Feasibility Study of Prolonged Administration of Naxitamab, Irinotecan, and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma

Inclusion Criteria: * Histologic Diagnosis: Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines \[i.e. \> 2 x upper limit of normal (ULN)\], at the time of initial diagnosis. * Relapsed or Refractory Disease Patients must have ONE of the following: * 1\) Any prior episode of recurrent high-risk disease following completion of frontline high-risk therapy. Patients may have received other lines of therapy for treatment of recurrent disease prior to enrolling to this trial. * 2\) Prior progressive high-risk disease during frontline high-risk therapy. Patients may have received other lines of therapy for treatment of progressive disease prior to enrolling to this trial. * 3\) Primary resistant/refractory disease (less than partial response by INRC) detected after the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, ANBL2131) that was treated with additional therapy with the goal of improving remission status prior to enrolling to this trial. * Documentation of Disease: Patients must have at least ONE of the following at the time of enrollment: * 1\) Measurable tumor on MRI or CT scan. Measurable is defined as ≥ 10 mm in at least one dimension (or 15 mm in short axis for lymph node) on spiral/helical CT or MRI that is MIBG avid or demonstrates increased FDG uptake on PET scan. * 2\) MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one site. This site must represent disease recurrence or known refractory disease at a site not previously radiated. * 3\) In patients with known MIBG non-avid disease, FDG-avid lesion detected on FDG- PET scan with positive uptake at a minimum of one site. This site must represent disease recurrence or known refractory disease at a site not previously radiated. * Of note, patients with isolated bone marrow only disease are NOT eligible for this trial. * Prior Therapy: Prior lines of anticancer therapy allowed as described in eligibility section above by disease status. Washout periods from prior therapy are as follows: * Myelosuppressive chemotherapy: Last dose given 14 days prior to enrollment. * Small molecule targeted therapies (anti-neoplastic agents including retinoids): Last dose given 7 days prior to enrollment. * Monoclonal antibodies: Last given at least 7 days or 3 half-lives, whichever is longer, prior to enrollment. * Radiation: * Craniospinal irradiation: Last fraction received minimum of six weeks prior to enrollment * All other radiation: Last fraction received minimum of 14 days prior to enrollment * Hematopoietic stem cell transplant: Date of autologous stem cell infusion following myeloablative chemotherapy must have been a minimum of 12 weeks prior to enrollment. Patients are not eligible post allogeneic stem cell transplant. * Cellular therapies (including CAR-T cells, NK cells, other related cellular therapies): 21 days from the last cellular therapy infusion prior to enrollment and recovery from all associated toxicities * 131I-MIBG therapy: Last therapy received a minimum of 6 weeks prior to enrollment. * Age: Patients 1 - 30 years of age at the time of enrollment are eligible for this study. * Performance level: Patients must demonstrate adequate performance level as measured by Karnofsky ≥ 70% for patients aged 16 years or older, OR Lansky ≥ 70% for patients younger than 16 years. Please see Appendix A for performance score measurement. * Participants must meet the following organ and marrow function as defined below: * Adequate bone marrow function as defined as BOTH of the following: * Peripheral absolute neutrophil count (ANC) ≥ 750/uL. Must be more than 14 days from last administration of long-acting myeloid stimulating factor (e.g. pegfilgrastim) or 7 days from last administration of short- acting myeloid stimulating factor (e.g. filgrastim or sargramostim) * Peripheral platelet count ≥ 75,000/uL. Must be without support, defined as at least 7 days from last platelet transfusion and/or platelet stimulating agent. * Adequate renal function as defined as EITHER of the following: * Radioisotope GFR ≥ 70ml/min/1.73 m2 * Serum creatinine based on age/sex as follows: * Age Maximum Serum Creatinine (mg/dL) * 1 to \< 2 years Male 0.6 Female 0.6 * 2 to \< 6 years Male 0.8 Female 0.8 * 6 to \< 12 years Male 1.0 Female 1.0 * 12 to \< 13 years Male 1.2 Female 1.2 * 13 to \< 16 years Male 1.5 Female 1.4 ---≥ 16 years Male 1.7 Female 1.4 * The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR. * Adequate liver function defined as ALL of the following: * Total bilirubin ≤ 1.5 x ULN for age\* * ALT ≤ 3.0 x ULN for age (≤ 135 U/L). For the purpose of this study, the ULN for ALT is 45 U/L * Albumin \> 3 g/dL --\*If patient has known Gilbert syndrome, direct bilirubin should be used to measure liver function instead of total bilirubin. Direct bilirubin must be within normal limits for age for these patients. * Adequate cardiac function measured by echocardiogram as defined as EITHER of the following: * Shortening fraction of ≥ 27% * Ejection fraction of ≥ 50% * Adequate blood pressure as defined by BOTH of the following: * Patients must have \< Grade 2 hypertension AND * Be on no more than one standing antihypertensive * Adequate pulmonary function: Patients must have adequate pulmonary function, defined as: * No dyspnea at rest * No exercise intolerance * Room air O2 saturation \>94% * Not on chronic oxygen therapy * Adequate pancreatic function, defined as lipase \< 1.5 x ULN * Able to comply with protocol requirements * Adequate contraception: The effects of naxitamab on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, participants with potential to become pregnant or to impregnate a partner must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a participant become pregnant or suspect they are pregnant while they or their partner is participating in this study, they should inform the treating physician immediately. Patients treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of protocol therapy. * Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document. Exclusion Criteria: * Chronic (more than 2 weeks duration) diarrhea \> grade 1 * Prior receipt of naxitamab * Untreated central nervous system (CNS) metastatic disease * Pregnant or currently breast feeding: Pregnant participants are excluded from this study because protocol therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the parent with protocol therapy, participants planning to continue breastfeeding are excluded from the study. * Clinically significant arrhythmias, i.e. those that cause clinical symptoms or require medications for control of symptoms * Prior allergic reaction to irinotecan or temozolomide * Discontinuation of prior irinotecan or temozolomide due to unacceptable toxicity * Discontinuation of prior GD2 directed immunotherapy due to unacceptable toxicity other than allergic reaction * Serious intercurrent illness * Active uncontrolled infection * Existing major organ dysfunction CTCAE \>Grade 2, except for hearing loss and hematological status, kidney, and liver function as described in eligibility criteria * Concomitant Medication Restrictions: * Patients may not be receiving immunosuppressive medications including pharmacologic doses of glucocorticoids or immunomodulatory agents due to concern for inhibition of antibody effect. Local and inhaled steroid agents are permitted. * Patients may not be receiving concurrent anti-cancer agents or radiotherapy. * Patients may not have received valproic acid within 14 days prior to enrollment. * Patients may not have received strong CYP3A4 inducers, strong CYP3A4 inhibitors, or strong UGT1A1 inhibitors within 14 days prior to enrollment. * Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.