<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/NCT01686334</url>
  </required_header>
  <id_info>
    <org_study_id>CCRG12-001</org_study_id>
    <nct_id>NCT01686334</nct_id>
  </id_info>
  <brief_title>Efficacy Study of Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia in Remission</brief_title>
  <acronym>WIDEA</acronym>
  <official_title>Wilms' Tumor (WT1) Antigen-targeted Dendritic Cell Vaccination to Prevent Relapse in Adult Patients With Acute Myeloid Leukemia: a Multicenter Randomized Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zwi Berneman</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kom Op Tegen Kanker</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stichting tegen Kanker</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Research Foundation - Flanders (FWO: Fonds Wetenschappelijk Onderzoek)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Antwerp</source>
  <brief_summary>
    <textblock>
      The primary aim of this innovative immunotherapeutic study is to determine whether the&#xD;
      antileukemic effects seen in our previous phase I/II study can be confirmed in a large cohort&#xD;
      of patients and whether dendritic cell vaccination can significantly prevent relapse and&#xD;
      increase survival of acute myeloid leukemia (AML) patients by eradicating minimal residual&#xD;
      disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Together with the Transplant Committee of the Belgian Hematological Society (BHS), we will&#xD;
      perform a multicenter randomized open-label phase II clinical study in 130 patients with&#xD;
      acute myeloid leukemia (AML). Adult patients (&gt; 18 years) with AML who have entered&#xD;
      morphological CR or CRi after (1) intensive chemotherapy (i.e (i) at least one cycle of&#xD;
      induction and one cycle of consolidation chemotherapy or (ii) one to two cycles of CPX-351&#xD;
      induction treatment and up to two cycles of CPX-351 consolidation treatment) or (2)&#xD;
      low-intensity chemotherapy (i.e (iii) at least two cycles to maximum six cycles of&#xD;
      hypomethylating agents whether or not combined with venetoclax or (iv) at least two cycles to&#xD;
      maximum six cycles of low-dose cytarabine combined with venetoclax); and fulfilling all other&#xD;
      eligibility criteria will be randomized to be vaccinated with dendritic cells or to receive&#xD;
      regular follow-up care. After randomization, patients receiving low-intensity chemotherapy&#xD;
      are allowed to continue this treatment in combination with DC vaccination or the follow-up&#xD;
      care. The primary aim of this innovative immunotherapeutic study is to determine whether the&#xD;
      antileukemic effects seen in our previous phase I/II study can be confirmed in a large cohort&#xD;
      of patients and whether dendritic cell vaccination can significantly prevent relapse and&#xD;
      increase survival of AML patients by eradicating minimal residual disease. Patients will be&#xD;
      recruited at 8 different centers in Belgium. Recruitment will start in the second half of&#xD;
      2013 and will last for 10 years or until 130 efficacy-evaluable AML patients are included. In&#xD;
      the interventional group, 65 patients will be treated during two years with autologous&#xD;
      dendritic cells loaded by messenger RNA electroporation with the Wilms' tumor antigen (WT1).&#xD;
      The dendritic cell therapy product will be generated and generally administered in the&#xD;
      coordinating center, which is the Antwerp University Hospital, more specifically the Center&#xD;
      for Cell Therapy and Regenerative Medicine (CCRG) and the Division of Hematology, both headed&#xD;
      by Prof. Zwi Berneman. After inclusion of 130 efficacy-evaluable patients, relapse rate,&#xD;
      relapse-free survival and overall survival analysis will be performed. Tumor marker levels&#xD;
      and immune activation will also be monitored to compare the 2 groups at a molecular and&#xD;
      immunological level. General and disease-specific quality of life will be evaluated using&#xD;
      quality of life questionnaires at regular time points.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>October 2012</start_date>
  <primary_completion_date type="Anticipated">July 2024</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>Overall survival</measure>
    <time_frame>At study completion, an average of 5 year</time_frame>
    <description>The primary objective of this randomized phase II clinical study is to determine the effect of WT1-targeted dendritic cell vaccination on overall survival in adult AML patients at very high risk of relapse and in complete remission.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relapse rate</measure>
    <time_frame>At study completion, an average of 5 year</time_frame>
    <description>to determine the effect of WT1-targeted dendritic cell vaccination on relapse rate in adult AML patients at very high risk of relapse and in complete remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>relapse-free survival</measure>
