<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03786783</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2018-03732</org_study_id>
    <secondary_id>NCI-2018-03732</secondary_id>
    <secondary_id>ANBL17P1</secondary_id>
    <secondary_id>ANBL17P1</secondary_id>
    <secondary_id>U10CA180886</secondary_id>
    <nct_id>NCT03786783</nct_id>
  </id_info>
  <brief_title>Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma</brief_title>
  <official_title>A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim&#xD;
      work when combined with chemotherapy in patients with high-risk neuroblastoma. Immunotherapy&#xD;
      with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune&#xD;
      system and may interfere with the ability of tumor cells to grow and spread. Sargramostim&#xD;
      helps the body produce normal infection-fighting white blood cells. These cells also help the&#xD;
      dinutuximab work better. Giving chemotherapy before a stem cell transplant, with drugs such&#xD;
      as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan,&#xD;
      etoposide, carboplatin, topotecan, and isotretinoin, helps kill cancer cells that are in the&#xD;
      body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells).&#xD;
      Giving dinutuximab and sargramostim with combination chemotherapy may work better than&#xD;
      combination chemotherapy alone in treating patients with high-risk neuroblastoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To assess the feasibility and tolerability of administering ch14.18 (dinutuximab) and&#xD;
      sargramostim (GM-CSF) in combination with a multi-agent chemotherapy regimen during cycles&#xD;
      3-5 of the Induction phase for patients with newly-diagnosed high-risk neuroblastoma.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To describe the response rates, event-free survival (EFS) and overall survival (OS) for&#xD;
      patients receiving the combination of standard Induction chemotherapy and ch14.18&#xD;
      (dinutuximab) followed by tandem transplant, radiation therapy, and post-consolidation&#xD;
      immunotherapy.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To describe the clinical relevance of naturally occurring anti-glycan antibodies in&#xD;
      patients receiving ch14.18 (dinutuximab).&#xD;
&#xD;
      II. To describe the clinical relevance of natural killer (NK) receptor NKp30 isoforms in&#xD;
      patients receiving ch14.18 (dinutuximab).&#xD;
&#xD;
      III. To describe the association between host factors, including human anti-chimeric&#xD;
      antibodies (HACA), and response to protocol therapy.&#xD;
&#xD;
      IV. To describe the immune environment (gene expression; immune effector cells, activities&#xD;
      and signaling molecules; immune target expression) during and following treatment.&#xD;
&#xD;
      V. To describe the association between levels of circulating GD2, and tumor cell GD2&#xD;
      expression with response to therapy.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      INDUCTION CYCLES 1-2 (21 days): Patients receive cyclophosphamide intravenously (IV) over&#xD;
      15-30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days&#xD;
      for 2 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      INDUCTION CYCLE 3: Patients receive cisplatin IV over 1 hour on days 1-3, etoposide IV over 2&#xD;
      hours on days 1-3, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim&#xD;
      subcutaneously (SC) on day 6 or 7 of a 21-day cycle.&#xD;
&#xD;
      INDUCTION CYCLE 4: Patients receive vincristine IV over 1 minute on day 1, doxorubicin IV&#xD;
      over 1-15 minutes on days 1-2, cyclophosphamide IV over 1 hour on days 1-2, dinutuximab IV&#xD;
      over 10-20 hours on days 2-5, and sargramostim SC on day 6 or 7 of a 21-day cycle.&#xD;
&#xD;
      INDUCTION CYCLE 5: Patients receive cisplatin IV over 1 hour on days 1-3, etoposide IV over 2&#xD;
      hours on days 1-3, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC on day 6&#xD;
      or 7 of a 21-day cycle.&#xD;
&#xD;
      Patients may undergo surgery after the fourth or fifth cycle of Induction at the discretion&#xD;
      of treating doctor. Patients with stable disease or better tumor response at the end of&#xD;
      Induction proceed to Consolidation. Consolidation treatment begins between 4 and 6 weeks from&#xD;
      the start date of Induction chemotherapy cycle 5. For patients who have surgical resection&#xD;
      delayed until after Induction chemotherapy cycle 5, Consolidation starts within 4 weeks from&#xD;
      the date of surgery.&#xD;
&#xD;
      CONSOLIDATION #1: Patients receive thiotepa IV over 2 hours on days -7 to -5 and&#xD;
      cyclophosphamide IV over 1 hour on days -5 to -2. Patients then undergo autologous stem cell&#xD;
      transplant (ASCT) on day 0.&#xD;
&#xD;
      CONSOLIDATION #2: Patients receive melphalan IV over 30 minutes on days -7 to -5, etoposide&#xD;
      IV over 24 hours on days -7 to -4, and carboplatin IV over 24 hours on days -7 to -4.&#xD;
      Patients then undergo ASCT on day 0.&#xD;
&#xD;
      RADIATION THERAPY: Beginning 42-80 days following Consolidation #2, patients receive external&#xD;
      beam radiation therapy (EBRT) daily for up to 20 days.&#xD;
&#xD;
      Patients then receive post-Consolidation therapy starting at least 1 week following radiation&#xD;
      therapy.&#xD;
&#xD;
      POST-CONSOLIDATION CYCLES 1-5: Patients receive sargramostim SC on days 1-14, dinutuximab IV&#xD;
      over 10-20 hours on days 4-7, and isotretinoin orally (PO) twice daily (BID) on days 11-24.&#xD;
      Treatment repeats every 28 days in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      POST-CONSOLIDATION CYCLE 6: Patients receive isotretinoin PO BID on days 15-28 of a 28-day&#xD;
      cycle.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at months 3, 6, 9, 12, 15, 18,&#xD;
      24, 30, 36, 42, 48, 54, and 60.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 14, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Unacceptable Toxicity</measure>
    <time_frame>Up to the first 5 cycles of treatment</time_frame>
    <description>Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Who Are Feasibility &quot;Failure&quot;</measure>
    <time_frame>Up to the first 5 cycles of treatment</time_frame>
    <description>Feasibility &quot;failures&quot; were defined as patients that did not receive &gt;= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility &quot;failure&quot; rate together with a 95% confidence interval.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response Rate</measure>
    <time_frame>Up to the first 5 cycles of treatment</time_frame>
    <description>Per the revised INRC, response is comprised by responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites were assessed using Response Evaluation Criteria in Solid Tumors and MIBG scans or FDG-PET scans if the tumor was MIBG non-avid. Bone marrow was assessed by histology or immunohistochemistry and cytology or immunocytology. Complete response (CR) - All components meet criteria for CR. Partial response (PR) - PR in at least one component and all other components are either CR, minimal disease (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with progressive disease (PD). Minor response (MR) - PR or CR in at least one component but at least one other component with stable disease; no component with PD. Stable disease (SD) - Stable disease in one component with no better than SD or NI in any other component; no component with PD. Progressive disease (PD) - Any component with PD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free Survival</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Per the revised INRC, progressive disease is: 1) &gt; 20% increase in the longest diameter of the primary tumor, taking as reference the smallest sum and ¬&gt; increase of 5 mm in longest dimension, 2) Any new soft tissue lesion detected by CT/MRI that is MIBG avid or FDG-PET avid, 3) Any new soft tissue lesion seen on CT/MRI that is biopsied and found to be neuroblastoma or ganglioneuroblastoma, 4) Any new bone site that is MIBG avid, 5) Any new bone site that is FDG-PET avid and has CT/MRI findings of tumor or is histologically neuroblastoma or ganglioneuroblastoma 6) A metastatic soft tissue site with &gt; 20% increase in longest diameter, taking as reference the smallest sum on study, and with &gt; 5mm in sum of diameters of target soft tissue lesions, 7) A relative MIBG score ¬&gt; 1.2, 8) Bone marrow without tumor infiltration that becomes &gt;5% tumor infiltration, 9) Bone marrow with tumor infiltration that increases by &gt; 2-fold and has &gt; 20% tumor infiltration on reassessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Kaplan-Meier method was used to estimate overall survival (OS). OS was defined as the time from study enrollment to death. 1-year OS is provided.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of Naturally Occurring Anti-glycan Antibodies</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The Incidence of Naturally Occurring Anti-glycan Antibodies was calculated, including placement of a 95% CI on the incidence. In addition, anti-glycan levels prior to the start of Induction therapy and prior to the start of post-Consolidation therapy was compared with Wilcoxon's signed-rank test for paired data.</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of Natural Killer (NK) Receptor NKp30 Isoforms</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Assessed by calculating the incidence of NK receptor NKp30 isoforms, including placement of a 95% CI on the incidence.</description>
  </other_outcome>
  <other_outcome>
    <measure>Response of Host Factors, Including Naturally Occurring Anti-glycan Antibodies, KIR/KIR-L Genotyping, Fc Receptor Genotyping, Human Anti-chimeric Antibodies (HACA)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Explored with Fisher's exact test for categorical and Wilcoxon rank-sum test for continuous host factors. Both the presence/absence and level of naturally occurring anti-glycan antibodies was considered. For the KIR/KIR-L analysis, patients were categorized as either matched or mismatched. Patients were grouped into one of the three genotype subgroups of Fc receptor genotyping for that analysis. The presence/absence of HACA, anti-idiotype, and pretreatment anti-therapeutic antibodies (PATA)/anti-allotype antibody was considered for the HACA analysis.</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Environment (Gene Expression; Immune Effector Cells, Activities and Signaling Molecules; Immune Target Expression)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The incidence of NK receptor NKp30 isoforms was calculated, including placement of a 95% CI on each incidence rate. Summary statistics were generated for serum cytokine (IL6, CXCL9) levels and gene expression of circulating immune function cells.</description>
  </other_outcome>
  <other_outcome>
    <measure>Levels of Circulating GD2 and Tumor Cell GD2 Expression</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Assessed by exploring the relationship between response to treatment with &gt; PR (response vs. non- response) with circulating GD2 levels, and GD2 tumor cell expression following therapy with a Wilcoxon rank-sum test. Changes from baseline were also analyzed.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Ganglioneuroblastoma</condition>
  <condition>High Risk Neuroblastoma</condition>
  <arm_group>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>See Detailed Description</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Autologous Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Undergo ASCT</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>AHSCT</other_name>
    <other_name>Autologous</other_name>
    <other_name>Autologous Hematopoietic Cell Transplantation</other_name>
    <other_name>Autologous Stem Cell Transplant</other_name>
    <other_name>Autologous Stem Cell Transplantation</other_name>
    <other_name>Stem Cell Transplantation, Autologous</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Blastocarb</other_name>
    <other_name>Carboplat</other_name>
    <other_name>Carboplatin Hexal</other_name>
    <other_name>Carboplatino</other_name>
    <other_name>Carboplatinum</other_name>
    <other_name>Carbosin</other_name>
    <other_name>Carbosol</other_name>
    <other_name>Carbotec</other_name>
    <other_name>CBDCA</other_name>
    <other_name>Displata</other_name>
    <other_name>Ercar</other_name>
    <other_name>JM-8</other_name>
    <other_name>Nealorin</other_name>
    <other_name>Novoplatinum</other_name>
    <other_name>Paraplatin</other_name>
    <other_name>Paraplatin AQ</other_name>
    <other_name>Paraplatine</other_name>
    <other_name>Platinwas</other_name>
    <other_name>Ribocarbo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Abiplatin</other_name>
    <other_name>Blastolem</other_name>
    <other_name>Briplatin</other_name>
    <other_name>CDDP</other_name>
    <other_name>Cis-diammine-dichloroplatinum</other_name>
    <other_name>Cis-diamminedichloridoplatinum</other_name>
    <other_name>Cis-diamminedichloro Platinum (II)</other_name>
    <other_name>Cis-diamminedichloroplatinum</other_name>
    <other_name>Cis-dichloroammine Platinum (II)</other_name>
    <other_name>Cis-platinous Diamine Dichloride</other_name>
    <other_name>Cis-platinum</other_name>
    <other_name>Cis-platinum II</other_name>
    <other_name>Cis-platinum II Diamine Dichloride</other_name>
    <other_name>Cismaplat</other_name>
    <other_name>Cisplatina</other_name>
    <other_name>Cisplatinum</other_name>
    <other_name>Cisplatyl</other_name>
    <other_name>Citoplatino</other_name>
    <other_name>Citosin</other_name>
    <other_name>Cysplatyna</other_name>
    <other_name>DDP</other_name>
    <other_name>Lederplatin</other_name>
    <other_name>Metaplatin</other_name>
    <other_name>Neoplatin</other_name>
    <other_name>Peyrone's Chloride</other_name>
    <other_name>Peyrone's Salt</other_name>
    <other_name>Placis</other_name>
    <other_name>Plastistil</other_name>
    <other_name>Platamine</other_name>
    <other_name>Platiblastin</other_name>
    <other_name>Platiblastin-S</other_name>
    <other_name>Platinex</other_name>
    <other_name>Platinol</other_name>
    <other_name>Platinol- AQ</other_name>
    <other_name>Platinol-AQ</other_name>
    <other_name>Platinol-AQ VHA Plus</other_name>
    <other_name>Platinoxan</other_name>
    <other_name>Platinum</other_name>
    <other_name>Platinum Diamminodichloride</other_name>
    <other_name>Platiran</other_name>
    <other_name>Platistin</other_name>
    <other_name>Platosin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamide Monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexrazoxane</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>2, 6-Piperazinedione, 4,4'-propylenedi-, (P)- (8CI)</other_name>
    <other_name>2,6-Piperazinedione, 4, 4'-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI)</other_name>
    <other_name>ADR-529</other_name>
    <other_name>ICRF-187</other_name>
    <other_name>Razoxane (+)-form</other_name>
    <other_name>Soluble ICRF (L-isomer)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Dinutuximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Ch 14.18UTC</other_name>
    <other_name>Ch14.18</other_name>
    <other_name>MOAB Ch14.18</other_name>
    <other_name>monoclonal antibody Ch14.18</other_name>
    <other_name>Unituxin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Adriablastin</other_name>
    <other_name>Hydroxydaunomycin</other_name>
    <other_name>Hydroxyl Daunorubicin</other_name>
    <other_name>Hydroxyldaunorubicin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Demethyl Epipodophyllotoxin Ethylidine Glucoside</other_name>
    <other_name>EPEG</other_name>
    <other_name>Lastet</other_name>
    <other_name>Toposar</other_name>
    <other_name>Vepesid</other_name>
    <other_name>VP 16</other_name>
    <other_name>VP 16-213</other_name>
    <other_name>VP-16</other_name>
    <other_name>VP-16-213</other_name>
    <other_name>VP16</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>External Beam Radiation Therapy</intervention_name>
    <description>Undergo EBRT</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Definitive Radiation Therapy</other_name>
    <other_name>EBRT</other_name>
    <other_name>External Beam Radiation</other_name>
    <other_name>External Beam Radiotherapy</other_name>
    <other_name>External Beam RT</other_name>
    <other_name>external radiation</other_name>
    <other_name>External Radiation Therapy</other_name>
    <other_name>external-beam radiation</other_name>
    <other_name>Radiation, External Beam</other_name>
    <other_name>Teleradiotherapy</other_name>
    <other_name>Teletherapy</other_name>
