Clinical Trial Finder

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.

• - 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.

• - Adequate pancreatic function: serum lipase < 1.5 x upper limit normal.

• - Patients may have had prior Central Nervous System (CNS) metastasis at point of entry to study, but patients with mIBG avid parenchymal brain lesions will be excluded.

• - Patients must consent to the placement of a central venous line, if one has not already been placed.

• - Patients must have no immediate requirements for palliative chemotherapy, radiotherapy or surgery.

• - Females of childbearing potential must have a negative pregnancy test.

• - Patients with seizure disorders may be enrolled if seizures are well controlled.

• - All patients and/or their parents or legal guardians must sign a written informed consent.

• - All institutional and national requirements for clinical trials must be met.

• - Expression of PD-L1 by tumour is not a pre-requisite.

• - Parents or carers willing and able to comply with radiation safety measures needed for 131-I mIBG administration.

• - Patient must be judged capable of tolerating isolation procedures associated with 131-I-mIBG therapy.

• - Patients who have previously received ch14.18 (CHO or SP2/0) will not be excluded unless they have had severe or life threatening toxicity necessitating withdrawal of treatment previously or if they have a strong/neutralizing Human Antichimeric Antibody (HACA) (≥ 10 μg/ml) - Patients who have had previous 131-I mIBG therapy will not be excluded.

• - Patients previously treated with Nivolumab or any other PD-1 or PD-L1 targeting antibodies will be excluded from the study.

• - Previous allogeneic stem cell transplant or solid organ transplant.

• - Patients should be excluded if they have an active, known or suspected autoimmune disease.

• - Patients receiving systemic corticosteroids (other than physiological replacement) or other immunosuppressive agents within 14 days prior to study entry.

• - Unable to maintain platelets ≥ 50 x 109/l without transfusion.

• - HIV or Hepatitis B or C infection.

• - Patients with significant intercurrent illnesses and/or any of the following: - Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance.

• - Patients with significant psychiatric disabilities or uncontrolled seizure disorders.

• - Patients with active infections.

• - Patients with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade >2) are ineligible.

• - Patients with clinically significant, symptomatic, pleural effusions.

• - Patients who require, or are likely to require, corticosteroid or other immunosuppressive drugs.

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Interventions