<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/NCT03300492</url>
  </required_header>
  <id_info>
    <org_study_id>Haplo-NK-DLI for AML/MDS</org_study_id>
    <nct_id>NCT03300492</nct_id>
  </id_info>
  <brief_title>Expanded Natural Killer Cells Following Haploidentical HSCT for AML/MDS</brief_title>
  <official_title>A Phase I/II Single Center Study to Assess the Safety, Tolerability and Feasibility of Pre-emptive Immunotherapy With in Vitro Expanded Natural Killer Cells in Patients Treated With Haplo-HSCT for AML/MDS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study examines the application of expanded natural killer cells (NK cells) following&#xD;
      haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) for AML or&#xD;
      MDS. Haplo-HSCT is a preferred treatment option for patients with AML or MDS without a&#xD;
      HLA-matched donor. With administration of cyclophosphamide post-transplant , the safety of&#xD;
      the procedure is similar to a HSCT from a HLA-identical donor. Relapse of AML/MDS represents&#xD;
      a serious problem following haplo-HSCT. NK cells are immune cells able to destroy tumor&#xD;
      cells. Their potency has been established particularly in the setting of a haplo-HSCT. In the&#xD;
      current study, study participants undergoing haplo-HSCT will receive expanded NK cells from&#xD;
      their respective stem-cell donors following haplo-HSCT. The primary goal of the study is to&#xD;
      establish the safety and feasibility of this approach. In addition, the activity of the NK&#xD;
      cells will be examined.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 12, 2018</start_date>
  <completion_date type="Anticipated">January 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2023</primary_completion_date>
  <phase>Phase 1/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>
    <intervention_model_description>Prospective, single center, open-label, single arm study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and severity of adverse events including GvHD and infections.</measure>
    <time_frame>1 year following haplo HSCT</time_frame>
    <description>As defined by the CTCAE version 4.03 and the NIH Scoring of GvHD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>1 year following haplo HSCT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of AML/MDS-EB complete morphological and molecular remission (CR) at day + 30, + 90, +180 and 1 year post allo-HSCT</measure>
    <time_frame>1 year following haplo HSCT</time_frame>
    <description>rejection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of graft rejection</measure>
    <time_frame>1 year following haplo HSCT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of NK cells given per kg body weight</measure>
    <time_frame>30 days following haplo-HSCT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of NK-DLI infusions applied</measure>
    <time_frame>30 days following haplo-HSCT</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>NK-DLI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Preemptive immunotherapy with ex vivo expanded NK cells on days&#xD;
+10, +15 and +20 with increasing NK cell doses following haplo-HSCT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>NK-DLI</intervention_name>
    <description>Application of three infusions of ex vivo expanded NK cells on days&#xD;
+10, +15 and +20 with increasing NK cell doses (1x107/kg, 1x108/kg and the remaining cells up to 1x109/kg) following haplo-HSCT. Maximal cumulative T-cell dose is fixed at &lt;1x105/kg.</description>
    <arm_group_label>NK-DLI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patient:&#xD;
&#xD;
          -  &gt;18 years of age&#xD;
&#xD;
          -  No HLA-matched related or unrelated donor available&#xD;
&#xD;
          -  AML or MDS-EB with indication for a haplo-HSCT according to the guidelines of the&#xD;
             University Hospital Basel Stem Cell Transplant Team&#xD;
&#xD;
          -  Judged by the transplant physicians to have adequate organ function and no&#xD;
             contraindications to haplo-HSCT&#xD;
&#xD;
          -  Available related haploidentical donor&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Donor:&#xD;
&#xD;
          -  &gt;18 years old, haploidentical parent, sibling or other relative&#xD;
&#xD;
          -  Donor suitable for cell donation and apheresis according to standard criteria&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patient:&#xD;
&#xD;
          -  APL diagnosis&#xD;
&#xD;
          -  Presence of relevant (mean fluorescence intensity &gt;2000) donor-specific anti-HLA&#xD;
             antibodies&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Necessity of immunosuppression apart from GvHD prophylaxis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Donor:&#xD;
&#xD;
        • Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jakob Passweg, Prof. MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Basel, Basel Switzerland</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Matyas Ecsedi, MD-PhD</last_name>
    <phone>+41612652525</phone>
    <email>matyas.ecsedi@usb.ch</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital Basel</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matyas Ecsedi, MD-PhD</last_name>
      <phone>+41612652525</phone>
      <email>matyas.ecsedi@usb.ch</email>
    </contact>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 30, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>November 28, 2022</last_update_submitted>
  <last_update_submitted_qc>November 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Natural Killer cells</keyword>
  <keyword>NK cells</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>haploidentical hematopoietic stem cell transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03300492
org study id: Haplo-NK-DLI for AML/MDS
nct id: NCT03300492
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study examines the application of expanded natural killer cells (NK cells) following
      haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) for AML or
      MDS. Haplo-HSCT is a preferred treatment option for patients with AML or MDS without a
      HLA-matched donor. With administration of cyclophosphamide post-transplant , the safety of
      the procedure is similar to a HSCT from a HLA-identical donor. Relapse of AML/MDS represents
      a serious problem following haplo-HSCT. NK cells are immune cells able to destroy tumor
      cells. Their potency has been established particularly in the setting of a haplo-HSCT. In the
      current study, study participants undergoing haplo-HSCT will receive expanded NK cells from
      their respective stem-cell donors following haplo-HSCT. The primary goal of the study is to
      establish the safety and feasibility of this approach. In addition, the activity of the NK
      cells will be examined.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Prospective, single center, open-label, single arm study
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence and severity of adverse events including GvHD and infections.
time frame: 1 year following haplo HSCT
description: As defined by the CTCAE version 4.03 and the NIH Scoring of GvHD.
measure: Progression-free survival (PFS)
time frame: 1 year following haplo HSCT
measure: Incidence of AML/MDS-EB complete morphological and molecular remission (CR) at day + 30, + 90, +180 and 1 year post allo-HSCT
time frame: 1 year following haplo HSCT
description: rejection.
measure: Incidence of graft rejection
time frame: 1 year following haplo HSCT
measure: Number of NK cells given per kg body weight
time frame: 30 days following haplo-HSCT
measure: Number of NK-DLI infusions applied
time frame: 30 days following haplo-HSCT
arm group label: NK-DLI
arm group type: Experimental
description: Preemptive immunotherapy with ex vivo expanded NK cells on days
+10, +15 and +20 with increasing NK cell doses following haplo-HSCT.
intervention type: Other
intervention name: NK-DLI
description: Application of three infusions of ex vivo expanded NK cells on days
+10, +15 and +20 with increasing NK cell doses (1x107/kg, 1x108/kg and the remaining cells up to 1x109/kg) following haplo-HSCT. Maximal cumulative T-cell dose is fixed at <1x105/kg.
arm group label: NK-DLI
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jakob Passweg, Prof. MD
role: Principal Investigator
affiliation: University Hospital Basel, Basel Switzerland
last name: Matyas Ecsedi, MD-PhD
phone: +41612652525
email: matyas.ecsedi@usb.ch
facility: 
status: Recruiting
contact: 
country: Switzerland
responsible party type: Sponsor
mesh term: Myelodysplastic Syndromes
sharing ipd: No