<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/NCT01734304</url>
  </required_header>
  <id_info>
    <org_study_id>2010-022446-24</org_study_id>
    <nct_id>NCT01734304</nct_id>
  </id_info>
  <brief_title>DC Vaccination for Postremission Therapy in AML</brief_title>
  <official_title>Active Immunotherapy of Patients With Acute Myeloid Leukemia Using Autologous Dendritic Cells Transfected With RNA Encoding Leukemia-associated Antigens</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ludwig-Maximilians - University of Munich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ludwig-Maximilians - University of Munich</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to determine the feasibility and safety of an autologous DC&#xD;
      immunotherapy in patients with AML of non-favorable risk profile.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients ≥ 18 years of either gender with AML of non-favorable risk profile in CR or CRi not&#xD;
      being eligible for allogeneic stem cell transplantation will receive as intradermal&#xD;
      injections at two different sites up to ten immunotherapies with autologous DCs presenting&#xD;
      two leukemia-associated antigens and one CMV antigen conserved in cryomedium over a time span&#xD;
      of 26 weeks. Phase I will test the safety and toxicity in a small group of patients (n=6).&#xD;
      After at least four vaccinations of three patients, the safety and toxicity data will be&#xD;
      presented to the Data safety monitoring board (DSMB). Only after the DSMB has no objectives&#xD;
      against the continuation of the trial, further patients will be included into the trial.&#xD;
      Again, after three more patients, receiving a minimum of four vaccines, clinical data will be&#xD;
      presented to the DSMB, and phase I will be terminated. The decision for continuation of the&#xD;
      trial will be done by the DSMB. If there are no objectives by the DSMB, the trial will&#xD;
      continue and evaluation will be started in a larger group of patients (n=14). During the&#xD;
      phase II trial, safety and toxicity will be evaluated in a larger co-hort of patients).&#xD;
      Besides, preliminary assessment of efficacy will be performed including induction of&#xD;
      immunological responses to leukemia associated antigens as well as to a viral antigen (CMV),&#xD;
      MRD control, time to progression of disease and ECOG performance status.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2013</start_date>
  <completion_date type="Actual">September 30, 2018</completion_date>
  <primary_completion_date type="Actual">March 31, 2018</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>% of grade I/II and grade III/IV toxicities</measure>
    <time_frame>30 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immune responses to applied antigens</measure>
    <time_frame>30 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Control of minimal residual disease</measure>
    <time_frame>30 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression of disease</measure>
    <time_frame>30 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ECOG performance status</measure>
    <time_frame>30 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>DC vaccination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DC vaccination for postremission therapy in AML</intervention_name>
    <description>Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65</description>
    <arm_group_label>DC vaccination</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients male or female, age ≥ 18 years, biological age ≤ 75 years&#xD;
&#xD;
          -  Patients with AML of non-favorable risk profile or with AML and sole NPM1 mutation and&#xD;
             confirmed increase of MRD load as detected by RQ-PCR (in two measurements at least&#xD;
             four weeks apart)&#xD;
&#xD;
          -  CR or CRi after intensive induction chemotherapy (TAD, HAM, sHAM, 3+7 anthracycline +&#xD;
             cytarabine regimen, or equivalent)&#xD;
&#xD;
          -  Negative HIV test, negative hepatitis B and C test&#xD;
&#xD;
          -  Negative pregnancy test in women of childbearing potential&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients suitable for allogeneic HSCT (indication for allogeneic HSCT, adequate donor,&#xD;
             no contraindication for allogeneic HSCT)&#xD;
&#xD;
          -  Patients with AML with favorable risk profile:&#xD;
&#xD;
          -  APL (AML M3)&#xD;
&#xD;
          -  inv(16), t(16;16), or del(16) as sole anomaly&#xD;
&#xD;
          -  t(8;21) as sole anomaly&#xD;
&#xD;
          -  biallelic CEBPA mutation as sole anomaly&#xD;
&#xD;
          -  NPM1 mutation as sole anomaly, unless with confirmed increase of MRD load&#xD;
&#xD;
          -  Prior allogeneic HSCT&#xD;
&#xD;
          -  Anemia (Hb &lt; 9,0 mg/dl)&#xD;
&#xD;
          -  Leukopenia (&lt; 4,0 G/l)&#xD;
&#xD;
          -  Transfusion refractory thrombocytopenia (&lt; 30 G/l platelets despite adequate number of&#xD;
             transfusions)&#xD;
&#xD;
          -  Active clinically relevant autoimmune disease&#xD;
&#xD;
          -  Active immunodeficiency syndromes&#xD;
&#xD;
          -  Known allergy to GM-CSF, TNF, IFN-γ, IL-4, IL-1 beta, PGE2, R848, Human AB Serum,&#xD;
             DMSO, HSA&#xD;
&#xD;
          -  Continuous therapy with corticosteroids or other immunosuppressive drugs during the&#xD;
             trial&#xD;
&#xD;
          -  Present substance abuse or any other factor that could limit the subject's ability to&#xD;
             comply with study procedures&#xD;
&#xD;
          -  Severe organ dysfunction:&#xD;
&#xD;
