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Fachinformation

JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03275402

Studienbeginn:
Dezember 2018

Letztes Update:
29.09.2020

Wirkstoff:
131I-omburtamab

Indikation (Clinical Trials):
Neoplasm Metastasis, Neoplasms, Second Primary, Neuroblastoma, Meningeal Carcinomatosis

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
-

Sponsor:
Y-mAbs Therapeutics

Collaborator:
-

Studienleiter

Agon Hyseni, MD
Study Director
Y-mAbs Therapeutics

Kontakt

Studienlocations (3 von 12)

Childrens Hospital Los Angeles
90027 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
University of Florida
32611 Gainesville
United StatesRekrutierend» Google-Maps
Riley Hospital for Children
46202 Indianapolis
United StatesRekrutierend» Google-Maps
Memorial Sloan Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
Nationwide Children's Hospital
43205 Columbus
United StatesAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Overall survival rate (Time Frame - 3 years):
Overall survival rate at 3 years after the first treatment dose of 131I-omburtamab.



Secondary outcome:

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).

Geprüfte Regime

  • 131I-omburtamab (131I-8H9):
    Murine IgG1 monoclonal antibody radiolabeled with iodine-131

Quelle: ClinicalTrials.gov


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