<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/NCT02258815</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT:2009-015936-14</org_study_id>
    <nct_id>NCT02258815</nct_id>
  </id_info>
  <brief_title>CH14.18 1021 Antibody and IL2 After Haplo SCT in Children With Relapsed Neuroblastoma</brief_title>
  <official_title>Phase II Feasability Study Using ch14.18/CHO Antibody and Subcutaneous Interleukin 2 After Haploidentical Stem Cell Transplantation in Children With Relapsed Neuroblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Children's Hospital Tuebingen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Children's Hospital Tuebingen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m²) for five&#xD;
      consecutive days will be administered every 4 weeks, starting 60-180 days after previous&#xD;
      haploidentical stem cell transplantation.&#xD;
&#xD;
      Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants&#xD;
      will be premedicated with an intravenous antihistamine and ranitidine within approximately 30&#xD;
      minutes prior and during the infusion of the study agent Pain as an anticipated side effect&#xD;
      is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be&#xD;
      evaluated after 3 and 6 courses and after 1 year&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2010</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">December 2014</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>Success of treatment</measure>
    <time_frame>180 days</time_frame>
    <description>Primary endpoint is &quot;success of treatment&quot; defined as a patient receiving the full protocol treatment, still alive 180 days after treatment without progression and without unacceptable toxicity and acute GvHD &gt;= Grade III or extensive chronic GvHD.&#xD;
Thus, a composite variable is used as primary endpoint: Treatment success, is defined as a patients who did not experience&#xD;
unacceptable toxicities&#xD;
acute GvHD &gt;= Grade III or extensive chronic GvHD&#xD;
other toxicities that did not recover to &lt;= Grade 1 within 4 weeks or&#xD;
progressive disease after 6 cycles or&#xD;
deaths within treatment after SCT&#xD;
withdrawal due to other reasons</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti tumour responses</measure>
    <time_frame>1 year</time_frame>
    <description>• To evaluate the anti-tumour responses resulting from this immunotherapy regimen through clinical assessments (radiographic and clinical measurements, including bone marrow immunohistochemistry for those research participants with marrow involvement).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmakoinetics</measure>
    <time_frame>1 Year</time_frame>
    <description>* To evaluate pharmacokinetics of the ch14.18/CHO including analysis of cytokine levels in patients blood during administration. Antibody levels will be evaluated in determined intervals during Therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NK Cell aktivation and proliferation</measure>
    <time_frame>1 Year</time_frame>
    <description>* To evaluate changes in NK cell activation and proliferation (immunological monitoring) for additional support of potential Anti-tumor effect.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Neuroblastoma Recurrent</condition>
  <arm_group>
    <arm_group_label>ch14.18</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m² ) for five consecutive days will be administered every 4 weeks.&#xD;
Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants will be premedicated with an intravenous antihistamine and ranitidine within approximately 30 minutes prior and during the infusion of the study agent Pain as an anticipated side effect is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be evaluated after 3 and 6 courses and after 1 year.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ch14.18/CHO</intervention_name>
    <description>A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m² ) for five consecutive days will be administered every 4 weeks.&#xD;
Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants will be premedicated with an intravenous antihistamine and ranitidine within approximately 30 minutes prior and during the infusion of the study agent Pain as an anticipated side effect is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be evaluated after 3 and 6 courses and after 1 year.</description>
    <arm_group_label>ch14.18</arm_group_label>
    <other_name>ch14.18</other_name>
    <other_name>anti GD2 antibody</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Less than or equal to 21 years of age.&#xD;
&#xD;
          -  Histologically confirmed neuroblastoma.&#xD;
&#xD;
          -  Refractory to standard treatment (i.e. refractory disease) or relapse after previous&#xD;
             autologous or allogenic stem cell transplantation.&#xD;
&#xD;
          -  Patient has undergone haploidentical stem cell transplantation prior to antibody&#xD;
             infusion according to appendix IV at least 60 days prior to starting immunotherapy.&#xD;
&#xD;
          -  Serum glutamate pyruvate transaminase (SGPT) less than 2.5 times the upper limit of&#xD;
             normal for age and total bilirubin less than 2 times the upper limit of normal for&#xD;
             age. D-Dimers less than 2 times the upper limit of normal.&#xD;
&#xD;
        Creatinine clearance or radioisotope GFR greater than or equal to 40 ml/min/1.73m2.&#xD;
&#xD;
          -  Cardiac shortening fraction greater than or equal to 20% by echocardiogram.&#xD;
             Karnofsky/Lansky performance score (age appropriate) of greater than or equal to 50.&#xD;
&#xD;
          -  Females of childbearing potential must have a negative pregnancy test. Patients of&#xD;
             childbearing potential must agree to use an effective birth control method. Female&#xD;
             patients who are lactating must agree to stop breast-feeding.&#xD;
&#xD;
          -  Written informed consent is obtained, and for minors a written agreement by parents or&#xD;
             legal guardian.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval&#xD;
             &gt; 450 milliseconds).&#xD;
&#xD;
          -  Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm&#xD;
             disturbance.&#xD;
&#xD;
          -  Patients with significant psychiatric disabilities or uncontrolled seizure disorders.&#xD;
&#xD;
          -  Patients with active infections or active peptic ulcer, unless these conditions are&#xD;
             corrected or controlled.&#xD;
&#xD;
          -  Patients with acute GvHD Grade III or IV or extensive chronic GvHD.&#xD;
&#xD;
          -  Patients with clinically significant, symptomatic, pleural effusions.&#xD;
&#xD;
          -  Patients who have had major surgery, (i.e. laparotomy or thoracotomy) within the past&#xD;
             two weeks.&#xD;
&#xD;
