Please select the eligibility criteria that correspond to the clinical trial below.
Title: High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)
Brief Summary: This is a randomized study of the European SIOP Neuroblastoma Group (SIOPEN) in high-risk neuroblastoma (stages 2, 3, 4 and 4s MYCN-amplified neuroblastoma, stage 4 MYCN non amplified \> 12 months at diagnosis).

The protocol consists of a rapid, dose intensive induction chemotherapy, peripheral blood stem cell harvest, attempted complete excision of the primary tumour, myeloablative therapy followed by peripheral blood stem cell rescue, radiotherapy to the site of the primary tumour and immunotherapy (R4 randomization - isotretinoin and ch14.18/CHO (Dinutuximab beta, Qarziba ®).), with or without s.c. aldesleukin (IL-2)). Patients diagnosed after the closure of R3 randomization will not be R4 randomized. For these patients the use of ch14.18/CHO antibody is recommended without scIL-2 as continuous infusion as standard of care outside of controlled trials. ch14.18/CHO received marketing authorization by EMA in May 2017 (Qarziba ®).

In the induction phase, all patients receive Rapid COJEC following the result of the R3 randomization which was closed on June 8th, 2017 after inclusion of 630 patients as planned.

Following induction treatment peripheral blood stem cell harvest (PBSCH) is performed and complete excision of the primary tumour will be attempted.

Patients with an inadequate metastatic response to allow BuMel MAT followed by PBSCR at the end of induction should receive 2 TVD (Topotecan, Vincristine, Doxorubicin) cycles.

After Rapid COJEC induction, localized patients will proceed to consolidation. Patients aged 12-18 months at diagnosis, with stage 4 neuroblastoma, no MYCN amplification and without segmental chromosomal alterations (SCAs) are thought to have a good prognosis and will stop treatment after induction therapy and surgery to the primary tumour.

Consolidation consists of BuMel MAT based on the results of the R1 randomization followed by peripheral blood stem cell rescue (PBSCR) and radiotherapy to the site of the primary tumour.

The R2 immunotherapy randomization using ch14.18/CHO as 8 hour infusion on 5 consecutive days ( total dose (100mg/m²) with or without aldesleukin (IL-2) alternated with isotretinoin (13-cis-RA) is closed.

The amended R4 immunotherapy randomization using ch14.18/CHO as continuous infusion (total dose 100mg/m² over 10 days) with or without aldesleukin (IL-2) alternated with isotretinoin (13-cis-RA) has accrued according to plan with results pending awaiting data maturity and DMC approval.


Options:
A: Inclusion Criteria:

* Diagnosis:

  * Part A: Recurrent or refractory neuroblastoma or melanoma.
  * Part B: Recurrent or refractory neuroblastoma or melanoma.
  * Part C: Recurrent or refractory osteosarcoma and Ewing sarcoma.
* Age: ≤ 21 years of age at the time of enrollment (i.e. participants are eligible until they reach their 22nd birthday).
* Does not have a clinically significant neurologic deficit or objective peripheral neuropathy (greater than or equal to grade 2). Peripheral (sensory or motor) neuropathy related to limb sparing procedure or amputation is allowed.
* Life expectancy: at least 8 weeks.
* Organ Function: Must have adequate organ and marrow function
* Performance status: Karnofsky ≥ 50 for \> 10 years of age; Lansky ≥ 50 for children \< 10 years of age.
* Prior Therapy: Patient must have fully recovered from the acute toxic effects of all prior therapy prior to enrolling on study.

