Treatment With Dinutuximab, Sargramostim (GM-CSF), and Isotretinoin in Combination With Irinotecan and Temozolomide After Intensive Therapy for People With High-Risk Neuroblastoma (NBL)

This phase II trial studies if dinutuximab, GM-CSF, isotretinoin in combination with irinotecan, and temozolomide (chemo-immunotherapy) can be given safely to patients with high-risk neuroblastoma after Consolidation therapy (which usually consists of two autologous stem cell transplants and radiation) who have not experienced worsening or recurrence of their disease. Dinutuximab represents a kind of cancer therapy called immunotherapy. Unlike chemotherapy and radiation, dinutuximab targets the cancer cells without destroying nearby healthy cells. Sargramostim helps the body produce normal infection-fighting white blood cells. Isotretinoin helps the neuroblastoma cells become more mature. These 3 drugs (standard immunotherapy) are already given to patients with high-risk neuroblastoma after Consolidation because they have been proven to be beneficial in this setting. Chemotherapy drugs, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. They may also affect how well immunotherapy works on neuroblastoma cells. Giving chemo-immunotherapy after intensive therapy may work better in treating patients with high-risk neuroblastoma compared to standard immunotherapy.

PRIMARY OBJECTIVE:

I. To determine the feasibility of administering dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the frontline Post-Consolidation setting in patients with high-risk neuroblastoma who have undergone Induction and Consolidation therapy with tandem high-dose chemotherapy with stem cell rescue (ASCT).

SECONDARY OBJECTIVES:

I. To describe the toxicity profile of dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the Post-Consolidation setting.

II. To describe the event-free survival and overall survival of patients who receive dinutuximab in combination with irinotecan and temozolomide, GM-CSF, and isotretinoin in the Post-Consolidation setting.

EXPLORATORY OBJECTIVES:

I. To describe the toxicity profiles associated with chemo-immunotherapy in the Post-Consolidation setting according to the type of prior therapy.

II. To describe response to chemo-immunotherapy in the Post-Consolidation setting using the revised International Neuroblastoma Risk Classification (INRC) in patients with evaluable or measurable disease at study entry.

III. To characterize immune and cytokine profiles in patients receiving Post-Consolidation chemo-immunotherapy.

IV. To bank serial blood samples to investigate the relationship between factors related to the tumor, host, and immune environment and clinical outcomes in patients treated with chemo-immunotherapy.

OUTLINE:

Patients receive temozolomide orally (PO) or via enteral tube daily and irinotecan intravenously (IV) over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim subcutaneously (SC) or IV over 2 hours daily on days 6-12, and isotretinoin PO twice daily (BID) on days 8-21. Patients undergo multigated acquisition scan (MUGA) during screening. Patients also undergo magnetic resonance imaging (MRI), or computed tomography (CT), iobenguane I-123 (123I-MIBG), or fludeoxyglucose F-18-positron emission tomography (FDG-PET), bone marrow (BM) aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, and 60 months.

Eligibility Criteria:
Inclusion Criteria:

* Patients must be \< 31 years of age at the time of enrollment.
* Patients must have a diagnosis of 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 based on Children's Oncology Group (COG) risk classification. The following disease groups are eligible:

  * Patients with International Neuroblastoma Risk Group (INRG) Stage M disease with any of the following features:

    * MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
    * Age \> 547 days at the time of diagnosis regardless of biologic features; OR
    * Age 365-547 days at the time of diagnosis with tumors with unfavorable histology and/or deoxyribonucleic acid (DNA) index = 1
  * Patients with INRG Stage MS disease with MYCN amplification
  * Patients with INRG Stage L2 disease with either of the following features:

    * MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
    * Age \> 547 days at the time of diagnosis with MYCN non-amplified tumors with unfavorable histology
  * Note: Patients observed or patients treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet criteria will also be eligible
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years
* Prior therapy

  * All patients must have completed high-risk Induction therapy with 4-6 cycles of chemotherapy
  * After completion of Induction therapy, patients may have received no more than 4 cycles of bridging chemotherapy or chemo-immunotherapy prior to ASCT
  * Patients cannot have previously progressed on immunotherapy with dinutuximab or other anti-GD2 monoclonal antibody
  * All patients must have had undergone surgical resection of their primary tumor as part of frontline therapy. Exceptions to this requirement include patients who had a complete response to Induction chemotherapy, patients with no identifiable primary tumor, and patients for whom the institutional surgical team determined that potential risks outweighed potential benefits of resection
  * All patients must have undergone tandem high-dose chemotherapy with ASCT as part of Consolidation
  * Patients must enroll between day +56 and day +200 from the peripheral blood stem cell (PBSC) infusion following the last dose of high-dose chemotherapy during Consolidation
  * All patients must have undergone external beam radiation therapy. Exceptions to this requirement include patients who had no identifiable primary tumor and no persistent metastatic disease at the end of Induction. For patients who received radiotherapy, at least 7 days must have elapsed between completion of radiotherapy and enrollment on this study
* Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days of entry on this study. Seven days must have elapsed since administration of a short-acting myeloid growth factor
* Peripheral absolute neutrophil count (ANC) \>= 750/uL
* Platelet count \>= 50,000/uL (transfusion independent for \>= 7 days)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2, or a serum creatinine based on age/gender as follows:

  * Age: Maximum Serum Creatinine (mg/dL)
  * 6 months to \< 1 year: 0.5 (male and female)
  * 1 to \< 2 years: 0.6 (male and female)
  * 2 to \< 6 years: 0.8 (male and female)
  * 6 to \< 10 years: 1 (male and female)
  * 10 to \< 13 years: 1.2 (male and female)
  * 13 to \< 16 years: 1.5 (male), 1.4 (female)
  * \>= 16 years: 1.7 (male), 1.4 (female)

    * 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
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 5.0 x ULN for age (=\< 225 U/L)

  * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by echocardiogram or radionuclide angiogram
* Absence of dyspnea at rest
* If pulmonary function tests (PFTs) are performed, forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) must be \> 60%
* No clinical evidence of active central nervous system (CNS) disease at the time of study enrollment
* Patients with seizure disorder may be enrolled if on non-enzyme-inducing anticonvulsants and well controlled
* CNS toxicity from prior therapy =\< grade 2

Exclusion Criteria:

* Patients must not have had progressive disease (PD) per the revised International Neuroblastoma Risk Criteria (INRC) since the initial diagnosis of high-risk neuroblastoma

  * Exception: Progressive disease within the first 2 cycles of Induction chemotherapy consisting of cyclophosphamide and topotecan is allowed. Patients with progression subsequent to initial cyclophosphamide and topotecan cycles are excluded
* Patients may not have received additional systemic cancer-directed therapy following completion of the last planned high-dose chemotherapy with ASCT prior to enrollment on this trial
* Patients may not have received iodine-131 (131I)-metaiodobenzylguanidine (MIBG) therapy at any time prior to enrollment on this trial
* Patients who received single (rather than tandem) high-dose chemotherapy with ASCT are excluded
* Patients cannot be receiving other ongoing anticancer therapy
* Patients who were enrolled onto ANBL1531 AND underwent arm assignment are not eligible. Patients who enrolled onto ANBL1531 who declined second consent may be eligible for ANBL19P1 if all other criteria are met
* Patients enrolled onto ANBL17P1 are not eligible
* 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 2 mg/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

  * Note: 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. However, prior or planned concomitant treatment with eculizumab is permitted (e.g., treatment of TA-TMA)
* Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, valproic acid, or carbamazepine for at least 7 days prior to study enrollment

  * Note: Patients receiving non-enzyme inducing anticonvulsants such as gabapentin or levetiracetam are eligible
* Patients must not have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
* Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma
* Patients with symptoms of congestive heart failure are not eligible
* Patients with moderate or large pericardial effusions are not eligible
* Patients must not have \>= grade 2 diarrhea
* Patients must not have uncontrolled infection
* Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of the anti-GD2 therapy are not eligible
* Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met