    <time_frame>At study completion, an average of 5 year</time_frame>
    <description>to determine the effect of WT1-targeted dendritic cell vaccination on relapse-free survival in adult AML patients at very high risk of relapse and in complete remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in WT1 mRNA levels in peripheral blood</measure>
    <time_frame>Through study completion, at every vaccination during 2 years</time_frame>
    <description>Efficacy assessment will also be performed on a molecular level. To this end, peripheral blood samples will be obtained from participants in both study groups (vaccine group and control group) and analyzed by qRT-PCR for WT1 expression, which is a promising molecular biomarker in AML.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune activation</measure>
    <time_frame>After the 4th DC vaccine</time_frame>
    <description>This study aims to examine the presence of leukemia-specific immune responses in AML patients in remission and to investigate whether they can be induced or increased in these patients by WT1 mRNA-electroporated DC vaccination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>General and disease-specific quality of life</measure>
    <time_frame>At study completion, an average of 5 year</time_frame>
    <description>Patients will be asked to fill out general and disease-specific quality of life questionnaires to assess changes in general and disease-specific quality of life during the study at regular time points</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Tertiary: Safety</measure>
    <time_frame>At study completion, an average of 5 year</time_frame>
    <description>To corroborate the safety of WT1 mRNA-electroporated DC vaccination in adult patients with AML. Safety will be assessed at every visit by adverse event reporting and clinical laboratory tests.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory: Effect of low-intensity chemotherapy</measure>
    <time_frame>At study completion, an average of 5 year</time_frame>
    <description>To evaluate the effect of low-intensity chemotherapy on the primary and secondary objectives.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">130</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>DC vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination with autologous WT1 mRNA-electroporated DCs plus follow-up care. Patients receiving low-intensity chemotherapy are allowed to continue this treatment in combination with DC vaccination.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Follow-up care. Patients receiving low-intensity chemotherapy are allowed to continue this treatment during the follow-up care</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DC vaccine</intervention_name>
    <description>Autologous WT1 mRNA-electroporated DCs</description>
    <arm_group_label>DC vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of acute myeloid leukemia (AML) according to the 2008 criteria of the World&#xD;
             Health Organization (WHO).&#xD;
&#xD;
               -  all French-American-British (FAB) subtypes, except:&#xD;
&#xD;
                  - M3 (acute promyelocytic leukemia)&#xD;
&#xD;
               -  all cases of de novo AML or secondary AML with ≥ 20 % blasts in peripheral blood&#xD;
                  and/or bone marrow, except:&#xD;
&#xD;
                    -  AML secondary to myeloproliferative neoplasms (MPN)&#xD;
&#xD;
                    -  AML secondary to exposure of leukemogenic agents (t-AML) unless treated with&#xD;
                       CPX-351 chemotherapy or hypomethylating agents combined with venetoclax.&#xD;
&#xD;
          -  Completion of one of the following treatment options:&#xD;
&#xD;
               -  I) Intensive chemotherapy:&#xD;
&#xD;
                    -  (1) at least one cycle of induction chemotherapy and one cycle of&#xD;
                       consolidation chemotherapy (low-dose cytarabine as consolidation therapy is&#xD;
                       allowed) OR&#xD;
&#xD;
                    -  (2) one to two cycles of CPX-351 induction treatment and up to two cycles of&#xD;
                       CPX-351 consolidation treatment OR&#xD;
&#xD;
               -  II) Low-intensity chemotherapy:&#xD;
&#xD;
                    -  (3) at least two cycles to maximum six cycles of hypomethylating agents&#xD;
                       whether or not combined with venetoclax OR&#xD;
&#xD;
                    -  (4) at least two cycles to maximum six cycles of low-dose cytarabine&#xD;
                       combined with venetoclax;&#xD;
&#xD;
               -  resulting in:&#xD;
&#xD;
                    -  morphological complete remission (CR), i.e. bone marrow blast count &lt;5% with&#xD;
                       neutrophil count &gt;1000 cells/µL and platelet count &gt;100,000 cells/µL OR&#xD;
&#xD;
                    -  morphological complete remission with incomplete blood recovery (CRi), i.e.&#xD;
