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

Neuroblastoma Clinical Trial

Official title:

A Multicenter Phase 2/3 Trial of the Efficacy and Safety of Intracerebroventricular Radioimmunotherapy Using 131I-omburtamab for Neuroblastoma Central Nervous System/Leptomeningeal Metastases

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03275402
• Other study ID #: 101
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: December 11, 2018
• Est. completion date: June 2, 2023

Study information

• Verified date: January 2024
• Source: Y-mAbs Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Terminated
• Enrollment: 52
• Est. completion date: June 2, 2023
• Est. primary completion date: June 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• CNS Metastases
• Leptomeningeal Metastases
• Meningeal Carcinomatosis
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Neuroblastoma

Intervention

Biological:
• 131I-omburtamab
Murine IgG1 monoclonal antibody radiolabeled with iodine-131

Locations

Country	Name	City	State
Denmark	Rigshospitalet	København
Japan	Department of Pediatric Oncology Fukushima Medical University Hospita	Fukushima City
Spain	Hospital Sant Joan de Déu	Barcelona
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Y-mAbs Therapeutics

Countries where clinical trial is conducted

United States,  Denmark,  Japan,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Rate	Overall survival rate at 3 years after the first treatment dose of 131I-omburtamab estimated by the Kaplan-Meier method.	3 years