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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
Sponsor:
Information provided by (Responsible Party):
Y-mAbs Therapeutics

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 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)
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
Estimated Study Start Date : October 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
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.

Biological: 131I-omburtamab
Murine IgG1 monoclonal antibody radiolabeled with iodine-131
Other Name: 131I-8H9




Primary Outcome Measures :
  1. Overall survival rate [ Time Frame: 3 years ]
    Overall survival rate at 3 years after the first treatment dose of 131I-omburtamab.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 3 years ]
    Overall survival at 3 years after the first treatment dose of 131I-omburtamab.

  2. 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.

  3. 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.

  4. 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.

  5. Dosimetry of 131I-omburtamab [ Time Frame: 2 weeks ]
    Whole-body, organ, blood, and CSF radiation dosimetry.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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).



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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


Contacts
Contact: Joris Wilms +4570261414 clinicaltrials@ymabs.com

Locations
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
Denmark
Rigshospitalet Not yet recruiting
København, Denmark, 2100
Spain
Hospital Sant Joan de Déu Not yet recruiting
Barcelona, Spain, 08010
Sponsors and Collaborators
Y-mAbs Therapeutics
Investigators
Study Director: Steen Lisby, MD Y-mAbs Therapeutics

Responsible Party: Y-mAbs Therapeutics
ClinicalTrials.gov Identifier: NCT03275402     History of Changes
Other Study ID Numbers: 101
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Y-mAbs Therapeutics:
Radioimmunotherapy
Neuroblastoma
CNS Metastases
Leptomeningeal Metastases
Pediatric

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Neuroblastoma
Meningeal Carcinomatosis
Neoplastic Processes
Neoplasms
Pathologic Processes
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases