• Patients must be ≥ 1 year of age

• Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low- or intermediate-risk, but then reclassified as high-risk are also eligible.

• Patients must have a previously histologically confirmed diagnosis of neuroblastoma:

∙ That is recurrent/relapsed or refractory/persistent according to INRC (see Section 21.1) AND

‣ For which standard curative measures do not exist or are no longer effective.

‣ patients at first relapse are eligible as no known curative therapies exist for relapsed high-risk neuroblastoma.

• Patients must have evaluable or measurable disease at enrollment.

• In addition, patient must have experienced at least one of the following:

• a. New disease site documented on at least one of the following: i. 123I-meta-iodobenzylguanidine (MIBG) or 18F-mFBG (meta-fluorobenzylguanidine) scan; OR ii. CT/MRI; OR iii. FDG or Ga-68 Dotatate PET (in patients known to have MIBG non-avid tumor) and MRI findings consistent with tumor (i.e., bone lesions), OR iv. Biopsy confirmed neuroblastoma for any new or progressing lesion. b. Greater than 20% increase in a least one dimension of soft tissue mass documented by CT/MRI and a minimum absolute increase of 5 mm in longest dimension in existing lesion(s). Previously irradiated lesions may be included.

• c. Bone marrow biopsy shows progressive disease according to the revised INRC (refer to Table 17) d. Stable persistent disease, such that response at the completion of upfront therapy or salvage therapy is less than partial response AND has a biopsy of at least one site showing viable neuroblastoma.

• e. Responding persistent disease, defined as at least a partial response to frontline therapy (i.e., at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT/MRI, or bone marrow aspirations/biopsies). Patients in this category are required to have histologic confirmation of viable neuroblastoma from at least one residual site (tumor seen on routine bone marrow morphology is sufficient).

• Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60 (See Table 13)

• Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age.

• Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease)

• Aspartate aminotransferase (AST) ≤ 2.5 ULN (exception: AST ≤ 5 x ULN for patients with liver metastases).

⁃ Alanine aminotransferase (ALT) ≤ 2.5 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).

⁃ Patients must have a baseline pulse oximetry of at least 92% on room air. In addition, a DLCO ≥ 60% (corrected for anemia) is required if PFTs are clinically appropriate as determined by the treating investigator.

⁃ Left ventricular shortening fraction (LVSF) ≥28% or ejection fraction (LVEF) ≥ 50% confirmed by Echo, or adequate ventricular function documented by a scan or a cardiologist.

• Patient age ≥ 6 months.

• Patients must have metastatic retinoblastoma according to International Retinoblastoma Staging System (IRSS) risk classification (4) at the time of study enrollment:

• a. Retinoblastoma Cohort 1 (Extra-CNS metastasis) i. Stage IVa disease ii. Extra-CNS disease must be confirmed as retinoblastoma by histology (either at diagnosis or recurrence) iii. Measurable disease: Defined as \> 1cm2 or biopsy-proven bone marrow disease iv. Prior treatment: Recurrent or refractory disease following treatment with COG ARET0321-like or equivalent regimen as part of upfront or recurrent therapy b. Retinoblastoma Cohort 2 (CNS disease) i. Stage IVb disease ii. Histologic confirmation is not required iii. CNS disease defined as measurable disease \>1cm2, non-measurable, or CSF positivity alone c. Prior treatment: i. Stage IVb.1 and IVb.2: Recurrent after treatment with COG ARET0321-like or equivalent regimen as part of upfront or recurrent therapy (see appendix 21.2) i. Stage IVb.3: Prior treatment is not required (i.e., eligible at initial diagnosis or recurrence) (see appendix 21.2)

• Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60 (See Table 13)

• Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN .

• Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease)

• Aspartate aminotransferase (AST) ≤ 2.5 ULN (exception: AST ≤ 5 x ULN for patients with liver metastases).

• Alanine aminotransferase (ALT) ≤ 2.5 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).

• Patients must have a baseline pulse oximetry of at least 92% on room air. In addition, a DLCO ≥ 60% (corrected for anemia) is required if PFTs are clinically appropriate as determined by the treating investigator.

• Left ventricular shortening fraction (LVSF) ≥28% or ejection fraction (LVEF) ≥ 50% confirmed by Echo, or adequate ventricular function documented by a scan or a cardiologist.