    <other_name>Teletherapy Radiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isotretinoin</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>13-cis retinoic acid</other_name>
    <other_name>13-cis-Retinoate</other_name>
    <other_name>13-cis-Retinoic Acid</other_name>
    <other_name>13-cis-Vitamin A Acid</other_name>
    <other_name>13-cRA</other_name>
    <other_name>Absorica</other_name>
    <other_name>Accure</other_name>
    <other_name>Accutane</other_name>
    <other_name>Amnesteem</other_name>
    <other_name>cis-Retinoic Acid</other_name>
    <other_name>Cistane</other_name>
    <other_name>Claravis</other_name>
    <other_name>Isotretinoinum</other_name>
    <other_name>Isotrex</other_name>
    <other_name>Isotrexin</other_name>
    <other_name>Myorisan</other_name>
    <other_name>Neovitamin A</other_name>
    <other_name>Neovitamin A Acid</other_name>
    <other_name>Oratane</other_name>
    <other_name>Retinoicacid-13-cis</other_name>
    <other_name>Ro 4-3780</other_name>
    <other_name>Ro-4-3780</other_name>
    <other_name>Roaccutan</other_name>
    <other_name>Roaccutane</other_name>
    <other_name>Roacutan</other_name>
    <other_name>Sotret</other_name>
    <other_name>ZENATANE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Alanine Nitrogen Mustard</other_name>
    <other_name>CB-3025</other_name>
    <other_name>L-PAM</other_name>
    <other_name>L-Phenylalanine Mustard</other_name>
    <other_name>L-Sarcolysin</other_name>
    <other_name>L-Sarcolysin Phenylalanine mustard</other_name>
    <other_name>L-Sarcolysine</other_name>
    <other_name>Melphalanum</other_name>
    <other_name>Phenylalanine Mustard</other_name>
    <other_name>Phenylalanine Nitrogen Mustard</other_name>
    <other_name>Sarcoclorin</other_name>
    <other_name>Sarkolysin</other_name>
    <other_name>WR-19813</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Sargramostim</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>23-L-Leucinecolony-Stimulating Factor 2</other_name>
    <other_name>DRG-0012</other_name>
    <other_name>Leukine</other_name>
    <other_name>Prokine</other_name>
    <other_name>rhu GM-CFS</other_name>
    <other_name>Sagramostim</other_name>
    <other_name>Sargramostatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thiotepa</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>1,1',1''-Phosphinothioylidynetrisaziridine</other_name>
    <other_name>Girostan</other_name>
    <other_name>N,N', N''-Triethylenethiophosphoramide</other_name>
    <other_name>Oncotiotepa</other_name>
    <other_name>STEPA</other_name>
    <other_name>Tepadina</other_name>
    <other_name>TESPA</other_name>
    <other_name>Tespamin</other_name>
    <other_name>Tespamine</other_name>
    <other_name>Thio-Tepa</other_name>
    <other_name>Thiofosfamide</other_name>
    <other_name>Thiofozil</other_name>
    <other_name>Thiophosphamide</other_name>
    <other_name>Thiophosphoramide</other_name>
    <other_name>Thiotef</other_name>
    <other_name>Tifosyl</other_name>
    <other_name>TIO TEF</other_name>
    <other_name>Tio-tef</other_name>
    <other_name>Triethylene Thiophosphoramide</other_name>
    <other_name>Triethylenethiophosphoramide</other_name>
    <other_name>Tris(1-aziridinyl)phosphine sulfide</other_name>
    <other_name>TSPA</other_name>
    <other_name>WR 45312</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topotecan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Hycamptamine</other_name>
    <other_name>Topotecan Lactone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)</arm_group_label>
    <other_name>Leurocristine</other_name>
    <other_name>VCR</other_name>
    <other_name>Vincrystine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL17P1.&#xD;
&#xD;
          -  Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular)&#xD;
             verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone&#xD;
             marrow with elevated urinary catecholamine metabolites. The following disease groups&#xD;
             are eligible:&#xD;
&#xD;
               -  Patients with International Neuroblastoma Risk Group (INRG) stage M disease are&#xD;
                  eligible if found to have either of the following features:&#xD;
&#xD;
                    -  MYCN amplification (&gt; 4-fold increase in MYCN signals as compared to&#xD;
                       reference signals), regardless of age or additional biologic features; OR&#xD;
&#xD;
                    -  Age &gt; 547 days regardless of biologic features;&#xD;
&#xD;
               -  Patients with INRG stage MS disease with MYCN amplification&#xD;
&#xD;
               -  Patients with INRG stage L2 disease with MYCN amplification&#xD;
&#xD;
               -  Patients &gt; 547 days of age initially diagnosed with INRG stage L1, L2 or MS&#xD;
                  disease who progress to stage M without prior chemotherapy may enroll within 4&#xD;
                  weeks of progression to stage M.&#xD;
&#xD;
               -  Patients &gt;= 365 days of age initially diagnosed with MYCN amplified INRG stage L1&#xD;
                  disease who progress to stage M without systemic therapy may enroll within 4&#xD;
                  weeks of progression to stage M.&#xD;
&#xD;
          -  Patients initially recognized to have high-risk disease must have had no prior&#xD;
             systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis&#xD;
             and within allowed timing as described).&#xD;
&#xD;
          -  Patients observed or treated with a single cycle of chemotherapy per a low or&#xD;
             intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar)&#xD;
             for what initially appeared to be non-high risk disease but subsequently found to meet&#xD;
             the criteria will also be eligible.&#xD;
&#xD;
          -  Patients who receive localized emergency radiation to sites of life-threatening or&#xD;
             function-threatening disease prior to or immediately after establishment of the&#xD;
             definitive diagnosis will be eligible.&#xD;
&#xD;
          -  Creatinine clearance (CrCl) or radioisotope glomerular filtration rate (GFR) &gt;= 70&#xD;
             mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:&#xD;
&#xD;
               -  Age 1 month to &lt; 6 months (male 0.4 mg/dL, female 0.4 mg/dL)&#xD;
&#xD;
               -  Age 6 months to &lt; 1 year (male 0.5 mg/dL, female 0.5 mg/dL)&#xD;
&#xD;
               -  Age 1 to &lt; 2 years (male 0.6 mg/dL, female 0.6 mg/dL)&#xD;
&#xD;
               -  Age 2 to &lt; 6 years (male 0.8 mg/dL, female 0.8 mg/dL)&#xD;
&#xD;
               -  Age 6 to &lt; 10 years (male 1 mg/dL, female 1 mg/dL)&#xD;
&#xD;
               -  Age 10 to &lt; 13 years (male 1.2 mg/dL, female 1.2 mg/dL)&#xD;
&#xD;
               -  Age 13 to &lt; 16 years (male 1.5 mg/dL, female 1.4 mg/dL)&#xD;
&#xD;
               -  Age &gt;= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to&#xD;
                  enrollment).&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN) for age (within 7 days prior to&#xD;
             enrollment).&#xD;
&#xD;
          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) &lt; 10 x&#xD;
             ULN. For the purposes of this study, ULN for ALT is 45 IU/L (within 7 days prior to&#xD;
             enrollment).&#xD;
&#xD;
          -  Shortening fraction of &gt;= 27% by echocardiogram (within 7 days prior to enrollment).&#xD;
&#xD;
          -  Ejection fraction of &gt;= 50% by echocardiogram or radionuclide angiogram (within 7 days&#xD;
             prior to enrollment).&#xD;
&#xD;
          -  No known contraindication to peripheral blood stem cell (PBSC) collection. Examples of&#xD;
             contraindications might be a weight or size less than the collecting institution finds&#xD;
             feasible, or a physical condition that would limit the ability of the child to undergo&#xD;
             apheresis catheter placement (if necessary) and/or the apheresis procedure.&#xD;
&#xD;
          -  All patients and/or their parents or legal guardians must sign a written informed&#xD;
             consent.&#xD;
&#xD;
          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute&#xD;
             (NCI) requirements for human studies must be met.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients &gt;18 months of age with INRG stage L2, MYCN non-amplified, regardless of&#xD;
             additional biologic features.&#xD;
&#xD;
          -  Patients with bone marrow failure syndromes.&#xD;
&#xD;
          -  Patients that are &gt;= 12 and =&lt; 18 months of age with INRG stage M and all 3 favorable&#xD;
             biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic&#xD;
             acid [DNA] index &gt; 1) are not eligible.&#xD;
&#xD;
          -  Patients on immunosuppressive medications (e.g. tacrolimus, cyclosporine,&#xD;
             corticosteroids for reasons other than prevention/treatment of allergic reactions,&#xD;
             adrenal replacement therapy, etc.) are not eligible.&#xD;
&#xD;
          -  Female patients who are pregnant are ineligible since fetal toxicities and teratogenic&#xD;
             effects have been noted for several of the study drugs. A pregnancy test is required&#xD;
             for female patients of childbearing potential.&#xD;
&#xD;
          -  Lactating females who plan to breastfeed their infants.&#xD;
&#xD;
          -  Sexually active patients of reproductive potential who have not agreed to use an&#xD;
             effective contraceptive method during study therapy and for two months after the last&#xD;
             dose of ch14.18 (dinutuximab) are not eligible.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sara M Federico</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Oncology Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Primary Children's Hospital</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital at Westmead</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Children's Hospital</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Starship Children's Hospital</name>
      <address>
        <city>Grafton</city>
        <state>Auckland</state>
        <zip>1145</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>New Zealand</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 24, 2018</study_first_submitted>
  <study_first_submitted_qc>December 24, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <results_first_submitted>December 16, 2022</results_first_submitted>
  <results_first_submitted_qc>February 14, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 14, 2023</results_first_posted>
  <last_update_submitted>February 14, 2023</last_update_submitted>
  <last_update_submitted_qc>February 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuroblastoma</mesh_term>
    <mesh_term>Ganglioneuroblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin A</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Melphalan</mesh_term>
    <mesh_term>Mechlorethamine</mesh_term>
    <mesh_term>Thiotepa</mesh_term>
    <mesh_term>Nitrogen Mustard Compounds</mesh_term>
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Etoposide phosphate</mesh_term>
    <mesh_term>Daunorubicin</mesh_term>
    <mesh_term>Topotecan</mesh_term>
    <mesh_term>Tretinoin</mesh_term>
    <mesh_term>Podophyllotoxin</mesh_term>
    <mesh_term>Dinutuximab</mesh_term>
    <mesh_term>Dexrazoxane</mesh_term>
    <mesh_term>Razoxane</mesh_term>
    <mesh_term>3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione</mesh_term>
    <mesh_term>Isotretinoin</mesh_term>
    <mesh_term>Sargramostim</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page</ipd_description>
    <ipd_url>https://grants.nih.gov/policy/sharing.htm</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 24, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03786783/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients with newly diagnosed high-risk Neuroblastoma enrolled between 1/14/2019 and 9/4/2020 across 10 institutions.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)</title>
          <description>Patients receive 5 cycles of Induction chemotherapy including cyclophosphamide, topotecan, cisplatin, etoposide, dinutuximab, sargramostim, vincristine, and doxorubicin. Patients may undergo surgery after Cycle 4 or 5 of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at end of Induction proceed to Consolidation. Consolidation treatment begins between 4-6 weeks from the start date of Induction cycle 5. For patients who have surgical resection delayed until after Induction cycle 5, Consolidation starts within 4 weeks from the date of surgery. Patients then undergo 2 cycles of Consolidation including thiotepa, cyclophosphamide, melphalan, etoposide, and carboplatin, followed by Radiation therapy beginning 42-80 days following Consolidation Cycle #2. Patients then receive 6 cycles of post-Consolidation therapy starting at least 1 week following radiation therapy, including sargramostim, dinutuximab, and isotretinoin.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease Progression</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient/Parent Refusal</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)</title>
          <description>Patients receive 5 cycles of Induction chemotherapy including cyclophosphamide, topotecan, cisplatin, etoposide, dinutuximab, sargramostim, vincristine, and doxorubicin. Patients may undergo surgery after Cycle 4 or 5 of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at end of Induction proceed to Consolidation. Consolidation treatment begins between 4-6 weeks from the start date of Induction cycle 5. For patients who have surgical resection delayed until after Induction cycle 5, Consolidation starts within 4 weeks from the date of surgery. Patients then undergo 2 cycles of Consolidation including thiotepa, cyclophosphamide, melphalan, etoposide, and carboplatin, followed by Radiation therapy beginning 42-80 days following Consolidation Cycle #2. Patients then receive 6 cycles of post-Consolidation therapy starting at least 1 week following radiation therapy, including sargramostim, dinutuximab, and isotretinoin.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="42"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.4" lower_limit="0.3" upper_limit="17.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>New Zealand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Unacceptable Toxicity</title>
        <description>Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.</description>
        <time_frame>Up to the first 5 cycles of treatment</time_frame>
        <population>All eligible patients who received at least one dose of ch14.18 (dinutuximab) during Induction cycles</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)</title>
            <description>Patients receive 5 cycles of Induction chemotherapy including cyclophosphamide, topotecan, cisplatin, etoposide, dinutuximab, sargramostim, vincristine, and doxorubicin. Patients may undergo surgery after Cycle 4 or 5 of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at end of Induction proceed to Consolidation. Consolidation treatment begins between 4-6 weeks from the start date of Induction cycle 5. For patients who have surgical resection delayed until after Induction cycle 5, Consolidation starts within 4 weeks from the date of surgery. Patients then undergo 2 cycles of Consolidation including thiotepa, cyclophosphamide, melphalan, etoposide, and carboplatin, followed by Radiation therapy beginning 42-80 days following Consolidation Cycle #2. Patients then receive 6 cycles of post-Consolidation therapy starting at least 1 week following radiation therapy, including sargramostim, dinutuximab, and isotretinoin.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Unacceptable Toxicity</title>
          <description>Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.</description>
          <population>All eligible patients who received at least one dose of ch14.18 (dinutuximab) during Induction cycles</population>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.0" upper_limit="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Are Feasibility &quot;Failure&quot;</title>
        <description>Feasibility &quot;failures&quot; were defined as patients that did not receive &gt;= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility &quot;failure&quot; rate together with a 95% confidence interval.</description>
        <time_frame>Up to the first 5 cycles of treatment</time_frame>
        <population>All eligible patients who received at least one dose of ch14.18 (dinutuximab) during Induction cycles</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)</title>
            <description>Patients receive 5 cycles of Induction chemotherapy including cyclophosphamide, topotecan, cisplatin, etoposide, dinutuximab, sargramostim, vincristine, and doxorubicin. Patients may undergo surgery after Cycle 4 or 5 of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at end of Induction proceed to Consolidation. Consolidation treatment begins between 4-6 weeks from the start date of Induction cycle 5. For patients who have surgical resection delayed until after Induction cycle 5, Consolidation starts within 4 weeks from the date of surgery. Patients then undergo 2 cycles of Consolidation including thiotepa, cyclophosphamide, melphalan, etoposide, and carboplatin, followed by Radiation therapy beginning 42-80 days following Consolidation Cycle #2. Patients then receive 6 cycles of post-Consolidation therapy starting at least 1 week following radiation therapy, including sargramostim, dinutuximab, and isotretinoin.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Are Feasibility &quot;Failure&quot;</title>
          <description>Feasibility &quot;failures&quot; were defined as patients that did not receive &gt;= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility &quot;failure&quot; rate together with a 95% confidence interval.</description>
          <population>All eligible patients who received at least one dose of ch14.18 (dinutuximab) during Induction cycles</population>
          <units>Percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.0" upper_limit="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response Rate</title>
        <description>Per the revised INRC, response is comprised by responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites were assessed using Response Evaluation Criteria in Solid Tumors and MIBG scans or FDG-PET scans if the tumor was MIBG non-avid. Bone marrow was assessed by histology or immunohistochemistry and cytology or immunocytology. Complete response (CR) - All components meet criteria for CR. Partial response (PR) - PR in at least one component and all other components are either CR, minimal disease (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with progressive disease (PD). Minor response (MR) - PR or CR in at least one component but at least one other component with stable disease; no component with PD. Stable disease (SD) - Stable disease in one component with no better than SD or NI in any other component; no component with PD. Progressive disease (PD) - Any component with PD.</description>
        <time_frame>Up to the first 5 cycles of treatment</time_frame>
        <population>All eligible patients. Institutional assessment of end-induction response has been used.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)</title>
            <description>Patients receive 5 cycles of Induction chemotherapy including cyclophosphamide, topotecan, cisplatin, etoposide, dinutuximab, sargramostim, vincristine, and doxorubicin. Patients may undergo surgery after Cycle 4 or 5 of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at end of Induction proceed to Consolidation. Consolidation treatment begins between 4-6 weeks from the start date of Induction cycle 5. For patients who have surgical resection delayed until after Induction cycle 5, Consolidation starts within 4 weeks from the date of surgery. Patients then undergo 2 cycles of Consolidation including thiotepa, cyclophosphamide, melphalan, etoposide, and carboplatin, followed by Radiation therapy beginning 42-80 days following Consolidation Cycle #2. Patients then receive 6 cycles of post-Consolidation therapy starting at least 1 week following radiation therapy, including sargramostim, dinutuximab, and isotretinoin.</description>
          </group>
        </group_list>
        <measure>
          <title>Response Rate</title>
          <description>Per the revised INRC, response is comprised by responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites were assessed using Response Evaluation Criteria in Solid Tumors and MIBG scans or FDG-PET scans if the tumor was MIBG non-avid. Bone marrow was assessed by histology or immunohistochemistry and cytology or immunocytology. Complete response (CR) - All components meet criteria for CR. Partial response (PR) - PR in at least one component and all other components are either CR, minimal disease (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with progressive disease (PD). Minor response (MR) - PR or CR in at least one component but at least one other component with stable disease; no component with PD. Stable disease (SD) - Stable disease in one component with no better than SD or NI in any other component; no component with PD. Progressive disease (PD) - Any component with PD.</description>
          <population>All eligible patients. Institutional assessment of end-induction response has been used.</population>
          <units>Percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.6" lower_limit="64.1" upper_limit="88.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Event-free Survival</title>
        <description>Per the revised INRC, progressive disease is: 1) &gt; 20% increase in the longest diameter of the primary tumor, taking as reference the smallest sum and ¬&gt; increase of 5 mm in longest dimension, 2) Any new soft tissue lesion detected by CT/MRI that is MIBG avid or FDG-PET avid, 3) Any new soft tissue lesion seen on CT/MRI that is biopsied and found to be neuroblastoma or ganglioneuroblastoma, 4) Any new bone site that is MIBG avid, 5) Any new bone site that is FDG-PET avid and has CT/MRI findings of tumor or is histologically neuroblastoma or ganglioneuroblastoma 6) A metastatic soft tissue site with &gt; 20% increase in longest diameter, taking as reference the smallest sum on study, and with &gt; 5mm in sum of diameters of target soft tissue lesions, 7) A relative MIBG score ¬&gt; 1.2, 8) Bone marrow without tumor infiltration that becomes &gt;5% tumor infiltration, 9) Bone marrow with tumor infiltration that increases by &gt; 2-fold and has &gt; 20% tumor infiltration on reassessment.</description>
        <time_frame>Up to 1 year</time_frame>
        <population>All eligible patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)</title>
            <description>Patients receive 5 cycles of Induction chemotherapy including cyclophosphamide, topotecan, cisplatin, etoposide, dinutuximab, sargramostim, vincristine, and doxorubicin. Patients may undergo surgery after Cycle 4 or 5 of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at end of Induction proceed to Consolidation. Consolidation treatment begins between 4-6 weeks from the start date of Induction cycle 5. For patients who have surgical resection delayed until after Induction cycle 5, Consolidation starts within 4 weeks from the date of surgery. Patients then undergo 2 cycles of Consolidation including thiotepa, cyclophosphamide, melphalan, etoposide, and carboplatin, followed by Radiation therapy beginning 42-80 days following Consolidation Cycle #2. Patients then receive 6 cycles of post-Consolidation therapy starting at least 1 week following radiation therapy, including sargramostim, dinutuximab, and isotretinoin.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-free Survival</title>
          <description>Per the revised INRC, progressive disease is: 1) &gt; 20% increase in the longest diameter of the primary tumor, taking as reference the smallest sum and ¬&gt; increase of 5 mm in longest dimension, 2) Any new soft tissue lesion detected by CT/MRI that is MIBG avid or FDG-PET avid, 3) Any new soft tissue lesion seen on CT/MRI that is biopsied and found to be neuroblastoma or ganglioneuroblastoma, 4) Any new bone site that is MIBG avid, 5) Any new bone site that is FDG-PET avid and has CT/MRI findings of tumor or is histologically neuroblastoma or ganglioneuroblastoma 6) A metastatic soft tissue site with &gt; 20% increase in longest diameter, taking as reference the smallest sum on study, and with &gt; 5mm in sum of diameters of target soft tissue lesions, 7) A relative MIBG score ¬&gt; 1.2, 8) Bone marrow without tumor infiltration that becomes &gt;5% tumor infiltration, 9) Bone marrow with tumor infiltration that increases by &gt; 2-fold and has &gt; 20% tumor infiltration on reassessment.</description>
          <population>All eligible patients.</population>
          <units>Percent Probability</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.6" lower_limit="70.8" upper_limit="94.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Kaplan-Meier method was used to estimate overall survival (OS). OS was defined as the time from study enrollment to death. 1-year OS is provided.</description>
        <time_frame>Up to 1 year</time_frame>
        <population>All eligible patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)</title>
            <description>Patients receive 5 cycles of Induction chemotherapy including cyclophosphamide, topotecan, cisplatin, etoposide, dinutuximab, sargramostim, vincristine, and doxorubicin. Patients may undergo surgery after Cycle 4 or 5 of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at end of Induction proceed to Consolidation. Consolidation treatment begins between 4-6 weeks from the start date of Induction cycle 5. For patients who have surgical resection delayed until after Induction cycle 5, Consolidation starts within 4 weeks from the date of surgery. Patients then undergo 2 cycles of Consolidation including thiotepa, cyclophosphamide, melphalan, etoposide, and carboplatin, followed by Radiation therapy beginning 42-80 days following Consolidation Cycle #2. Patients then receive 6 cycles of post-Consolidation therapy starting at least 1 week following radiation therapy, including sargramostim, dinutuximab, and isotretinoin.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Kaplan-Meier method was used to estimate overall survival (OS). OS was defined as the time from study enrollment to death. 1-year OS is provided.</description>
          <population>All eligible patients.</population>
          <units>Percent Probability</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.0" lower_limit="88.1" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Incidence of Naturally Occurring Anti-glycan Antibodies</title>
        <description>The Incidence of Naturally Occurring Anti-glycan Antibodies was calculated, including placement of a 95% CI on the incidence. In addition, anti-glycan levels prior to the start of Induction therapy and prior to the start of post-Consolidation therapy was compared with Wilcoxon's signed-rank test for paired data.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Incidence of Natural Killer (NK) Receptor NKp30 Isoforms</title>
        <description>Assessed by calculating the incidence of NK receptor NKp30 isoforms, including placement of a 95% CI on the incidence.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Response of Host Factors, Including Naturally Occurring Anti-glycan Antibodies, KIR/KIR-L Genotyping, Fc Receptor Genotyping, Human Anti-chimeric Antibodies (HACA)</title>
        <description>Explored with Fisher's exact test for categorical and Wilcoxon rank-sum test for continuous host factors. Both the presence/absence and level of naturally occurring anti-glycan antibodies was considered. For the KIR/KIR-L analysis, patients were categorized as either matched or mismatched. Patients were grouped into one of the three genotype subgroups of Fc receptor genotyping for that analysis. The presence/absence of HACA, anti-idiotype, and pretreatment anti-therapeutic antibodies (PATA)/anti-allotype antibody was considered for the HACA analysis.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Immune Environment (Gene Expression; Immune Effector Cells, Activities and Signaling Molecules; Immune Target Expression)</title>
        <description>The incidence of NK receptor NKp30 isoforms was calculated, including placement of a 95% CI on each incidence rate. Summary statistics were generated for serum cytokine (IL6, CXCL9) levels and gene expression of circulating immune function cells.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Levels of Circulating GD2 and Tumor Cell GD2 Expression</title>
        <description>Assessed by exploring the relationship between response to treatment with &gt; PR (response vs. non- response) with circulating GD2 levels, and GD2 tumor cell expression following therapy with a Wilcoxon rank-sum test. Changes from baseline were also analyzed.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>While patients were on Protocol Therapy, an average of 12 months</time_frame>
      <desc>Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the &quot;AE Other&quot; table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)</title>
          <description>Patients receive 5 cycles of Induction chemotherapy including cyclophosphamide, topotecan, cisplatin, etoposide, dinutuximab, sargramostim, vincristine, and doxorubicin. Patients may undergo surgery after Cycle 4 or 5 of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at end of Induction proceed to Consolidation. Consolidation treatment begins between 4-6 weeks from the start date of Induction cycle 5. For patients who have surgical resection delayed until after Induction cycle 5, Consolidation starts within 4 weeks from the date of surgery. Patients then undergo 2 cycles of Consolidation including thiotepa, cyclophosphamide, melphalan, etoposide, and carboplatin, followed by Radiation therapy beginning 42-80 days following Consolidation Cycle #2. Patients then receive 6 cycles of post-Consolidation therapy starting at least 1 week following radiation therapy, including sargramostim, dinutuximab, and isotretinoin.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hemolytic uremic syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Chylous ascites</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Duodenal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Small intestinal mucositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>GGT increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Adult respiratory distress syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Chylothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Left ventricular systolic dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Congenital, familial and genetic disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Anal mucositis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Intra-abdominal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Jejunal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Malabsorption</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Rectal mucositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Small intestinal mucositis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Typhlitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Sinusoidal obstruction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Anorectal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Catheter related infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Fungemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Shingles</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Splenic infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Thrush</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Viremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Vulval infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Vascular access complication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>GGT increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Thyroid stimulating hormone increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Bronchospasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pharyngeal mucositis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pulmonary edema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Results Reporting Coordinator</name_or_title>
      <organization>Children's Oncology Group</organization>
      <phone>16264470064</phone>
      <email>resultsreportingcoordinator@childrensoncologygroup.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03786783
org study id: NCI-2018-03732
secondary id: NCI-2018-03732
secondary id: ANBL17P1
secondary id: ANBL17P1
secondary id: U10CA180886
nct id: NCT03786783
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim
      work when combined with chemotherapy in patients with high-risk neuroblastoma. Immunotherapy
      with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune
      system and may interfere with the ability of tumor cells to grow and spread. Sargramostim
      helps the body produce normal infection-fighting white blood cells. These cells also help the
      dinutuximab work better. Giving chemotherapy before a stem cell transplant, with drugs such
      as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan,
      etoposide, carboplatin, topotecan, and isotretinoin, helps kill cancer cells that are in the
      body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells).
      Giving dinutuximab and sargramostim with combination chemotherapy may work better than
      combination chemotherapy alone in treating patients with high-risk neuroblastoma.
PRIMARY OBJECTIVE:

      I. To assess the feasibility and tolerability of administering ch14.18 (dinutuximab) and
      sargramostim (GM-CSF) in combination with a multi-agent chemotherapy regimen during cycles
      3-5 of the Induction phase for patients with newly-diagnosed high-risk neuroblastoma.

      SECONDARY OBJECTIVE:

      I. To describe the response rates, event-free survival (EFS) and overall survival (OS) for
      patients receiving the combination of standard Induction chemotherapy and ch14.18
      (dinutuximab) followed by tandem transplant, radiation therapy, and post-consolidation
      immunotherapy.

      EXPLORATORY OBJECTIVES:

      I. To describe the clinical relevance of naturally occurring anti-glycan antibodies in
      patients receiving ch14.18 (dinutuximab).

      II. To describe the clinical relevance of natural killer (NK) receptor NKp30 isoforms in
      patients receiving ch14.18 (dinutuximab).

      III. To describe the association between host factors, including human anti-chimeric
      antibodies (HACA), and response to protocol therapy.

      IV. To describe the immune environment (gene expression; immune effector cells, activities
      and signaling molecules; immune target expression) during and following treatment.

      V. To describe the association between levels of circulating GD2, and tumor cell GD2
      expression with response to therapy.

      OUTLINE:

      INDUCTION CYCLES 1-2 (21 days): Patients receive cyclophosphamide intravenously (IV) over
      15-30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days
      for 2 cycles in the absence of disease progression or unacceptable toxicity.

      INDUCTION CYCLE 3: Patients receive cisplatin IV over 1 hour on days 1-3, etoposide IV over 2
      hours on days 1-3, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim
      subcutaneously (SC) on day 6 or 7 of a 21-day cycle.

      INDUCTION CYCLE 4: Patients receive vincristine IV over 1 minute on day 1, doxorubicin IV
      over 1-15 minutes on days 1-2, cyclophosphamide IV over 1 hour on days 1-2, dinutuximab IV
      over 10-20 hours on days 2-5, and sargramostim SC on day 6 or 7 of a 21-day cycle.

      INDUCTION CYCLE 5: Patients receive cisplatin IV over 1 hour on days 1-3, etoposide IV over 2
      hours on days 1-3, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC on day 6
      or 7 of a 21-day cycle.

      Patients may undergo surgery after the fourth or fifth cycle of Induction at the discretion
      of treating doctor. Patients with stable disease or better tumor response at the end of
      Induction proceed to Consolidation. Consolidation treatment begins between 4 and 6 weeks from
      the start date of Induction chemotherapy cycle 5. For patients who have surgical resection
      delayed until after Induction chemotherapy cycle 5, Consolidation starts within 4 weeks from
      the date of surgery.

      CONSOLIDATION #1: Patients receive thiotepa IV over 2 hours on days -7 to -5 and
      cyclophosphamide IV over 1 hour on days -5 to -2. Patients then undergo autologous stem cell
      transplant (ASCT) on day 0.

      CONSOLIDATION #2: Patients receive melphalan IV over 30 minutes on days -7 to -5, etoposide
      IV over 24 hours on days -7 to -4, and carboplatin IV over 24 hours on days -7 to -4.
      Patients then undergo ASCT on day 0.

      RADIATION THERAPY: Beginning 42-80 days following Consolidation #2, patients receive external
      beam radiation therapy (EBRT) daily for up to 20 days.

      Patients then receive post-Consolidation therapy starting at least 1 week following radiation
      therapy.

      POST-CONSOLIDATION CYCLES 1-5: Patients receive sargramostim SC on days 1-14, dinutuximab IV
      over 10-20 hours on days 4-7, and isotretinoin orally (PO) twice daily (BID) on days 11-24.
      Treatment repeats every 28 days in the absence of disease progression or unacceptable
      toxicity.

      POST-CONSOLIDATION CYCLE 6: Patients receive isotretinoin PO BID on days 15-28 of a 28-day
      cycle.

      After completion of study treatment, patients are followed up at months 3, 6, 9, 12, 15, 18,
      24, 30, 36, 42, 48, 54, and 60.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Unacceptable Toxicity
time frame: Up to the first 5 cycles of treatment
description: Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.
measure: Percentage of Participants Who Are Feasibility "Failure"
time frame: Up to the first 5 cycles of treatment
description: Feasibility "failures" were defined as patients that did not receive >= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility "failure" rate together with a 95% confidence interval.
measure: Response Rate
time frame: Up to the first 5 cycles of treatment
description: Per the revised INRC, response is comprised by responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites were assessed using Response Evaluation Criteria in Solid Tumors and MIBG scans or FDG-PET scans if the tumor was MIBG non-avid. Bone marrow was assessed by histology or immunohistochemistry and cytology or immunocytology. Complete response (CR) - All components meet criteria for CR. Partial response (PR) - PR in at least one component and all other components are either CR, minimal disease (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with progressive disease (PD). Minor response (MR) - PR or CR in at least one component but at least one other component with stable disease; no component with PD. Stable disease (SD) - Stable disease in one component with no better than SD or NI in any other component; no component with PD. Progressive disease (PD) - Any component with PD.
measure: Event-free Survival
time frame: Up to 1 year
description: Per the revised INRC, progressive disease is: 1) > 20% increase in the longest diameter of the primary tumor, taking as reference the smallest sum and ¬> increase of 5 mm in longest dimension, 2) Any new soft tissue lesion detected by CT/MRI that is MIBG avid or FDG-PET avid, 3) Any new soft tissue lesion seen on CT/MRI that is biopsied and found to be neuroblastoma or ganglioneuroblastoma, 4) Any new bone site that is MIBG avid, 5) Any new bone site that is FDG-PET avid and has CT/MRI findings of tumor or is histologically neuroblastoma or ganglioneuroblastoma 6) A metastatic soft tissue site with > 20% increase in longest diameter, taking as reference the smallest sum on study, and with > 5mm in sum of diameters of target soft tissue lesions, 7) A relative MIBG score ¬> 1.2, 8) Bone marrow without tumor infiltration that becomes >5% tumor infiltration, 9) Bone marrow with tumor infiltration that increases by > 2-fold and has > 20% tumor infiltration on reassessment.
measure: Overall Survival
time frame: Up to 1 year
description: Kaplan-Meier method was used to estimate overall survival (OS). OS was defined as the time from study enrollment to death. 1-year OS is provided.
measure: Incidence of Naturally Occurring Anti-glycan Antibodies
time frame: Up to 5 years
description: The Incidence of Naturally Occurring Anti-glycan Antibodies was calculated, including placement of a 95% CI on the incidence. In addition, anti-glycan levels prior to the start of Induction therapy and prior to the start of post-Consolidation therapy was compared with Wilcoxon's signed-rank test for paired data.
measure: Incidence of Natural Killer (NK) Receptor NKp30 Isoforms
time frame: Up to 5 years
description: Assessed by calculating the incidence of NK receptor NKp30 isoforms, including placement of a 95% CI on the incidence.
measure: Response of Host Factors, Including Naturally Occurring Anti-glycan Antibodies, KIR/KIR-L Genotyping, Fc Receptor Genotyping, Human Anti-chimeric Antibodies (HACA)
time frame: Up to 5 years
description: Explored with Fisher's exact test for categorical and Wilcoxon rank-sum test for continuous host factors. Both the presence/absence and level of naturally occurring anti-glycan antibodies was considered. For the KIR/KIR-L analysis, patients were categorized as either matched or mismatched. Patients were grouped into one of the three genotype subgroups of Fc receptor genotyping for that analysis. The presence/absence of HACA, anti-idiotype, and pretreatment anti-therapeutic antibodies (PATA)/anti-allotype antibody was considered for the HACA analysis.
measure: Immune Environment (Gene Expression; Immune Effector Cells, Activities and Signaling Molecules; Immune Target Expression)
time frame: Up to 5 years
description: The incidence of NK receptor NKp30 isoforms was calculated, including placement of a 95% CI on each incidence rate. Summary statistics were generated for serum cytokine (IL6, CXCL9) levels and gene expression of circulating immune function cells.
measure: Levels of Circulating GD2 and Tumor Cell GD2 Expression
time frame: Up to 5 years
description: Assessed by exploring the relationship between response to treatment with > PR (response vs. non- response) with circulating GD2 levels, and GD2 tumor cell expression following therapy with a Wilcoxon rank-sum test. Changes from baseline were also analyzed.
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
arm group type: Experimental
description: See Detailed Description
intervention type: Procedure
intervention name: Autologous Hematopoietic Stem Cell Transplantation
description: Undergo ASCT
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: AHSCT
other name: Autologous
other name: Autologous Hematopoietic Cell Transplantation
other name: Autologous Stem Cell Transplant
other name: Autologous Stem Cell Transplantation
other name: Stem Cell Transplantation, Autologous
intervention type: Drug
intervention name: Carboplatin
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Blastocarb
other name: Carboplat
other name: Carboplatin Hexal
other name: Carboplatino
other name: Carboplatinum
other name: Carbosin
other name: Carbosol
other name: Carbotec
other name: CBDCA
other name: Displata
other name: Ercar
other name: JM-8
other name: Nealorin
other name: Novoplatinum
other name: Paraplatin
other name: Paraplatin AQ
other name: Paraplatine
other name: Platinwas
other name: Ribocarbo
intervention type: Drug
intervention name: Cisplatin
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Abiplatin
other name: Blastolem
other name: Briplatin
other name: CDDP
other name: Cis-diammine-dichloroplatinum
other name: Cis-diamminedichloridoplatinum
other name: Cis-diamminedichloro Platinum (II)
other name: Cis-diamminedichloroplatinum
other name: Cis-dichloroammine Platinum (II)
other name: Cis-platinous Diamine Dichloride
other name: Cis-platinum
other name: Cis-platinum II
other name: Cis-platinum II Diamine Dichloride
other name: Cismaplat
other name: Cisplatina
other name: Cisplatinum
other name: Cisplatyl
other name: Citoplatino
other name: Citosin
other name: Cysplatyna
other name: DDP
other name: Lederplatin
other name: Metaplatin
other name: Neoplatin
other name: Peyrone's Chloride
other name: Peyrone's Salt
other name: Placis
other name: Plastistil
other name: Platamine
other name: Platiblastin
other name: Platiblastin-S
other name: Platinex
other name: Platinol
other name: Platinol- AQ
other name: Platinol-AQ
other name: Platinol-AQ VHA Plus
other name: Platinoxan
other name: Platinum
other name: Platinum Diamminodichloride
other name: Platiran
other name: Platistin
other name: Platosin
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamide Monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Drug
intervention name: Dexrazoxane
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: 2, 6-Piperazinedione, 4,4'-propylenedi-, (P)- (8CI)
other name: 2,6-Piperazinedione, 4, 4'-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI)
other name: ADR-529
other name: ICRF-187
other name: Razoxane (+)-form
other name: Soluble ICRF (L-isomer)
intervention type: Biological
intervention name: Dinutuximab
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Ch 14.18UTC
other name: Ch14.18
other name: MOAB Ch14.18
other name: monoclonal antibody Ch14.18
other name: Unituxin
intervention type: Drug
intervention name: Doxorubicin
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Adriablastin
other name: Hydroxydaunomycin
other name: Hydroxyl Daunorubicin
other name: Hydroxyldaunorubicin
intervention type: Drug
intervention name: Etoposide
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Demethyl Epipodophyllotoxin Ethylidine Glucoside
other name: EPEG
other name: Lastet
other name: Toposar
other name: Vepesid
other name: VP 16
other name: VP 16-213
other name: VP-16
other name: VP-16-213
other name: VP16
intervention type: Radiation
intervention name: External Beam Radiation Therapy
description: Undergo EBRT
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Definitive Radiation Therapy
other name: EBRT
other name: External Beam Radiation
other name: External Beam Radiotherapy
other name: External Beam RT
other name: external radiation
other name: External Radiation Therapy
other name: external-beam radiation
other name: Radiation, External Beam
other name: Teleradiotherapy
other name: Teletherapy
other name: Teletherapy Radiation
intervention type: Drug
intervention name: Isotretinoin
description: Given PO
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: 13-cis retinoic acid
other name: 13-cis-Retinoate
other name: 13-cis-Retinoic Acid
other name: 13-cis-Vitamin A Acid
other name: 13-cRA
other name: Absorica
other name: Accure
other name: Accutane
other name: Amnesteem
other name: cis-Retinoic Acid
other name: Cistane
other name: Claravis
other name: Isotretinoinum
other name: Isotrex
other name: Isotrexin
other name: Myorisan
other name: Neovitamin A
other name: Neovitamin A Acid
other name: Oratane
other name: Retinoicacid-13-cis
other name: Ro 4-3780
other name: Ro-4-3780
other name: Roaccutan
other name: Roaccutane
other name: Roacutan
other name: Sotret
other name: ZENATANE
intervention type: Drug
intervention name: Melphalan
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Alanine Nitrogen Mustard
other name: CB-3025
other name: L-PAM
other name: L-Phenylalanine Mustard
other name: L-Sarcolysin
other name: L-Sarcolysin Phenylalanine mustard
other name: L-Sarcolysine
other name: Melphalanum
other name: Phenylalanine Mustard
other name: Phenylalanine Nitrogen Mustard
other name: Sarcoclorin
other name: Sarkolysin
other name: WR-19813
intervention type: Biological
intervention name: Sargramostim
description: Given SC
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: 23-L-Leucinecolony-Stimulating Factor 2
other name: DRG-0012
other name: Leukine
other name: Prokine
other name: rhu GM-CFS
other name: Sagramostim
other name: Sargramostatin
intervention type: Drug
intervention name: Thiotepa
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: 1,1',1''-Phosphinothioylidynetrisaziridine
other name: Girostan
other name: N,N', N''-Triethylenethiophosphoramide
other name: Oncotiotepa
other name: STEPA
other name: Tepadina
other name: TESPA
other name: Tespamin
other name: Tespamine
other name: Thio-Tepa
other name: Thiofosfamide
other name: Thiofozil
other name: Thiophosphamide
other name: Thiophosphoramide
other name: Thiotef
other name: Tifosyl
other name: TIO TEF
other name: Tio-tef
other name: Triethylene Thiophosphoramide
other name: Triethylenethiophosphoramide
other name: Tris(1-aziridinyl)phosphine sulfide
other name: TSPA
other name: WR 45312
intervention type: Drug
intervention name: Topotecan
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Hycamptamine
other name: Topotecan Lactone
intervention type: Drug
intervention name: Vincristine
description: Given IV
arm group label: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
other name: Leurocristine
other name: VCR
other name: Vincrystine
criteria: 
gender: All
minimum age: N/A
maximum age: 30 Years
healthy volunteers: No
last name: Sara M Federico
role: Principal Investigator
affiliation: Children's Oncology Group
facility: 
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country: Australia
country: New Zealand
country: United States
responsible party type: Sponsor
mesh term: Neuroblastoma
mesh term: Ganglioneuroblastoma
mesh term: Vitamin A
mesh term: Cyclophosphamide
mesh term: Melphalan
mesh term: Mechlorethamine
mesh term: Thiotepa
mesh term: Nitrogen Mustard Compounds
mesh term: Cisplatin
mesh term: Carboplatin
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Etoposide
mesh term: Vincristine
mesh term: Etoposide phosphate
mesh term: Daunorubicin
mesh term: Topotecan
mesh term: Tretinoin
mesh term: Podophyllotoxin
mesh term: Dinutuximab
mesh term: Dexrazoxane
mesh term: Razoxane
mesh term: 3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione
mesh term: Isotretinoin
mesh term: Sargramostim
sharing ipd: Yes
ipd description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
ipd url: https://grants.nih.gov/policy/sharing.htm
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 