Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma

1. Is the biology right?

• Somatic driver evidence: no · None of IL2RA, IL2RG, IL2RB, RARG, RARB, RARA, CSF2RA, CSF2RB has somatic-mutation evidence in neuroblastoma

  Rule: Open Targets has somatic-mutation evidence for the target in this cancer. Source: Open Targets: IL2RA in neuroblastoma, 2026-11-11
• Human genetic evidence: no · No germline or somatic evidence for IL2RA, IL2RG, IL2RB, RARG, RARB, RARA, CSF2RA, CSF2RB in neuroblastoma

  Rule: Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence. Source: Open Targets: IL2RA in neuroblastoma, 2026-11-11
• Pediatric target: no · Not on the FDA list

  Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study. Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
• Haematologic cancer: no · Solid tumour

  Rule: From the indication, or the registry conditions when no indication matches. Source: ClinicalTrials.gov NCT00026312, 2026-11-11

  Published context: Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid (BIO / Informa / QLS 2021, 2011–2020). Population-level, not a prediction.

• IL2RA (via Aldesleukin): Evidence types in neuroblastoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: IL2RA in neuroblastoma
• IL2RG (via Aldesleukin): Evidence types in neuroblastoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: IL2RG in neuroblastoma
• IL2RB (via Aldesleukin): Evidence types in neuroblastoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: IL2RB in neuroblastoma
• RARG (via Isotretinoin): Evidence types in neuroblastoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: RARG in neuroblastoma
• RARB (via Isotretinoin): Evidence types in neuroblastoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: RARB in neuroblastoma
• RARA (via Isotretinoin): Evidence types in neuroblastoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: RARA in neuroblastoma
• CSF2RA (via Sargramostim): Evidence types in neuroblastoma: clinical. Datasources: clinical_precedence. · Open Targets: CSF2RA in neuroblastoma
• CSF2RB (via Sargramostim): Evidence types in neuroblastoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: CSF2RB in neuroblastoma

• Not loaded on this app yet: Normal-tissue expression in vital organs. Source: Human Protein Atlas (ticket 36).
• Not loaded on this app yet: Pan-essential in cell lines. Source: DepMap (ticket 36).
• Not loaded on this app yet: Approved drug on this target. Source: Drugs@FDA (ticket 30).

2. Can the result be trusted?

• Randomised: yes · Randomised allocation

  Rule: Registry allocation field. Source: ClinicalTrials.gov NCT00026312, 2026-11-11
• Small denominator: no · 1449 enrolled; each patient moves a rate by 100 ÷ 1449 = 0.1 points

  Rule: Enrolment under 30; the arithmetic is shown, not a benchmark. Source: ClinicalTrials.gov NCT00026312, 2026-11-11
• Primary endpoint is overall survival: no · Event-Free Survival (EFS)

  Rule: A registered primary outcome measure names overall survival. Source: ClinicalTrials.gov NCT00026312, 2026-11-11

  Published context: Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3 (Otsuka 2021, 400 phase 3 oncology trials, to 2020). Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival.

  Published context: 52% of surrogate-to-OS correlations are low (Prasad 2015, published to 2014). Shown with the figure above.
• Results overdue: no · Results posted 2017-03-29

  Rule: Primary completion (actual) more than 12 months ago and no results posted to the registry. Source: ClinicalTrials.gov NCT00026312, 2026-11-11

• Not loaded on this app yet: Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff. Source: Readout extraction (ticket 32).
• Not loaded on this app yet: Primary endpoint changed between registry versions. Source: Registry versions in the store (ticket 32).

3. What must it beat?

• Not loaded on this app yet: Control-arm result and approved therapies for the same segment, with label links. Source: Drugs@FDA, FDA labels and readouts (tickets 30, 32).

4. Too crowded, or too late?

• Stopped on this target: 170 terminated, withdrawn or suspended trials of drugs against IL2RA; 28 give no reason. Reasons are quoted as the registry gives them on the target page. · IL2RA: what already stopped

• Not loaded on this app yet: Programs on the target by phase and months behind the leader. Source: Programs and Drugs@FDA (ticket 33).

5. Can it be approved, and stay approved?

• Single-country: no · 197 sites in 5 countries; 172 in the United States (87%)

  Rule: All listed sites are in one country; the share of US sites is shown. Source: ClinicalTrials.gov NCT00026312, 2026-11-11
• EU paediatric investigation plan: yes · EMA/PE/0000232765 (sargramostim, Treatment of pulmonary alveolar proteinosis): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 14 Apr 2025; EMA/PE/0000232765 (sargramostim, Treatment of pulmonary alveolar proteinosis): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 14 Apr 2025; EMEA-001556-PIP02-24 (aldesleukin, Treatment of amyotrophic lateral sclerosis): W: decision granting a waiver in all age groups for all conditions or indications, 13 Sept 2024; EMEA-003568-PIP01-23 (sargramostim, Treatment of acute radiation syndrome): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 27 Mar 2024; +1 more

  Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
• EU orphan designation: yes · EU/3/22/2701 withdrawn 11 Oct 2022: Treatment of autosomal recessive congenital ichthyosis; EU/3/23/2760 withdrawn 15 Feb 2023: Treatment of recessive X-linked ichthyosis; EU/3/24/2928 positive 28 Jun 2024: Treatment of pulmonary alveolar proteinosis; EU/3/22/2578 positive 24 Feb 2022: Treatment of amyotrophic lateral sclerosis; +2 more

  Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
• Authorised in the EU: yes · Imreplys: authorised since 21 Aug 2025, exceptional circumstances; Unituxin: withdrawn since 14 Aug 2015

  Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
• FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link

  Rule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
• FDA pediatric oncology approval: yes · Dinutuximab [Unituxin], 10 Mar 2015: In combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy

  Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
• Registered studies open to children: yes · 370 interventional studies of Aldesleukin, Dinutuximab, Isotretinoin, Sargramostim include patients under 18; 62 are recruiting, not yet recruiting or active

  Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11

• Caveat: Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality.
• Rare pediatric disease voucher: FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. · FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs

• Not loaded on this app yet: Precedent approvals for target, modality and endpoint; accelerated-approval status. Source: Drugs@FDA and FDA accelerated-approval tables (ticket 30).

6. Can the sponsor finish?

• Sponsor: National Cancer Institute (NCI) (academic or other) · ClinicalTrials.gov NCT00026312
• principal investigator: Alice L Yu, Children's Oncology Group · Person page

• Not loaded on this app yet: Filed cash, quarterly spend and the runway arithmetic. Source: SEC XBRL company facts (ticket 37).
• Not loaded on this app yet: Sponsor's completed vs stopped oncology trials and results-reporting record. Source: Registry, by company (ticket 37).

What public data cannot tell you

Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.