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

Sponsor

Y-mAbs Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03275402

Collaborator

(none)

Enrollment

Locations

Arm

95.7

Anticipated Duration (Months)

4.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma CNS Metastases Leptomeningeal Metastases	Biological: 131I-omburtamab	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Patients will receive up to two cycles of intracerebroventricular 131I-omburtamab. Safety and efficacy will be investigated with short-term follow-up at 26 weeks after treatment and with long-term follow-up for up to 3 years following treatment.Patients will receive up to two cycles of intracerebroventricular 131I-omburtamab. Safety and efficacy will be investigated with short-term follow-up at 26 weeks after treatment and with long-term follow-up for up to 3 years following treatment.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 11, 2018

Anticipated Primary Completion Date :

May 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 131I-omburtamab One treatment cycle of 131I-omburtamab consists of 1 dose at 50mCi at week 1. For Japan only one treatment cycle of 131I-omburtamab consists of 2 doses: 2mCi at week 1 and 50mCi at week 2. First cycle is initiated right after confirmation of eligibility at week 1. At week 5 (week 6 for Japan) the participant will be evaluated for safety and if eligible, receive a second cycle of 131I-omburtamab. Secondary efficacy endpoints will be evaluated at week 26 and primary efficacy endpoint will be evaluated at week 156.	Biological: 131I-omburtamab Murine IgG1 monoclonal antibody radiolabeled with iodine-131 Other Names: 131I-8H9

Arm

Intervention/Treatment

Experimental: 131I-omburtamab

One treatment cycle of 131I-omburtamab consists of 1 dose at 50mCi at week 1. For Japan only one treatment cycle of 131I-omburtamab consists of 2 doses: 2mCi at week 1 and 50mCi at week 2. First cycle is initiated right after confirmation of eligibility at week 1. At week 5 (week 6 for Japan) the participant will be evaluated for safety and if eligible, receive a second cycle of 131I-omburtamab. Secondary efficacy endpoints will be evaluated at week 26 and primary efficacy endpoint will be evaluated at week 156.

Biological: 131I-omburtamab

Murine IgG1 monoclonal antibody radiolabeled with iodine-131

Other Names:

131I-8H9

Outcome Measures

Primary Outcome Measures

Overall survival rate [3 years]
Overall survival rate at 3 years after the first treatment dose of 131I-omburtamab.

Secondary Outcome Measures

Overall survival [3 years]
Overall survival at 3 years after the first treatment dose of 131I-omburtamab.
Objective response rate (ORR) [3 years]
ORR is defined and assessed as a combination of partial response and complete response as defined by the RANO criteria and CSF cytology.
Objective response rate (ORR) [3 years]
ORR according to CSF cytology. ORR is defined and assessed as a combination of partial response and complete response.
CNS progression free survival (PFS) [6 month]
CNS PFS will be assessed at 6 months after the first treatment dose of 131I-omburtamab by comparing baseline radiological scans by MRI to radiological scans conducted 26 weeks after 131I-omburtamab treatment.
Dosimetry of 131I-omburtamab [2 weeks]
Whole-body, organ, blood, and CSF radiation dosimetry.
Assessment of peak plasma concentration (Cmax) of 131I-omburtamab [Baseline, 30 minutes, 1 hour, 4 hour, 1, 2, 3 and 7 days]
Cmax will be calculated and summarized with descriptive statistics.
Assessment of residence time of 131I-omburtamab [Baseline, 30 minutes, 1 hour, 4 hour, 1, 2, 3 and 7 days.]
Residence time will be calculated and summarized with descriptive statistics.
Assessment of elimination half-life of 131I-omburtamab [Baseline, 30 minutes, 1 hour, 4 hour, 1, 2, 3 and 7 days.]
Elimination half-life will be calculated and summarized with descriptive statistics.
Safety of 131I-omburtamab [3 years]
The frequency, type, and duration of treatment-emergent severe adverse events and serious adverse events, including clinically significant laboratory abnormalities. All adverse events will be graded according to CTCAE, version 4.0.
Performance assessment [3 years]
Performance assessment to monitor gross changes in neurological function is performed at week 26 and subsequently every 6 months during trial period using Lansky (< 16 years) and Karnofsky (≥ 16 years).

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027
2	University of Florida	Gainesville	Florida	United States	32611
3	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
6	M.D. Anderson Cancer Center	Houston	Texas	United States	77030
7	Division of Haematology/Oncology The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
8	Rigshospitalet	København		Denmark	2100
9	Klinik Schwabing Kinderklinik der Technischen Universität	München		Germany	80804
10	Department of Pediatric Oncology Fukushima Medical University Hospita	Fukushima City		Japan	960-1295
11	Hospital Sant Joan de Déu	Barcelona		Spain	08010
12	The Royal Marsden	Sutton	Surrey	United Kingdom	SM2 5PT