          -  Creatinine &gt; 2,5 mg/ml&#xD;
&#xD;
          -  Bilirubin &gt; 3,0 mg/ml&#xD;
&#xD;
          -  ALAT and ASAT &gt; 3 x upper normal limit&#xD;
&#xD;
          -  Respiratory insufficiency with pO2 &lt; 60 mmHg&#xD;
&#xD;
          -  Clinically relevant coronary heart disease of ventricular arrhythmia, congestive heart&#xD;
             failure &gt; grade II NYHA&#xD;
&#xD;
          -  Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or&#xD;
             investigational product administration or may interfere with the interpretation of&#xD;
             study results and, in the judgment of the investigator, would make the subject&#xD;
             inappropriate for entry into this study&#xD;
&#xD;
          -  Simultaneous participation in another clinical trial or participation in any clinical&#xD;
             trial involving an investigational medicinal product within 30 days prior to written&#xD;
             informed consent for this trial&#xD;
&#xD;
        Exclusion criteria regarding special restrictions for females:&#xD;
&#xD;
          -  Current or planned pregnancy or nursing women&#xD;
&#xD;
          -  Females of childbearing potential, who are not using and not willing to use medically&#xD;
             reliable methods of contraception for the entire study duration and at least 3 months&#xD;
             thereafter (such as oral, injectable, or im-plantable contraceptives, or intrauterine&#xD;
             contraceptive devices) unless they are surgically sterilized/hysterectomized or there&#xD;
             are any other criteria considered sufficiently reliable by the investigator in&#xD;
             individual cases&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marion Subklewe, PD Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Medicine III; Hospital of the University of Munich,</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital of the University of Munich, LMU; Department od Medicine III</name>
      <address>
        <city>Munich</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>October 17, 2012</study_first_submitted>
  <study_first_submitted_qc>November 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>October 10, 2018</last_update_submitted>
  <last_update_submitted_qc>October 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ludwig-Maximilians - University of Munich</investigator_affiliation>
    <investigator_full_name>PD Dr. Marion Subklewe</investigator_full_name>
    <investigator_title>Prof. Dr. med. Marion Subklewe</investigator_title>
  </responsible_party>
  <keyword>vaccination</keyword>
  <keyword>postremission therapy</keyword>
  <keyword>acute myeloid leukemia</keyword>
  <keyword>dendritic cells</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>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT01734304
org study id: 2010-022446-24
nct id: NCT01734304
lead sponsor: 
has dmc: Yes
The aim of this study is to determine the feasibility and safety of an autologous DC
      immunotherapy in patients with AML of non-favorable risk profile.
Patients ≥ 18 years of either gender with AML of non-favorable risk profile in CR or CRi not
      being eligible for allogeneic stem cell transplantation will receive as intradermal
      injections at two different sites up to ten immunotherapies with autologous DCs presenting
      two leukemia-associated antigens and one CMV antigen conserved in cryomedium over a time span
      of 26 weeks. Phase I will test the safety and toxicity in a small group of patients (n=6).
      After at least four vaccinations of three patients, the safety and toxicity data will be
      presented to the Data safety monitoring board (DSMB). Only after the DSMB has no objectives
      against the continuation of the trial, further patients will be included into the trial.
      Again, after three more patients, receiving a minimum of four vaccines, clinical data will be
      presented to the DSMB, and phase I will be terminated. The decision for continuation of the
      trial will be done by the DSMB. If there are no objectives by the DSMB, the trial will
      continue and evaluation will be started in a larger group of patients (n=14). During the
      phase II trial, safety and toxicity will be evaluated in a larger co-hort of patients).
      Besides, preliminary assessment of efficacy will be performed including induction of
      immunological responses to leukemia associated antigens as well as to a viral antigen (CMV),
      MRD control, time to progression of disease and ECOG performance status.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: % of grade I/II and grade III/IV toxicities
time frame: 30 weeks
measure: Immune responses to applied antigens
time frame: 30 weeks
measure: Control of minimal residual disease
time frame: 30 weeks
measure: Time to progression of disease
time frame: 30 weeks
measure: ECOG performance status
time frame: 30 weeks
arm group label: DC vaccination
arm group type: Experimental
description: Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65
intervention type: Biological
intervention name: DC vaccination for postremission therapy in AML
description: Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65
arm group label: DC vaccination
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Marion Subklewe, PD Dr
role: Principal Investigator
affiliation: Department of Medicine III; Hospital of the University of Munich,
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Ludwig-Maximilians - University of Munich
investigator full name: PD Dr. Marion Subklewe
investigator title: Prof. Dr. med. Marion Subklewe
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
sharing ipd: Undecided