xml: <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/NCT06013618</url>
    </required_header>
    <id_info>
      <org_study_id>3F8-RWS</org_study_id>
      <nct_id>NCT06013618</nct_id>
    </id_info>
    <brief_title>Clinical Analysis of Naxitamab (hu3F8) in the Treatment of Pediatric High Risk or Refractory/ Relapsed Neuroblastoma</brief_title>
    <official_title>Clinical Analysis of Naxitamab (hu3F8) in the Treatment of Pediatric High Risk or Refractory/ Relapsed Neuroblastoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sun Yat-sen University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Hainan General Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Sun Yat-sen University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is an prospective study to evaluate the safety and efficacy of naxitamab monotherapy or&#xD;
        combined with chemotherapy or combined with chemotherapy and checkpoint inhibitor in the&#xD;
        treatment of pediatric high-risk and refractory/relapsed neuroblastoma in Sun Yat-sen&#xD;
        University Cancer Center.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery,&#xD;
        radiotherapy and/or hematopoietic stem cell transplantation received axitamab and GM-CSF.&#xD;
        Patients with high-risk neuroblastoma treated by chemotherapy combined with surgery,&#xD;
        radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or&#xD;
        progression during treatment (refractory) received naxitamab and GM-CSF in combination with&#xD;
        irinotecan and temozolomide or naxitamab and GM-CSF in combination with irinotecan and&#xD;
        temozolomide and PD-1 antibody.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 19, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>ORR</measure>
      <time_frame>from start of naxitamab treatment to 1.5 years after EOT</time_frame>
      <description>The proportion of patients who achieved CR or PR</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>from start of naxitamab treatment to 1.5 years after EOT</time_frame>
      <description>The proportion of patients who achieved CR or PR or SD</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EFS</measure>
      <time_frame>from start of naxitamab treatment to 1.5 years after EOT</time_frame>
      <description>The time from from start of naxitamab treatment to disease progression, recurrence</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS</measure>
      <time_frame>from start of naxitamab treatment to 1.5 years after EOT</time_frame>
      <description>The time from from start of naxitamab treatment to death or loss of follow-up</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Neuroblastoma</condition>
    <arm_group>
      <arm_group_label>naxitamab and GM-CSF only</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Suitable for patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation. The treatment cycle is repeated every 4 weeks for a total of 5 courses, and discontinuation of nasetuzumab and GM-CSF should be considered if disease progression or unacceptable toxicity occurs.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Suitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Suitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Naxitamab monotherapy</intervention_name>
      <description>Naxitamab is administered on days 1, 3, and 5</description>
      <arm_group_label>naxitamab and GM-CSF only</arm_group_label>
      <other_name>hu3F8</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>GM-CSF</intervention_name>
      <description>Each treatment cycle is 28 days and is started with five days (days -4 to 0) of GM-CSF administered at 250 mcg/m2/day in advance of the start of naxitamab infusion. GM-CSF is thereafter administered at 500 mcg/m2/day on days 1 to 5.</description>
      <arm_group_label>naxitamab and GM-CSF only</arm_group_label>
      <other_name>Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Irinotecan</intervention_name>
      <description>Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.</description>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide</arm_group_label>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody</arm_group_label>
      <other_name>DNA topoisomerase I inhibitor</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Temozolomide</intervention_name>
      <description>Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.</description>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide</arm_group_label>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody</arm_group_label>
      <other_name>Temozolomide for Injection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Naxitamab in combination therapy</intervention_name>
      <description>Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10.</description>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide</arm_group_label>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody</arm_group_label>
      <other_name>hu3F8</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>GM-CSF with combination regimen</intervention_name>
      <description>GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10.</description>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide</arm_group_label>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody</arm_group_label>
      <other_name>Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sintilimab</intervention_name>
      <description>Sintilimab was administerd with 3mg/kg (max 200mg) on day 11 every 3 weeks.</description>
      <arm_group_label>naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody</arm_group_label>
      <other_name>PD-1 antibody</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          1)Confirmed diagnosis of high-risk NB 2)1 year of age or above 3)Patient or parent/guardian&#xD;
          must provide written informed consent to participate 4)If patient is sexually active, the&#xD;
          patient agrees to use effective contraception 5)Confirmed negative urine pregnancy test for&#xD;
          sexually active female of child-bearing potential (post-menarche)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Significant organ toxicity&#xD;
  &#xD;
            2. Known or suspected allergy or hypersensitivity to anti-GD2 antibodies or to GM-CSF or&#xD;
               its s components.&#xD;
  &#xD;
            3. Patient is pregnant, planning to become pregnant (while being treated with naxitamab)&#xD;
               or is currently breastfeeding&#xD;
  &#xD;
            4. Patient will undergo treatment with another investigational drug, whilst being treated&#xD;
               with naxitamab or has received another investigational drug within the 4 weeks prior&#xD;
               to commencing treatment with naxitamab&#xD;
  &#xD;
            5. Patient is either eligible and able to participate in or is currently participating in&#xD;
               an active interventional Y-mAbs sponsored clinical trial with naxitamab within the&#xD;
               indication applied for&#xD;
  &#xD;
            6. Patient is unable to comply with the naxitamab treatment or has a medical condition&#xD;
               that would potentially increase the severity of the toxicities experienced from&#xD;
               naxitamab treatment at the discretion of the treating physician&#xD;
  &#xD;
            7. Left ventricular ejection fraction of &lt;50% by echocardiography OR other clinically&#xD;
               relevant cardiac disorders at the discretion of the investigator&#xD;
  &#xD;
            8. Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise&#xD;
               intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry &lt;&#xD;
               94% and/or abnormal pulmonary function tests if these assessments are clinically&#xD;
               indicated&#xD;
  &#xD;
               Applicable for treatment with naxitamab in combination with GM-CSF only:&#xD;
  &#xD;
            9. Patient has active progression of the NB disease&#xD;
  &#xD;
           10. Patient has active NB disease at primary site or soft-tissue metastasis&#xD;
  &#xD;
           11. Patient has known CNS metastases when initiating naxitamab treatment&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>12 Months</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Yizhuo Zhang</last_name>
      <role>Study Chair</role>
      <affiliation>SunYat Sen University Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yizhuo Zhang, MD</last_name>
      <phone>+8618819241079</phone>
      <email>zhangyzh@sysucc.org.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Juan Wang</last_name>
      <phone>008687342660</phone>
      <email>wangjuan@sysucc.org.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Sun Yat-sen University Cancer Center</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510060</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yi-Zhuo Zhang, MD</last_name>
        <phone>18622221239</phone>
        <email>zhangyzh@sysucc.org.cn</email>
      </contact>
      <investigator>
        <last_name>Yi-Zhuo Zhang, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
      <investigator_full_name>Yizhuo Zhang</investigator_full_name>
      <investigator_title>Director</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neuroblastoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Irinotecan</mesh_term>
      <mesh_term>Topoisomerase I Inhibitors</mesh_term>
      <mesh_term>Temozolomide</mesh_term>
      <mesh_term>Molgramostim</mesh_term>
      <mesh_term>Sargramostim</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06013618
  org study id: 3F8-RWS
  nct id: NCT06013618
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This is an prospective study to evaluate the safety and efficacy of naxitamab monotherapy or
        combined with chemotherapy or combined with chemotherapy and checkpoint inhibitor in the
        treatment of pediatric high-risk and refractory/relapsed neuroblastoma in Sun Yat-sen
        University Cancer Center.
  Patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery,
        radiotherapy and/or hematopoietic stem cell transplantation received axitamab and GM-CSF.
        Patients with high-risk neuroblastoma treated by chemotherapy combined with surgery,
        radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or
        progression during treatment (refractory) received naxitamab and GM-CSF in combination with
        irinotecan and temozolomide or naxitamab and GM-CSF in combination with irinotecan and
        temozolomide and PD-1 antibody.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: ORR
  time frame: from start of naxitamab treatment to 1.5 years after EOT
  description: The proportion of patients who achieved CR or PR
  measure: DCR
  time frame: from start of naxitamab treatment to 1.5 years after EOT
  description: The proportion of patients who achieved CR or PR or SD
  measure: EFS
  time frame: from start of naxitamab treatment to 1.5 years after EOT
  description: The time from from start of naxitamab treatment to disease progression, recurrence
  measure: OS
  time frame: from start of naxitamab treatment to 1.5 years after EOT
  description: The time from from start of naxitamab treatment to death or loss of follow-up
  arm group label: naxitamab and GM-CSF only
  arm group type: Other
  description: Suitable for patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation. The treatment cycle is repeated every 4 weeks for a total of 5 courses, and discontinuation of nasetuzumab and GM-CSF should be considered if disease progression or unacceptable toxicity occurs.
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide
  arm group type: Other
  description: Suitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody
  arm group type: Other
  description: Suitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
  intervention type: Drug
  intervention name: Naxitamab monotherapy
  description: Naxitamab is administered on days 1, 3, and 5
  arm group label: naxitamab and GM-CSF only
  other name: hu3F8
  intervention type: Drug
  intervention name: GM-CSF
  description: Each treatment cycle is 28 days and is started with five days (days -4 to 0) of GM-CSF administered at 250 mcg/m2/day in advance of the start of naxitamab infusion. GM-CSF is thereafter administered at 500 mcg/m2/day on days 1 to 5.
  arm group label: naxitamab and GM-CSF only
  other name: Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor
  intervention type: Drug
  intervention name: Irinotecan
  description: Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody
  other name: DNA topoisomerase I inhibitor
  intervention type: Drug
  intervention name: Temozolomide
  description: Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody
  other name: Temozolomide for Injection
  intervention type: Drug
  intervention name: Naxitamab in combination therapy
  description: Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10.
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody
  other name: hu3F8
  intervention type: Drug
  intervention name: GM-CSF with combination regimen
  description: GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10.
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody
  other name: Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor
  intervention type: Drug
  intervention name: Sintilimab
  description: Sintilimab was administerd with 3mg/kg (max 200mg) on day 11 every 3 weeks.
  arm group label: naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody
  other name: PD-1 antibody
  criteria: 
  gender: All
  minimum age: 12 Months
  maximum age: N/A
  healthy volunteers: No
  last name: Yizhuo Zhang
  role: Study Chair
  affiliation: SunYat Sen University Cancer Center
  last name: Yizhuo Zhang, MD
  phone: +8618819241079
  email: zhangyzh@sysucc.org.cn
  last name: Juan Wang
  phone: 008687342660
  email: wangjuan@sysucc.org.cn
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Sun Yat-sen University
  investigator full name: Yizhuo Zhang
  investigator title: Director
  mesh term: Neuroblastoma
  mesh term: Irinotecan
  mesh term: Topoisomerase I Inhibitors
  mesh term: Temozolomide
  mesh term: Molgramostim
  mesh term: Sargramostim