131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases
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|ClinicalTrials.gov Identifier: NCT03275402|
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : November 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma CNS Metastases Leptomeningeal Metastases||Biological: 131I-omburtamab||Phase 2 Phase 3|
One 131I-omburtamab treatment cycle takes 5 weeks and includes a dosimetry dose, a treatment dose, an observation period and post-treatment evaluations.
- 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 2 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 6 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|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.|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||October 2018|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2022|
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 6 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.
Murine IgG1 monoclonal antibody radiolabeled with iodine-131
Other Name: 131I-8H9
- Overall survival rate [ Time Frame: 3 years ]Overall survival rate at 3 years after the first treatment dose of 131I-omburtamab.
- Overall survival [ Time Frame: 3 years ]Overall survival at 3 years after the first treatment dose of 131I-omburtamab.
- Objective response rate (ORR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 2 weeks ]Whole-body, organ, blood, and CSF radiation dosimetry.
- Assessment of peak plasma concentration (Cmax) of 131I-omburtamab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03275402
|Contact: Joris Wilmsfirstname.lastname@example.org|
|United States, California|
|Childrens Hospital Los Angeles||Not yet recruiting|
|Los Angeles, California, United States, 90027|
|United States, Florida|
|University of Florida||Not yet recruiting|
|Gainesville, Florida, United States, 32611|
|United States, Indiana|
|Riley Hospital for Children||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Not yet recruiting|
|New York, New York, United States, 10065|
|United States, Ohio|
|Nationwide Children's Hospital||Not yet recruiting|
|Columbus, Ohio, United States, 43205|
|United States, Texas|
|M.D. Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Rigshospitalet||Not yet recruiting|
|København, Denmark, 2100|
|Hospital Sant Joan de Déu||Not yet recruiting|
|Barcelona, Spain, 08010|
|Study Director:||Steen Lisby, MD||Y-mAbs Therapeutics|