Rapid Infusion of Dinutuximab with Chemotherapy for the Treatment of Relapsed, Refractory or Persistent High Risk Neuroblastoma or Ganglioneuroblastoma

Inclusion Criteria

• Patients ≥ 12 months of age at the time of enrollment are eligible for this study
• 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 at based on Children's Oncology Group (COG) risk classification. There are no requirements for minimal sites of disease for this study
• Prior Therapy (all dates below apply from time of enrollment) * Must have completed high-risk Induction therapy with at least 4 cycles of chemotherapy. * Myelosuppressive chemotherapy: At least 14 days must have elapsed since completion of myelosuppressive therapy. * Study specific limitations on prior therapy: Patients must have received previous treatment with dinutuximab (with or without chemotherapy). * Biologic (anti-neoplastic agents): Anti-cancer agents not known to be myelosuppressive (e.g. not associated with substantially reduced platelet or absolute neutrophil count [ANC] counts) are permitted while on study with principal investigator (PI) approval. However, they must be held during protocol therapy. The anti-cancer agent may be resumed after completion of final dinutuximab day in each cycle per physician discretion. ** Monoclonal antibodies: 7 days or 3 half lives must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1. ** Cellular Therapy (ie modified T-cells, natural killer [NK] cells, dendritic cells, etc.): 21 days must have elapsed and all associated toxicities recovered. ** Immunoglobulins: Intravenous Immunoglobulin (IVIG) should not be given within 14 days of starting dinutuximab treatment and 1 week after completing dinutuximab therapy. ** Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment. 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. Patients on any other immunosuppressive medications (e.g. cyclosporine, tacrolimus) are not eligible. * Radiation (XRT): Radiation may be given up to 7 days prior to enrollment if clinically indicated. Palliative radiation while on study is permitted but not during infusion days. * Stem Cell Transplants (SCT): Stem cell transplant may have been given at least 42 days prior to enrollment as long as hematologic and other eligibility criteria have been met to enroll. Patients who received autologous stem cell infusion to support nonmyeloablative 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 42 days after therapeutic 131I-MIBG provided that all other eligibility criteria are met. * Prior or planned concomitant treatment with eculizumab is permitted (e.g., treatment of Transplant-Associated Thrombotic Microangiopathy [TA-TMA]).
• 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 may given up to 14 days prior to enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70mL/min/1.73m^2 or a serum creatinine based on age/gender as follows: * 1 to < 2 years: Maximum serum creatinine 0.6 mg/dL (female), 0.6 mg/dL (male) * 2 to < 6 years: Maximum serum creatinine 0.8 mg/dL (female), 0.8 mg/dL (male) * 6 to < 10 years: Maximum serum creatinine 1 mg/dL (female), 1 mg/dL (male) * 10 to < 13 years: Maximum serum creatinine 1.2 mg/dL (female), 1.2 mg/dL (male) * 13 to < 16 years: Maximum serum creatinine 1.4 mg/dL (female), 1.5 mg/dL (male) * >= 16 years: Maximum serum creatinine 1.4 mg/dL (female),1.7 mg/dL (male) * 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
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 5.0 x ULN for age (≤ 225 U/L). For the purpose of this study, the ULN for SGPT is 45U/L
• Patients with a history of central nervous system (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
• Shortening fraction of ≥ 27% by echocardiography (ECHO), or ejection fraction of ≥ 50% by ECHO or gated radionuclide study
• 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 (PFTs) 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. Based on the established teratogenic potential of alkylating agents, pregnant women will be excluded from this study. Because of potential risks to breastfed infants due to drug metabolites that could be excreted in breast milk, female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study. Females of childbearing potential 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. Child-bearing potential is defined as all females ≥ 10 years of age and /or post-menarchal
• REGIMEN A: Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible
• REGIMEN A: Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment are not eligible
• REGIMEN A: 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 (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria are not eligible