          -  Patients who will more than 12 months post haploidentical stem cell transplantation at&#xD;
             the time of starting the first cycle of immunotherapy.&#xD;
&#xD;
          -  Prior administration of ch14.18 antibody after allogeneic stem cell transplantation&#xD;
             (prior administration after autologous transplantation will be acceptable)&#xD;
&#xD;
          -  HIV or Hepatitis B Surface (HBS) Ag positive. As presence of either may influence the&#xD;
             ability if the immune system to be stimulated by this treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Lang, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Tuebingen</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peter Lang, MD, PhD</last_name>
    <phone>+4970712983781</phone>
    <email>peter.lang@med.uni-tuebingen.de</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital Graz</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wolfgang Schwinger, MD, PhD</last_name>
      <phone>+43 31638512605</phone>
      <email>wolfgang.schwinger@medunigraz.at</email>
    </contact>
    <investigator>
      <last_name>Wolfgang Schwinger, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St. Anna Childrens Hospital</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ruth Ladenstein, MD, PhD</last_name>
      <phone>43 1 40470 3250</phone>
      <email>ruth.ladenstein@ccri.at</email>
    </contact>
    <investigator>
      <last_name>Ruth Ladenstein, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Greifswald</name>
      <address>
        <city>Greifswald</city>
        <zip>17475</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Holger Lode, MD, PhD</last_name>
      <phone>+49 3834866301</phone>
      <email>lode@uni-greifswald.de</email>
    </contact>
    <investigator>
      <last_name>Holger Lode, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Tuebingen</name>
      <address>
        <city>Tuebingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Lang, MD, PhD</last_name>
      <phone>+4970712983781</phone>
      <email>peter.lang@med.uni-tuebingen.de</email>
    </contact>
    <investigator>
      <last_name>Peter Lang, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Germany</country>
  </location_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>August 7, 2013</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>October 2, 2014</last_update_submitted>
  <last_update_submitted_qc>October 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 7, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Children's Hospital Tuebingen</investigator_affiliation>
    <investigator_full_name>Peter Lang</investigator_full_name>
    <investigator_title>Head of stem cell transplantation unit</investigator_title>
  </responsible_party>
  <keyword>pediatric</keyword>
  <keyword>haploidentical</keyword>
  <keyword>stem cell transplantation</keyword>
  <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>Dinutuximab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02258815
org study id: EudraCT:2009-015936-14
nct id: NCT02258815
lead sponsor: 
has dmc: Yes
A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m²) for five
      consecutive days will be administered every 4 weeks, starting 60-180 days after previous
      haploidentical stem cell transplantation.

      Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants
      will be premedicated with an intravenous antihistamine and ranitidine within approximately 30
      minutes prior and during the infusion of the study agent Pain as an anticipated side effect
      is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be
      evaluated after 3 and 6 courses and after 1 year
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Success of treatment
time frame: 180 days
description: Primary endpoint is "success of treatment" defined as a patient receiving the full protocol treatment, still alive 180 days after treatment without progression and without unacceptable toxicity and acute GvHD >= Grade III or extensive chronic GvHD.
Thus, a composite variable is used as primary endpoint: Treatment success, is defined as a patients who did not experience
unacceptable toxicities
acute GvHD >= Grade III or extensive chronic GvHD
other toxicities that did not recover to <= Grade 1 within 4 weeks or
progressive disease after 6 cycles or
deaths within treatment after SCT
withdrawal due to other reasons
measure: Anti tumour responses
time frame: 1 year
description: • To evaluate the anti-tumour responses resulting from this immunotherapy regimen through clinical assessments (radiographic and clinical measurements, including bone marrow immunohistochemistry for those research participants with marrow involvement).
measure: Pharmakoinetics
time frame: 1 Year
description: * To evaluate pharmacokinetics of the ch14.18/CHO including analysis of cytokine levels in patients blood during administration. Antibody levels will be evaluated in determined intervals during Therapy
measure: NK Cell aktivation and proliferation
time frame: 1 Year
description: * To evaluate changes in NK cell activation and proliferation (immunological monitoring) for additional support of potential Anti-tumor effect.
arm group label: ch14.18
arm group type: Experimental
description: A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m² ) for five consecutive days will be administered every 4 weeks.
Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants will be premedicated with an intravenous antihistamine and ranitidine within approximately 30 minutes prior and during the infusion of the study agent Pain as an anticipated side effect is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be evaluated after 3 and 6 courses and after 1 year.
intervention type: Drug
intervention name: ch14.18/CHO
description: A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m² ) for five consecutive days will be administered every 4 weeks.
Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants will be premedicated with an intravenous antihistamine and ranitidine within approximately 30 minutes prior and during the infusion of the study agent Pain as an anticipated side effect is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be evaluated after 3 and 6 courses and after 1 year.
arm group label: ch14.18
other name: ch14.18
other name: anti GD2 antibody
criteria: 
gender: All
minimum age: 1 Year
maximum age: 21 Years
healthy volunteers: No
last name: Peter Lang, MD, PhD
role: Principal Investigator
affiliation: University Hospital Tuebingen
last name: Peter Lang, MD, PhD
phone: +4970712983781
email: peter.lang@med.uni-tuebingen.de
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Austria
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University Children's Hospital Tuebingen
investigator full name: Peter Lang
investigator title: Head of stem cell transplantation unit
mesh term: Neuroblastoma
mesh term: Dinutuximab