A Study Of Naxitamab , Granulocyte Macrophage Colony Stimulating Factor For Patients With Relapsed /Refractory , Soft Tissue or Anti GD2 Immunotherapy Refractory Neuroblastoma

Inclusion Criteria:

1. Diagnosis of neuroblastoma (NB) as defined per INRC as

   1. histopathology of tumor biopsy, or
   2. BM aspirate or biopsy indicative of NB by histology plus high blood or urine catecholamine metabolite levels or MYCN amplification, or
   3. Fluorodeoxyglucose (FDG), MIBG avid lesion(s)
2. High-risk NB as defined as any of the following:

   1. Stage 4 with MYCN amplification
   2. Stage 4 without MYC amplification \>1.5 y of age
   3. Stage 3 with MYCN amplification
3. Relapsed/refractory Neuroblastoma with

   1. Evidence of soft tissue disease or
   2. Progessive disease/incomplete response/relapsed to previous treatment with Naxitamab plus GM-CSF
4. Prior treatment with murine and hu3F8 is allowed
5. Prior treatment with irinotecan or temozolomide or ICE is permitted
6. Evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy
7. Age ≥18 months
8. Acceptable hematological status defined as:

   1. Hemoglobin ≥8 g/dL (5.0 mmol/L)
   2. White blood cell count ≥1000/μL
   3. Absolute Neutrophil Count (ANC) ≥500/μL
   4. Platelet count ≥50,000/μL
9. Acceptable liver function defined as:

   1. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 times Upper Limit of Normal (ULN)
   2. Bilirubin ≤1.5 x ULN
10. Acceptable kidney function defined as:

    a. estimated Glomerular Filtration Rate (eGFR) \>60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation
11. Written informed consent from legal guardian(s) and/or patient in accordance with local regulations. Children must provide assent as required by local regulations (≥ 12 years old).

Exclusion Criteria:

1. Existing major organ dysfunction \> grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of WBCs, RBCs, and platelets).
2. Active life-threatening infection.
3. Pregnant women or women who are breast-feeding.
4. Inability to comply with protocol requirements, including genetic studies.
5. History of allergy to GM-CSF ≥ G4 (Common Terminology Criteria for Adverse Events- CTCAE) or does not respond to treatment.
6. Absolute Neutrophil Count (ANC) \< 500/uL .
7. Platelet count \<50,000/uL.
8. Patients with relapsed/refractory Neuroblastoma with solely bone marrow/bone involvement. Only patients with B/BM compartiment disease who show progressive disease/incomplete response/relapsed to previous treatment with Naxitamab plus GM-CSF may be eligible (inclusion critèrium #3).