Treatment of pediatric neuroblastoma patients with CNS relapse as evidenced by CNS/LM metastases MedDRA version: 21.1 Level: PT Classification code 10073130 Term: Central nervous system neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: 131I-omburtamab
Product Code: 131I-murine 8H9
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: omburtamab
CAS Number: 1895083-75-6
Current Sponsor code: 131I-omburtamab
Sponsors
Y-mAbs Therapeutics A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have a histologically confirmed diagnosis of neuroblastmona with relapse in the CNS or LM. 2. Patients need to have progressed in CNS/LM through induction therapy or have relapsed in CNS/LM following induction. CNS/LM progression/ relapse is defined as LM disease or metastatic deposits in the CNS parenchyma, (excluding skull bone-based metastases) 3. Stable systemic disease not requiring chemo/ immunotherapy as judged by the investigator 4. Ventriculoperitoneal (VP) shunts (only shunts with programmable valves can be accepted) is allowed however should be closed (or adjusted to highest pressure setting) during Investigational Medicinal Product (IMP) infusion. It is recommended that the VP shunt remains closed for approximately 5 hours after treatment and then readjusted. The shunt readjustment times are at the discretion of the treating physician. Closure of VP shunt is done at the discretion of the treating physician and the VP shunt should at any time based on patient safety evaluation be reopened at the assessment of the treating physician. Patients with ventriculo-atrial or ventriculo-pleural shunts are not eligible. 5. Patients must be between the ages of birth and 18 years at the time of screening 6. Patients must have a life expectancy of at least 3 months as judged by the investigator. 7. Acceptable hematological status defined as: • Hemoglobin =8 g/dL • White blood cell count =1000/µL • Absolute neutrophil count =500/µL • Platelet count =50,000/µL 8. Acceptable liver function defined as: • (ALT) and /or AST = 5 times UNL • Bilirubin =3 x UNL In case either AST or ALT =3 x ULN, bilirubin must be = 2 UNL 9. Acceptable kidney function defined as: • eGFR >60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation (Appendix 3). 10. Written informed consent from legal guardian(s) and/or child must be obtained in accordance with local regulations. Pediatric patients must provide assent as required by local regulations Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with primary neuroblastoma (NB) in CNS 2. Patients must not have obstructive or symptomatic communicating hydrocephalus. 3. Patients must not have worsening of neurologic function, according to the assessment by investigator, within 3 weeks prior to first dose of 131I-omburtamab. 4. Patients must not have an uncontrolled life-threatening infection. 5. Patients must not have received cranial or spinal irradiation less than 3 weeks prior to first dose of 131I-omburtamab in this trial 6. Patients must not have received systemic chemo/ immunotherapy (corticosteroids not included) less than 3 weeks prior to enrolment in this trial. 7. Patients must not have received any B7-H3 treatment prior to enrolment in this trial. 8. 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 enrolment 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. 9. Patients must not be pregnant or breast-feeding 10. Female patients of child-bearing potential (i.e. having experienced menarche) and male partners to female patients who do not agree to the use of effective contraception during treatment and for a period of 12 months after the last 131I-omburtamab dose. Effective contraception for women is defined as intrauterine devices or hormonal contraceptives(contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release). Effective contraception for male partners is defined as use of condoms. To be exempt from the requirement to use contraception after 131I-omburtamab treatment, one of the criteria described in section 9.2.11 of this protocol must be met. 11. Fertile male patients who do not agree to the use of condoms during treatment and for a period of 12 months after the last 131I-omburtamab dose. For a sterilized male patient to be exempt from the requirement to use contraception after 131I-omburtamab treatment, he must have undergone surgical sterilization (vasectomy).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate overall survival (OS) rate at 3 years;Secondary Objective: 1. To evaluate CNS/LM progression-free survival (CNS/LM PFS) at 6 and 12 months 2. To evaluate Overall Survival (OS) at 12 months 3. To evaluate the objective response rate (ORR) at 6 months 4. To evaluate dosimetry of 131I-omburtamab 5. To evaluate the pharmacokinetics of 131I-omburtamab 6. To evaluate safety of 131I-omburtamab 7. To evaluate the immunogenicity of 131I-omburtamab;Primary end point(s): Overall survival (OS) rate at 3 years after the first treatment dose of 131I-omburtamab;Timepoint(s) of evaluation of this end point: Up to 3 years after 131I-omburtamab treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. CNS/LM PFS at 6 and 12 months 2. OS at 12 months 3. ORR assessed as a combination of partial response and complete response as defined by the Response Assessment in Neuro-Oncology (RANO) group criteria for brain metastasis (Lin et al, 2015) or leptomeningeal metastases as defined by EANO-ESMO criteria (Le Rhun et al, 2017). ORR will be assessed at 6 months after the first treatment dose of 131Iomburtamab. 4. ORR according to CSF cytology. Response is defined as a complete response when CSF converts from positive at baseline to negative after treatment with 131I-omburtamab. 5. Whole-body, organ, blood, and CSF radiation dosimetry. 6. Pharmacokinetic analysis of activity in blood and CSF including derivation of best-fit uptake and/or clearance parameters (half-times, maximum value) of time-activity concentration curves and of I-131 residence times (i.e., cumulated activity) concentrations (in µCi-h/g). 7. 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. 8. Performance assessment to monitor gross changes in neurological function is performed at week 26 and subsequently every 6 months during trial period. 9. The rate of ADA occurrence assessed three weeks after the first and second treatment dose of 131I-omburtamab;Timepoint(s) of evaluation of this end point: Short-term follow-up at 26 weeks after treatment and with long-term follow-up for up to 3 years following treatment | — |
Countries
Canada, Denmark, Germany, Spain, United Kingdom, United States
Contacts
Public ContactVice President, Clinical
KLIFO A/S
Outcome results
None listed