: Prasad K, Serencsits BE, Chu BP, Dauer LT, Donzelli M, Basu E, Kramer K, Pandit-Taskar N. Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease. EJNMMI Res. 2024 Jul 31;14(1):70. doi: 10.1186/s13550-024-01127-0. PMID 39083105
• Results publication: Prasad K, Serencsits BE, Chu BP, Dauer LT, Donzelli M, Basu E, Kramer K, Pandit-Taskar N. Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease. Res Sq [Preprint]. 2024 Feb 28:rs.3.rs-3969388. doi: 10.21203/rs.3.rs-3969388/v1. PMID 38464207

• Study Protocol and Statistical Analysis Plan (PDF, 2020-05-01)

• John Roemer, MD, Study director, Y-mAbs Therapeutics