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

NCT ID: NCT03275402

Last Updated: 2024-02-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-11
• Study Completion Date: 2023-06-02

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.

Conditions

Neuroblastoma; CNS Metastases; Leptomeningeal Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

131I-omburtamab

One treatment cycle of 131I-omburtamab consists of one dosimetry dose (2 mCi ) (for subjects enrolled on Version 1-7 of Protocol 101) and one treatment dose (50 mCi) for up to 2 cycles of length 5 weeks (for subjects enrolled on Version 1-7 of Protocol 101) or 4 weeks (for subject enrolled after Version 7 of Protocol 101). For Japan only, the first cycle consisted of one dosimetry dose (2 mCi ) week 1 one treatment dose (50 mCi) week 2. If eligible a second cycle of 50 mCi 131I-omburtamab was given at week 6. For subjects below 3 and 1 years of age, the treatment dose was reduced by 33% and 50%, respectively.

Group Type: EXPERIMENTAL

131I-omburtamab

Intervention Type: BIOLOGICAL

Murine IgG1 monoclonal antibody radiolabeled with iodine-131

Interventions

131I-omburtamab

Murine IgG1 monoclonal antibody radiolabeled with iodine-131

Intervention Type: BIOLOGICAL

Other Intervention Names

131I-8H9

Eligibility Criteria

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.

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Y-mAbs Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Roemer, MD

Role: STUDY_DIRECTOR

Y-mAbs Therapeutics

Locations

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

Copenhagen, , Denmark

Department of Pediatric Oncology Fukushima Medical University Hospita

Fukushima, , Japan

Hospital Sant Joan de Déu

Barcelona, , Spain

Countries

United States; Denmark; Japan; Spain

References

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.

Reference Type: DERIVED

PMID: 39083105 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38464207 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

101

Identifier Type: -

Identifier Source: org_study_id