A Phase I study of 131-I mIBG followed by Nivolumab and Dinutuximab beta Antibodies in children with relapsed/refractory Neuroblastoma.

Phase 1

• Conditions: Relapsed or refractory high risk neuroblastoma; MedDRA version: 20.0Level: PTClassification code 10029260Term: NeuroblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002221-11-DE
• Lead Sponsor: niversity Hospital Southampton NHS Foundation Trust (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-02-01
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1 Relapsed or refractory high risk neuroblastoma (as defined by INRG criteria)
2 MIBG avid disease on imaging within 4 weeks prior to study registration .
3 Performance status = 60%, estimated life expectancy = 12 weeks
4 Adequate renal, cardiac and hepatic function.
5 Patients with CNS metastasis may be included provided that CNS disease has been previously treated and has been stable for 4 weeks prior to study entry
6 At least 1 x 106 /Kg CD34 autologous stem cells stored and available if needed
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
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 who have previously received ch14.18 (CHO or SP2/0) and have had severe or life threatening toxicity necessitating withdrawal of treatment previously
2. Co-existent autoimmune disease
3. Patients receiving corticosteroids (other than physiological replacement) or other chronic immunosuppressive agents.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the safety and tolerability of the novel combination of 131-I-MIBG, Dinutuximab beta and Nivolumab in paediatric and young adult patients.;Secondary Objective: - To document any evidence of efficacy of 131-I-MIBG, Dinutuximab beta and Nivolumab in patients with relapsed and refractory high risk neuroblastoma (time to progression, objective response rate)<br>- To analyse FcR and KIR/KIR ligand genotypes and correlate with objective response rate / time to progression<br>- To determine base line and end of infusion concentration of Dinutuximab beta in cycles 1, 3 and 5<br>- To determine HACA response to Dinutuximab beta (prior to cycle 1 and after cycle 5);Primary end point(s): Incidence, severity (according to CTCAE V5) and causality of adverse events;Timepoint(s) of evaluation of this end point: Collection of adverse events should begin from enrolment on the study, and continue until 100 days after the last dose of study treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Tumour responses: proportion of evaluable subjects with a best objective response of PR or better and time to progression<br>• FcR and KIR/KIR ligand genotype<br>• Anti-ch14.18/CHO (Dinutuximab beta) HACA<br>• Serum concentration Dinutuximab beta;Timepoint(s) of evaluation of this end point: • Tumour responses:<br>• FcR and KIR/KIR ligand genotype<br>• Anti-ch14.18/CHO (Dinutuximab beta) HACA<br>• Serum concentration Dinutuximab beta: base line and end of infusion, cycles 1, 3 and 5