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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03275402
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
Y-mAbs Therapeutics

Tracking Information
First Submitted Date  ICMJE September 6, 2017
First Posted Date  ICMJE September 7, 2017
Last Update Posted Date March 11, 2020
Actual Study Start Date  ICMJE December 11, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2018)
Overall survival rate [ Time Frame: 3 years ]
Overall survival rate at 3 years after the first treatment dose of 131I-omburtamab.
Original Primary Outcome Measures  ICMJE
 (submitted: September 6, 2017)
Overall survival [ Time Frame: 3 years ]
Overall survival at 3 years
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2018)
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2017)
  • Objective response rate [ Time Frame: 3 years ]
    To evaluate the objective response rate
  • CNS progression free survival [ Time Frame: 6 month ]
    To evaluate the CNS progression free survival
  • Dosimetry of 131I-burtomab [ Time Frame: 2 weeks ]
    To evaluate the dosimetry of 131I-burtomab
  • Safety data will be collected via adverse event (AE) and serious adverse event (SAE) reporting during the trial and graded according to CTCAE, version 4.0 [ Time Frame: 3 years ]
    Safety data will be collected via adverse event (AE) and serious adverse event (SAE) reporting during the trial and graded according to CTCAE, version 4.0
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases
Official Title  ICMJE A Multicenter Phase 2/3 Trial of the Efficacy and Safety of Intracerebroventricular Radioimmunotherapy Using 131I-omburtamab for Neuroblastoma Central Nervous System/Leptomeningeal Metastases
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 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE 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)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroblastoma
  • CNS Metastases
  • Leptomeningeal Metastases
Intervention  ICMJE Biological: 131I-omburtamab
Murine IgG1 monoclonal antibody radiolabeled with iodine-131
Other Name: 131I-8H9
Study Arms  ICMJE Experimental: 131I-omburtamab

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.

Intervention: Biological: 131I-omburtamab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 6, 2017)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joris Wilms +4570261414 clinicaltrials@ymabs.com
Listed Location Countries  ICMJE Denmark,   Spain,   United States
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT03275402
Other Study ID Numbers  ICMJE 101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Y-mAbs Therapeutics
Study Sponsor  ICMJE Y-mAbs Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Steen Lisby, MD Y-mAbs Therapeutics
PRS Account Y-mAbs Therapeutics
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP