Inclusion Criteria:
* Age: Patients ≥ 12 months of age at the time of enrollment are eligible for this study.
* Diagnosis: Patients must have a diagnosis of relapsed , refractory (defined as achieving less than a partial response), or persistent high-risk neuroblastoma or ganglioneuroblastoma (nodular) \[verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites at the time of diagnosis\] and have been designated as having high-risk disease based on COG risk classification.
No minimal sites of disease are required for this study.
Prior Therapy (all time-frames below apply from time of enrollment):
* Must have completed high-risk Induction therapy with at least 4 cycles of chemotherapy.
* At least 14 days must have elapsed since completion of myelosuppressive therapy.
* Patients must have received previous treatment with dinutuximab (with or without chemotherapy) within 2 months prior to enrollment without any dose-modifications
* Anti-cancer agents not known to be myelosuppressive (e.g. not associated with substantially reduced platelet or ANC counts) are permitted while on study with PI approval and must be held during dinutuximab therapy and may be resumed after completion of final dinutuximab day in each cycle per physician discretion.
* Monoclonal antibodies: ≥ 7days ( 3 half-lives) from infusion of last dose of antibody and all related toxicity must have resolved to Grade ≤ 1.
* Immunoglobulins: IVIG should not be given within 2 weeks of starting dinutuximab treatment or 1 week after completing dinutuximab therapy.
* Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment and must not require ongoing pharmacologic doses of systemic corticosteroids during protocol therapy.
* Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. (The only exception is for patients known to require 2mg/kg or less of hydrocortisone, or an equivalent dose of an alternative corticosteroid, as premedication for blood product administration in order to avoid allergic transfusion reactions). The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency.
* Radiation may be given up to 7days prior to enrollment if clinically indicated. Palliative radiation while on study is permitted except during dinutuximab infusion days.
* Stem cell transplant must be ≥ 6months prior to enrollment. Patients who received autologous stem cell infusion to support non-myeloablative therapy (such as 131 I-MIBG) are eligible at any time as long as they meet the other criteria for eligibility.
* 131I-MIBG therapy: Patients are eligible ≥6 weeks after therapeutic 131I-MIBG provided that all other eligibility criteria are met.
Adequate Bone Marrow Function Defined As:
* Peripheral absolute neutrophil count (ANC) ≥750/microL
* Platelet count ≥50,000/mL (transfusion independent for prior 7 days). Exemptions may be granted for patient specific criteria (i.e. low platelet function due to history of extensive prior therapy or bone marrow disease)
* Hematologic growth factor (ie GM-CSF, GCSF or bioequivalent) may given up to 14 days prior to enrollment Note: concurrent use of platelet directed growth factor is permitted
Adequate Renal Function Defined As:
* Creatinine clearance or radioisotope GFR ≥70mL/min/1.73m2 or
* Adequate serum creatinine based on age/gender
Note: Patients with history of transplant-associated thrombotic microangiopathy (TA-TMA) must have a creatinine clearance or radioisotope GFR at baseline to assess renal function and must meet the above criteria.
Adequate Liver Function Defined As:
* Total bilirubin ≤1.5 x ULN for age AND
* SGPT (ALT) ≤ 5.0 x ULN for age (≤ 225 U/L). For the purpose of this study, the ULN for SGPT is 45U/L.
Adequate Central Nervous System Function Defined As:
* Patients with a history of CNS disease must have no clinical evidence of active progressive CNS disease at the time of study enrollment. Patients with history of CNS disease need to have at least stable tumor in the CNS for at least one month.
* Patients with seizure disorders may be enrolled if seizures are well controlled on antiepileptic medication
* CNS toxicity ≤ Grade 2
Adequate Cardiac Function Defined As:
* Shortening fraction of ≥27% by ECHO, or
* Ejection fraction of ≥50% by ECHO or gated radionuclide study.
Adequate Pulmonary Function Defined As: No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry \>94% if there is a clinical indication for pulse oximetry. For patients who do not have respiratory symptoms, full pulmonary function tests are NOT required.
Exclusion Criteria:
* Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study.
* Females of childbearing potential (≥ 10 years of age and /or post-menarchal) must have a negative pregnancy test to be eligible for this study, and they must agree to use 2 acceptable methods of contraception or abstain from heterosexual intercourse while participating in this study.
* Pregnant women will be excluded from this study.
* Female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study.
* Patients with uncontrolled hypertension are not eligible; uncontrolled hypertension is defined as sustained hypertension not well-controlled on blood pressure medication(s).
* If enrolling on Regimen A (temodar, irinotecan, dinutuximab arm only): patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible. Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment are not eligible. Patients must not have ≥ Grade 2 diarrhea
* Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma.
* Patients must not have uncontrolled infection.
* Patients with a history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy are not eligible.
* Patients who could not tolerate standard dose of dinutuximab infusion in 20 hour or less are not eligible.
* Patients with a significant intercurrent illness or disease of any major organ system that would impair their ability to withstand protocol therapy are not eligible