  * Myelosuppressive Chemotherapy: Must not have received myelosuppressive therapy within 2 weeks prior to study entry (4 weeks if nitrosurea).
  * Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with biologic agent, including retinoic acid. Participants receiving IVIG are eligible; however, participant must not receive IVIG during the 4 days of antibody infusion.
  * Radiation therapy: At least 2 weeks since prior local radiation therapy at the time of study entry.
  * Growth factors: Must not have received hematopoietic growth factors (G-CSF, GM-CSF) for at least 1 week prior to study entry.
  * Investigational agent: Must not have received investigational agent within 14 days of study entry.
  * Immune therapy: Must not have received immunosuppressive (including glucocorticoids), immunostimulatory or any immunomodulatory treatment within 2 weeks of study entry. Steroid containing inhalers, steroid replacement for adrenal insufficiency and steroid premedication for prevention of transfusion or imaging contrast agent-related allergic reaction will be permitted.
* Patients may have had prior CNS metastasis providing: CNS disease has been previously treated and CNS disease has been clinically stable for 4 weeks prior to study entry (assessment must be made by CT or MRI).
* Written informed consent following institutional and federal guidelines.

Exclusion Criteria:

* Prior monoclonal antibody: Participants having received in vivo monoclonal antibodies for biologic therapy or for tumor imaging are eligible provided they did not experience a severe allergic reaction with the antibody.
* Pregnancy or Breast Feeding: Study participants who are pregnant are not eligible for this study. Pregnancy tests must be obtained in girls who are \> 10 years of age or post-menarchal within 7 days prior to study enrollment. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during participation in the trial. Breast feeding should be discontinued if a mother wishes to participate in this study.
* Allergy: known hypersensitivity to other recombinant human antibodies.
* An uncontrolled infection.
B: Inclusion Criteria:

* • Established diagnosis of neuroblastoma according to the International Neuroblastoma Staging System (INSS).

  * Age below 21 years.
  * High risk neuroblastoma defined as either:

    1. INSS stage 2, 3, 4, and 4s with MYCN amplification, or
    2. INSS stage 4 without MYCN amplification aged \> 12 months at diagnosis
  * Patients who have received no previous chemotherapy except for one cycle of etoposide and carboplatin (VP16/Carbo). In this situation patients will receive Rapid COJEC induction and the first Rapid COJEC cycle may be replaced by the first cycle VP16/Carbo (etoposide / carboplatin).
  * Written informed consent, including agreement of parents or legal guardian for minors, to enter a randomised study if the criteria for randomisation are met.
  * Tumour cell material available for determination of biological prognostic factors.
  * Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
  * Registration of all eligibility criteria with the data centre within 6 weeks from diagnosis.
  * Provisional follow up of 5 years.
  * National and local ethical committee approval.

Exclusion Criteria:

Any negative answer concerning the inclusion criteria of the study

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C: Inclusion Criteria:

* 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
* For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound; patients must have ONE of the following:

  * First episode of recurrent disease following completion of aggressive multi-drug frontline therapy
  * First episode of progressive disease during aggressive multi-drug frontline therapy
  * Primary resistant/refractory disease (less than partial response by INRC) detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1, etc.)
* Patients must have at least ONE of the following:

  * Measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan obtained within 3 weeks prior to study entry; measurable is defined as \>= 10 mm in at least one dimension on spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates increased fludeoxyglucose (FDG) uptake on positron emission tomography (PET) scan
  * MIBG scan obtained within 3 weeks prior to study entry 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
  * Patients with resistant/refractory soft tissue disease that is not MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo biopsy to document the presence of viable neuroblastoma; biopsy is not required for patients who have new site of soft tissue disease (radiographic evidence of disease progression) regardless of whether progression occurs while receiving therapy or after completion of therapy
  * Note: Patients with elevated catecholamines (i.e., \> 2 x ULN) only or bone marrow disease only are NOT eligible for this study
* 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 of age
* Patients must have received frontline therapy (including surgery, chemotherapy, autologous stem cell transplant \[SCT\] +/- MIBG, immunotherapy, radiotherapy, and retinoids) but may NOT have received second line chemotherapy for resistant/refractory, relapsed disease or progressive disease
* At least 14 days must have elapsed since completion of myelosuppressive therapy
* At least 7 days must have elapsed since the completion of therapy with a non-myelosuppressive biologic agent or retinoid
* No interim time prior to study entry is required following prior radiation therapy (RT) for non-target lesions; however, patients must not have received radiation for a minimum of 4 weeks prior to study entry at the site of any lesion that will be identified as a target lesion to measure tumor response; lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma; palliative radiation is allowed to sites that will not be used to measure response during this study
* Patients are eligible \>= 6 weeks after autologous stem cell transplants or stem cell infusions as long as hematologic and other eligibility criteria have been met
* Patients are eligible \>= 6 weeks after therapeutic 131I-MIBG provided that all other eligibility criteria are met
* Subjects who have previously received anti-GD2 monoclonal antibodies for biologic therapy or for tumor imaging are eligible unless they have had progressive disease while receiving prior anti-GD2 therapy; subjects who have received autologous marrow infusions or autologous stem cell infusions that were purged using monoclonal antibody linked to beads, but no other form of anti-GD2 monoclonal antibody, are eligible
* 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 \>= 75,000/uL (transfusion independent)
* Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and platelet count criteria are met but are not evaluable for hematological toxicity
* Creatinine clearance or estimated radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or
* A serum creatinine =\< upper limit of normal (ULN) based on age/gender as follows:

  * Age 1 month to \< 6 months: 0.4 for males, 0.4 for females
  * Age 6 months to \< 1 year: 0.5 for males, 0.5 for females
  * Age 1 to \< 2 years: 0.6 for males, 0.6 for females
  * Age 2 to \< 6 years: 0.8 for males, 0.8 for females
  * Age 6 to \< 10 years: 1 for males, 1 for females
  * Age 10 to \< 13 years: 1.2 for males, 1.2 for females
  * Age 13 to \< 16 years: 1.5 for males, 1.4 for females
  * Age \>= 16 years: 1.7 for males, 1.4 for females
* Total bilirubin =\< 1.5 x ULN for age AND
* Serum glutamate pyruvate 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 45 U/L
* Adequate central nervous system function defined as:

  * Patients with a history of central nervous system (CNS) disease must have no clinical or radiological evidence of CNS disease at the time of study enrollment
  * Patients with seizure disorders may be enrolled if seizures are well controlled on anticonvulsants
  * CNS toxicity =\< grade 2
* Shortening fraction of \>= 27% by echocardiogram (ECHO) OR
* Ejection fraction \>= 50% by ECHO or gated radionuclide study
* Adequate coagulation defined as:

  * Prothrombin time (PT) =\< 1.2 x upper limit of normal
* Adequate pulmonary function defined as:

  * 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; normal pulmonary function tests in patients who are capable of cooperating with testing (including diffusion capacity of the lung of carbon monoxide \[DLCO\]) are required if there is a clinical indication for determination; 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; 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
* Patients with elevated catecholamines (i.e., \> 2 x ULN) only or bone marrow disease only are NOT eligible for this study
* 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; 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 must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, valproic acid, or carbamazepine for at least 7 days prior to study enrollment; patients receiving non-enzyme inducing anticonvulsants such as gabapentin or levetiracetam will be eligible
* 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 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
D: Inclusion Criteria:

* All patients must be diagnosed with neuroblastoma, and categorized as high risk at the time of diagnosis; exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible
* All patients must have completed therapy including intensive induction followed by ASCT and radiotherapy to be eligible for ANBL0032; radiotherapy may be waived for patients who either have small adrenal masses which are completely resected up front, or who never have an identifiable primary tumor; examples of such therapies include:

  * Following treatment per A3973 protocol
  * Following treatment per Pediatric Oncology Group (POG)-9341/9342 protocol
  * Following treatment per CCG3891
  * Following treatment on New Approaches to Neuroblastoma Therapy (NANT) 2001-02
  * Enrollment on or following treatment per ANBL02P1
  * Enrollment on or following treatment per ANBL07P1
  * Tandem transplant patients are eligible:

    * Following treatment on or per ANBL0532
    * Following treatment per POG 9640
    * Following treatment per COG ANBL00P1
    * Following treatment per CHP 594/Dana-Farber Cancer Institute (DFCI) 34-DAT
* No more than 12 months from the date of starting the first induction chemotherapy after diagnosis to the date of ASCT except for the rare occasions as noted below; for tandem ASCT patients, this will be the date of the FIRST stem cell infusion; exception: for those who are initially diagnosed as non-high risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma, the 12 months restriction should start from the date of induction therapy for high risk neuroblastoma (not from the initial induction therapy for non-high risk disease), to the date of ASCT
* At pre-ASCT evaluation patients must meet the International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases and bone metastases; patients who meet those criteria must also meet the protocol specified criteria for bone marrow response as outlined below:

  * =\< 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy
  * Patient who have no tumor seen on the prior bone marrow, and then have =\< 10% tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment evaluation will also be eligible (note that per INRC this would have been defined as "overall" response of progressive disease \[PD\])
* Prior to enrollment on ANBL0032, a determination of mandatory disease staging must be performed (tumor imaging studies including computed tomography \[CT\] or magnetic resonance imaging \[MRI\], MIBG scan, and vanillylmandelic acid \[VMA\]/homovanillic acid \[HVA\]; bone marrow aspirates are required but biopsy may be omitted if negative prior to ASCT); this disease assessment is required for eligibility and should be done preferably within 2 weeks, but must be done within a maximum of 4 weeks before enrollment

  * For those with residual disease before radiotherapy, re-evaluation of irradiated residual tumors is preferably performed at the earliest 5 days after completing radiotherapy; patients with residual disease are eligible; biopsy is not required; patients who have biopsy proven residual disease after ASCT will be enrolled on Stratum 07
  * Patients must not have progressive disease at the time of study enrollment except for protocol specified bone marrow response and except for elevations of catecholamines as the only sign of disease in a patient who had normal catecholamines at pre-ASCT evaluation
* Patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than ten (10) calendar days after the date of study enrollment; patients should be enrolled preferably between day 56 and day 85 after peripheral blood stem cell (PBSC) infusion (day from 2nd stem cell infusion for tandem transplant); patients must be enrolled no later than day 200 after PBSC infusion; enrollment must occur after completion of radiotherapy, and after completion of tumor assessment post-ASCT and radiotherapy; informed consent should be obtained within 3 weeks pre-ASCT up to the time of registration
* Patients must not have received prior anti-disialoganglioside (GD2) antibody therapy
* Patients must have a Lansky or Karnofsky performance scale score of \>= 50% and patients must have a life expectancy of \>= 2 months
* Total absolute phagocyte count (APC = %neutrophils + %monocytes) X white blood cell (WBC) is at least 1000/uL
* 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:

  * No greater than 0.4 mg/dL (1 month to \< 6 months)
  * No greater than 0.5 mg/dL (6 months to \< 1 year)
  * No greater than 0.6 mg/dL (1 to \< 2 years)
  * No greater than 0.8 mg/dL (2 to \< 6 years)
  * No greater than 1.0 mg/dL (6 to \< 10 years)
  * No greater than 1.2 mg/dL (10 to \< 13 years)
  * No greater than 1.4 mg/dL (\>= 13 years \[female\])
  * No greater than 1.5 mg/dL (13 to \< 16 years \[male\])
  * No greater than 1.7 mg/dL (\>= 16 years \[male\])
* Total bilirubin =\< 1.5 x normal
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 5 x normal
* Veno-occlusive disease, if present, should be stable or improving
* Shortening fraction of \>= 27% by echocardiogram, or if shortening fraction abnormal, ejection fraction of \>= 55% by gated radionuclide study or echocardiogram; note: the echocardiogram or gated radionuclide study must be performed within 4 weeks prior to enrollment
* Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) \> 60% predicted by pulmonary function test; for children who are unable to do pulmonary function tests (PFTs), no evidence of dyspnea at rest and no exercise intolerance should be documented; note: the pulmonary function test must be performed within 4 weeks prior to enrollment
* Patients with seizure disorder may be enrolled if on anticonvulsants and well-controlled; central nervous system (CNS) toxicity \< grade 2
* Written informed consent in accordance with institutional and Food and Drug Administration (FDA) guidelines must be obtained from parent or legal guardian
* Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method; female patients who are lactating must agree to stop breast-feeding

Answer: B