Active — Not RecruitingPhase 1

Phase I Study of 131-I mIBG Followed by Nivolumab & Dinutuximab Beta Antibodies in Children With Relapsed/Refractory Neuroblastoma

United States, United Kingdom44 participantsStarted 2018-05-24

Plain-language summary

Neuroblastoma, the most common extra-cranial solid tumour in children, remains one of the major challenges in paediatric oncology. A promising way to further improve outcome in this disease appears to be the development of adjuvant therapeutic strategies. In this research the anti-GD2 antibody, which is a standard treatment, is to be combined with 131-l Metaiodobenzylguanidine (mlBG) and anti-Programmed Cell Death Protein 1 (anti-PD1) antibody Nivolumab - the investigated drugs - with the aim of generating sustained anti-neuroblastoma immunity. In particular it will be determined the safety and tolerability of the novel combination as well as documented any evidence of efficacy in paediatric patients with relapsed and refractory high risk neuroblastoma. This study is sponsored by the University Hospital Southampton and will take place in 4 hospitals in the United Kingdom, Germany and USA. The estimated duration of the study is 2 years, starting in December 2016. This is an "adaptive study". Such design uses accumulating of data from the ongoing trial to modify aspects of the study (e.g. duration, number of treatments) without undermining its validity or integrity. There will be 3 cohorts of patients. As safety of Nivolumab is well established, Cohort 1 will assess its safety and tolerability in combination with 131-l mlBG. Cohort 2 will then add anti-GD2 to the drug combination, assessing safety and tolerability. Cohort 3 will escalate all 3 agents to the full 100% dose level to assure safety for expanded analyses of clinical and laboratory data at that dose level. Patients will initially be recruited into Cohort 1. Patients must have completed at least 12 weeks of trial treatment without reaching a Dose Limiting Toxicity before a patient can be recruited to the next cohort. A minimum of 3 evaluable patients will be treated in cohorts 1-3. Assuming the full dose combination therapy (cohort) is tolerable, 15 evaluable patients will be treated.

Who can participate

Age range1 Year – 99 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * At study entry patients must be \> 1 year * Relapsed or refractory high risk neuroblastoma (as defined by International Neuroblastoma Risk Group (INRG) criteria) * MIBG avid disease on imaging within 4 weeks to study entry. * ≥ 3 months since any myeloablative chemotherapy / stem cell rescue * ≥ 42 days since any other immunotherapy e.g. tumour vaccines. At least 3 half lives since last dose of any monoclonal antibody therapy. * Patients must have a performance status greater or equal 60% (Lansky Score or Karnofsky) * Estimated life expectancy ≥ 12 weeks * Adequate bone marrow function: Absolute Neutrophil Count (ANC) \>1.0 x 10/L, platelets, 20 x 10/L and haemoglobin \> 8.0 g/dL. * Adequate renal function: serum creatinine \<1.5 mg/dL or a estimated creatinine clearance or radioisotope Glomerular Filtration Rate Study (GFR) of \> 60 mL/minute/1.73m2. * Adequate cardiac function: shortening fraction of 28 % by echocardiogram. * Adequate hepatic function: Alanine transaminase (ALT) or Aspartate transaminase (AST) \< 5 x ULN and a total bilirubin \< 1.5 x Upper Limit of Normal (ULN) * Adequate lung function: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) \>60% of the predicted by pulmonary function tests. Children unable to do Pulmonary Function Tests (PFTs) should have no dyspnea at rest and a pulse oximetry \>94% on room air. * Adequate pancreatic function: serum lipase \< 1.5 x upper limit normal * Patients may have had pri…

What they're measuring

Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] of 131-I-MIBG, ch14.18/CHO and Nivolumab in paediatric patients

Timeframe: 2 Years

Trial details

NCT IDNCT02914405

SponsorUniversity Hospital Southampton NHS Foundation Trust

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-06-30