A clinical trial in several sites where pediatric patients with Neuroblastomaare treated with injections of 131I-burtomab (the study drug). Thetolerability and efficacy of the drug will be tested.

Phase 1

Conditions: Treatment of pediatric neuroblastoma patients with CNS relapse asevidenced by CNS/LM metastases
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-001828-22-GB

Lead Sponsor: Y-mAbs Therapeutics A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 32

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: 32
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

1. Patients with primary neuroblastoma (NB) in CNS
2. Patients must not have obstructive or symptomatic communicating
hydrocephalus as determined by Ommaya patency/CSF flow study.
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 131Iomburtamab
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).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: 1. To evaluate CNS/LM progression-free survival (CNS/LM PFS) at 6 and<br>12 months.<br>2. To evaluate Overall Survival (OS) at 12 months.<br>3. To evaluate the objective response rate (ORR) at 6 months.<br>4. To evaluate dosimetry of 131I-omburtamab<br>5. To evaluate the pharmacokinetics of 131I-omburtamab<br>6. To evaluate safety of 131I-omburtamab<br>7. To evaluate the immunogenicity of 131I-omburtamab.;Main Objective: To evaluate overall survival (OS) rate at 3 years;Primary end point(s): Overall survival (OS) rate at 3 years after the first treatment dose of<br>131I-omburtamab;Timepoint(s) of evaluation of this end point: Up to 3 years after 131I-omburtamab treatment

Secondary Outcome Measures

Name	Time	Method

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