New hope for kids with Tough-to-Treat neuroblastoma: experimental drug combo enters human testing

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

* ELIGIBILITY CRITERIA: * Disease Requirements: * Histologic diagnosis: Participants must have pathology-confirmed neuroblastoma (no time limit). Old reports and tissue blocks can be used if available. Confirmation of disease will be based on the review of pathology at the NIH any time before starting and is based on one of the following: (1) A confirmed pathological diagnosis made from tumor tissue by light microscopy (with or without immunohistology or electron microscopy), (2) the combination of bilateral bone marrow aspirate and trephine biopsy containing confirmed tumor cells (e.g., syncytia or immunocytologically positive clumps of cells) and increased levels of urinary catecholamine metabolites. * Active disease status: Participants must have relapsed and/or refractory disease after receiving frontline chemotherapy and at least one salvage treatment (can include dinutuximab, temozolomide, and/or irinotecan), with no alternative curative options. * Documentation of disease: Participants must have evaluable disease according to the International Neuroblastoma Response Criteria (INRC). This means they must have an area of active disease that can be identified by MIBG, PET, MRI/CT, or bone marrow studies. Participants must have at least ONE of the following at the time of enrollment: * Measurable tumors on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Measurable is defined as \>=10 mm in at least one dimension. * Either 123MIBG-avid lesion detected on 123MIBG scan with positive uptake at a minimum of one site or FDG-PET-avid lesion detected on FDG-PET scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction. * Participants with resistant/refractory soft tissue disease that is not 123MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo a biopsy to document the presence of viable neuroblastoma. Biopsy is not required for participants who have a new site of soft tissue disease (radiographic evidence of disease progression) regardless of whether progression occurs while receiving therapy or after completion of therapy. * Participants with bone marrow disease in at least one sample from bilateral bone marrow biopsies will be eligible (documented neuroblastoma cells). * Participants with a history of CNS disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment. * Prior Therapy: Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment. * Chemo-immunotherapy: Participants are eligible if they have received prior therapy with dinutuximab/temozolomide/irinotecan, even if they may not have responded previously * Myelosuppressive chemotherapy: Potential trial participants should have recovered from clinically significant myelosuppression. * Non-chemotherapy anti-neoplastic agents: With anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or ANC counts), sufficient time needs to have passed for the drug to have cleared the body. This is to prevent overlapping non-hematological toxicity. * Anti-GD2 antibody: toxicity related to prior antibody therapy must be recovered to grade \<=1. * Radiation therapy: Given the possible negative effect of radiation on bone marrow cells and count recovery after chemotherapy, potential trial participants should have recovered from clinically significant radiation-induced myelosuppression. Palliative radiation while on study is not permitted. * Stem cell transplants (SCT): After autologous stem cell transplants or stem cell infusions (including stem cell infusions given as supportive care following 131 I-MIBG therapy), all hematologic and other eligibility criteria must have been met. * 131I-MIBG therapy: After therapeutic 131 I-MIBG, all hematologic and other eligibility criteria must have been met. * Participants who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days before study enrollment are not eligible. -Age Requirement: * Age \>= 3 years and \<= 35 years at the time of enrollment. -Clinical Performance Status: * Participants \>= 16 years of age: Karnofsky \>= 50 percent; Participants \< 16 years of age: Lansky scale \>= 50 percent. Participants who are unable to walk because of paralysis, but who are upright in a wheelchair will be considered ambulatory to calculate the performance score. -Adequate Organ and Marrow Function as Defined Below: * Absolute neutrophil count: \>= 750/mcL (must be off of G-CSF for at least 1 week) * Platelets: \>= 75,000/mcL (transfusion-independent, unless patient has bone marrow disease in which case transfusions are permitted to reach this threshold) * Total bilirubin: \<=2 X ULN (except in the case of participants with documented Gilbert s disease \< 3x ULN) * AST(SGOT)/ALT(SGPT): \<=3 X institutional upper limit of normal * Creatinine: \<= the maximum for age listed in the table below OR * Measured creatinine clearance: \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above the max listed below per age: * Age (Years) \<=5, Maximum Serum Creatinine \<= 0.8 (mg/dL) * Age (Years) 6 to \<= 10, Maximum Serum Creatinine \<=1.0 (mg/dL) * Age (Years) \>10, Maximum Serum Creatinine \<= 1.2 (mg/dL) * Cardiac function: Left ventricular ejection fraction \>= 52 percent. * Pulmonary Function * Baseline oxygen saturation \>92 percent on room air at rest * Participants with respiratory symptoms clinically concerning for decreased pulmonary function must have a DLCO/adjusted \> 45 percent. For children who are unable to cooperate for PFTs, they must not have dyspnea at rest or a known requirement for supplemental oxygen. * Given the teratogenic effects of the therapy, participants of childbearing or child fathering potential must agree to be abstinent or use highly effective contraception (hormonal; intrauterine device; surgical sterilization). This restriction will be from the time of enrollment on this study and for four months (in persons who can father children) or six months (in participants who can bear children) after completing therapy. Participants may also confirm with their partners that they are using a highly effective method. * Participants who are nursing or plan to nurse must agree to discontinue/postpone nursing while on study therapy since it cannot be ruled out with certainty that any of the investigational drugs can be transmitted via breast milk. * Ability of participant or parents/legal guardian to understand and sign a written informed consent document. EXCLUSION CRITERIA: * Presence of pericardial effusion. * Chronic immunosuppression (physiologic steroid supplementation is allowed but any chronic immunosuppressant like steroids or other modulators are not allowed) * Major surgery within 4 weeks prior to initiation of study therapy * Current/active human immunodeficiency virus (HIV) infection, as measured by seropositivity for HIV antibody. * Current/active HBV/HCV infection as measured by seropositivity for Hepatitis C or positive for Hepatitis B surface antigen (HBsAg). * History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biological composition to irinotecan and temozolomide used in study. * Participants with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous. * Positive serum or urine beta-HCG pregnancy test performed at screening due to the teratogenic effects of chemotherapy. * Participants with a prior or concurrent malignancy whose natural history or treatment with the safety or efficacy assessment of the investigational regimen. * Participants with \>= grade 2 diarrhea at the time of entry. * Participants who are unable to tolerate oral/nasogastric/gastrostomy medications. Additionally, participants with significant malabsorption will not be eligible for this trial. * Participants with uncontrolled infection. * Participants with a history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy.