<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/NCT02229266</url>
  </required_header>
  <id_info>
    <org_study_id>TUD-HINKL1-059</org_study_id>
    <nct_id>NCT02229266</nct_id>
  </id_info>
  <brief_title>Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With NK Cells in High-risk AML</brief_title>
  <acronym>HINKL</acronym>
  <official_title>Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With Haploidentical Natural Killer Cells in High-risk Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Technische Universität Dresden</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Technische Universität Dresden</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial investigates the efficacy of adoptive immunotherapy with haploidentical natural&#xD;
      killer cells compared to standard chemotherapy (after first complete remission) in patients&#xD;
      with a high-risk acute myeloid leukemia being older than 65 years of age and not eligible for&#xD;
      allogeneic transplantation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomised controlled phase-2 trial to determine the efficacy of adoptive immunotherapy with&#xD;
      haploidentical natural killer cells in high-risk acute myeloid leukemia&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    low recruitment rate&#xD;
  </why_stopped>
  <start_date>September 2015</start_date>
  <completion_date type="Actual">April 22, 2017</completion_date>
  <primary_completion_date type="Actual">April 22, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>2-year overall survival</measure>
    <time_frame>2 years after study inclusion</time_frame>
    <description>measure time of survival of each patiente up to 2 years after study inclusion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to relapse</measure>
    <time_frame>2 years after study inclusion</time_frame>
    <description>evaluate time to relapse for 2 years after study inclusion for each patient; calculate cumulative incidence of relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse-free survival</measure>
    <time_frame>2 years after study inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Yield and purity of NK cells (CD3-CD56+) after CD3 depletion and CD56 enrichment</measure>
    <time_frame>timepoint of application of NK cells</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NK cell analysis</measure>
    <time_frame>2 years after study inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical performance (ECOG score)</measure>
    <time_frame>2 years after study inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of GVHD</measure>
    <time_frame>6 months after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of (S)AEs</measure>
    <time_frame>5 weeks after start of treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>NK cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion of haploidentical NK cells after immunosuppression with cyclophosphamide and fludarabine, followed by immunostimulatory treatment with interleukin-2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Intervention</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 cycle of consolidation chemotherapy with high-dose cytarabine</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>NK cells</intervention_name>
    <arm_group_label>NK cells</arm_group_label>
    <other_name>CD3-negative/ CD56-positive NK cells from HLA-haploidentical family</other_name>
    <other_name>donors</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>1 cycle of consolidation chemotherapy with high-dose cytarabine</description>
    <arm_group_label>Control Intervention</arm_group_label>
    <other_name>chemotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed AML other than acute promyelocytic leukemia (APL) according to WHO&#xD;
             criteria&#xD;
&#xD;
          -  In AML defined by cytogenetic aberrations the proportion of blasts may be &lt;20%&#xD;
&#xD;
          -  Age ≥60 years&#xD;
&#xD;
          -  Clinical performance corresponding to ECOG score 0-2&#xD;
&#xD;
          -  High-risk karyotype&#xD;
&#xD;
          -  &lt;5% myeloblasts in bone marrow ≥21 days after beginning of most recent chemotherapy&#xD;
&#xD;
          -  maximal two preceding chemotherapy cycles&#xD;
&#xD;
          -  Potentially available haploidentical family donor (child/ sibling), willing and fit&#xD;
             for NK cell donation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  AML with favorable or intermediate risk cytogenetic features&#xD;
&#xD;
          -  Persistent aplasia following preceding chemotherapy&#xD;
&#xD;
          -  Relapsed or refractory AML&#xD;
&#xD;
          -  Known pre-existing autoimmune diseases&#xD;
&#xD;
          -  Any severe concomitant condition which makes it undesirable for the patient to&#xD;
             participate in the study&#xD;
&#xD;
          -  Any condition which could jeorpadize compliance of the protocol&#xD;
&#xD;
          -  Participation in another clinical trial during or within 4 weeks before study entry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martin Bornhäuser, Prof. Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Dresden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinikum Bayreuth</name>
      <address>
        <city>Bayreuth</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Chemnitz</name>
      <address>
        <city>Chemnitz</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Dresden</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.sal-aml.org</url>
    <description>Study Alliance Leukemia</description>
  </link>
  <link>
    <url>http://www.uniklinikum-dresden.de/das-klinikum/kliniken-polikliniken-institute/mk1</url>
    <description>Universitätsklinikum Dresden, Medizinische Klinik I</description>
  </link>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>August 10, 2021</last_update_submitted>
  <last_update_submitted_qc>August 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AML</keyword>
  <keyword>high-risk AML</keyword>
  <keyword>acute myeloid leukemia</keyword>
  <keyword>NK cells</keyword>
  <keyword>haploidentical natural killer cells</keyword>
  <keyword>immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</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/NCT02229266
org study id: TUD-HINKL1-059
nct id: NCT02229266
lead sponsor: 
collaborator: 
has dmc: Yes
The trial investigates the efficacy of adoptive immunotherapy with haploidentical natural
      killer cells compared to standard chemotherapy (after first complete remission) in patients
      with a high-risk acute myeloid leukemia being older than 65 years of age and not eligible for
      allogeneic transplantation
Randomised controlled phase-2 trial to determine the efficacy of adoptive immunotherapy with
      haploidentical natural killer cells in high-risk acute myeloid leukemia
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 2-year overall survival
time frame: 2 years after study inclusion
description: measure time of survival of each patiente up to 2 years after study inclusion
measure: Time to relapse
time frame: 2 years after study inclusion
description: evaluate time to relapse for 2 years after study inclusion for each patient; calculate cumulative incidence of relapse
measure: Relapse-free survival
time frame: 2 years after study inclusion
measure: Yield and purity of NK cells (CD3-CD56+) after CD3 depletion and CD56 enrichment
time frame: timepoint of application of NK cells
measure: NK cell analysis
time frame: 2 years after study inclusion
measure: Clinical performance (ECOG score)
time frame: 2 years after study inclusion
measure: Incidence and severity of GVHD
time frame: 6 months after start of treatment
measure: Incidence of (S)AEs
time frame: 5 weeks after start of treatment
arm group label: NK cells
arm group type: Experimental
description: Infusion of haploidentical NK cells after immunosuppression with cyclophosphamide and fludarabine, followed by immunostimulatory treatment with interleukin-2
arm group label: Control Intervention
arm group type: Active Comparator
description: 1 cycle of consolidation chemotherapy with high-dose cytarabine
intervention type: Biological
intervention name: NK cells
arm group label: NK cells
other name: CD3-negative/ CD56-positive NK cells from HLA-haploidentical family
other name: donors
intervention type: Drug
intervention name: Cytarabine
description: 1 cycle of consolidation chemotherapy with high-dose cytarabine
arm group label: Control Intervention
other name: chemotherapy
criteria: 
gender: All
minimum age: 60 Years
maximum age: 99 Years
healthy volunteers: No
last name: Martin Bornhäuser, Prof. Dr. med.
role: Principal Investigator
affiliation: Universitätsklinikum Dresden
facility: 
facility: 
facility: 
country: Germany
url: http://www.sal-aml.org
description: Study Alliance Leukemia
url: http://www.uniklinikum-dresden.de/das-klinikum/kliniken-polikliniken-institute/mk1
description: Universitätsklinikum Dresden, Medizinische Klinik I
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine