Eligibility

Eligible Ages

Between 3 Years and 35 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

- 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.

- 123MIBG-avid lesion detected on 123MIBG 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: >= 1000/mcL

- Platelets: >= 100,000/mcL (transfusion-independent)

- 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.

- 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 does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial.

- Participants must not have >= grade 2 diarrhea at the time of entry.

- Participants who are unable to tolerate oral/nasogastric/gastrostomy medications
will not be eligible for this trial. Additionally, participants with significant
malabsorption will not be eligible for this trial.

- Participants must not have 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 are not
eligible.