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

Phase 2

Terminated

Conditions: CNS Metastases
Leptomeningeal Metastases
Neuroblastoma

Registration Number: NCT03275402

Lead Sponsor: Y-mAbs Therapeutics

Brief Summary: Children with a neuroblastoma diagnose and central nervous system (CNS)/leptomeningeal metastases will be given up to 2 rounds of intracerebroventricular treatment with a radiolabelled monoclonal antibody, 131I-omburtamab to evaluate efficacy and safety

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 52

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (8): Childrens Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
M.D. Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Rigshospitalet
🇩🇰
København, Denmark
Department of Pediatric Oncology Fukushima Medical University Hospita
🇯🇵
Fukushima City, Japan
Hospital Sant Joan de Déu
🇪🇸
Barcelona, Spain
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States