                       bone marrow blast count &lt;5% with neutrophil count &lt;1000 cells/µL or platelet&#xD;
                       count &lt;100,000 cells/µL.&#xD;
&#xD;
        For the purpose of this study protocol, platelet count must be &gt;50,000 cells/µL.&#xD;
&#xD;
          -  Interval between the completion of the last intensive chemotherapy administration (in&#xD;
             case of low-intensity chemotherapy: last cycle (min. 2 to max. 6 cycles) before&#xD;
             achieving CR or CRi) and the start of vaccination (or the start of follow-up in case&#xD;
             of the control arm): 6 weeks (minimum) and 16 weeks (maximum) (in case of&#xD;
             low-intensity chemotherapy: maximum 10 weeks).&#xD;
&#xD;
          -  Adult (≥ 18 years) at very high risk of relapse according to:&#xD;
&#xD;
               -  Age ≥ 60 years, and/or&#xD;
&#xD;
               -  Adverse biological features (e.g. adverse cytogenetics, adverse morphological&#xD;
                  features, adverse molecular features, hyperleukocytosis (&gt; 100000 cells/µL)), and&#xD;
&#xD;
               -  Ineligible for or unwilling to receive hematopoietic stem cell transplantation.&#xD;
&#xD;
          -  WHO performance status: grade 0, 1 or 2 at the time of enrollment. For definition of&#xD;
             performance status, see: http://www.ecog.org/general/perf_stat.html&#xD;
&#xD;
          -  Absence of any psychological, familial, sociological, geographical or physical&#xD;
             condition potentially hampering compliance with the study protocol and follow-up&#xD;
             schedule; those conditions should be discussed with the patient before study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in any other interventional clinical trial during the study period.&#xD;
&#xD;
          -  History or concomitant presence of any other malignancy, except for:&#xD;
&#xD;
               -  non-melanoma skin cancer&#xD;
&#xD;
               -  carcinoma in situ of the cervix&#xD;
&#xD;
               -  any other effectively treated malignancy that has been in remission for &gt;5 years&#xD;
                  or that is highly likely to be cured at the time of enrollment.&#xD;
&#xD;
          -  Concomitant presence of any immunosuppressive disease (e.g. HIV) or any active&#xD;
             autoimmune condition, except for vitiligo.&#xD;
&#xD;
          -  Concomitant use of systemic corticosteroids in immunosuppressive doses (&gt;1 mg/kg/day&#xD;
             of prednisone, or equivalent dose for other corticosteroid preparations) or any other&#xD;
             immunosuppressive agent. A minimum of 4 weeks must have elapsed between the last dose&#xD;
             of immunosuppressive therapy and the first vaccination. Topical corticosteroids are&#xD;
             permitted, except if applied at the sites of DC injection.&#xD;
&#xD;
          -  Pregnant or breast-feeding&#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>Zwi Berneman, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital, Antwerp</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Evelien LJ Smits, MSc, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universiteit Antwerpen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sébastien Anguille, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Antwerp</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ann Van de Velde, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Antwerp</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zwi N Berneman, MD, PhD</last_name>
    <phone>+32 3 8213780</phone>
    <email>zwi.berneman@uza.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ann Van de Velde, MD, PhD</last_name>
    <phone>+32 3 8213916</phone>
    <email>ann.vandevelde@uza.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>ZNA Stuivenberg</name>
      <address>
        <city>Antwerp</city>
        <zip>2060</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Local Investigator: Dimitri Breems, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Antwerp University Hospital</name>
      <address>
        <city>Antwerp</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Zwi N Berneman, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Brussels</name>
      <address>
        <city>Brussels</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Local Investigator: Rik Schots, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Brussel</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Local Investigator: Violaine Havelange, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ghent University Hospital</name>
      <address>
        <city>Ghent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Local Investigator: Tessa Kerre, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Liège</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Local Investigator: Yves Beguin, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AZ Delta</name>
      <address>
        <city>Roeselare</city>
        <zip>8800</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Local Investigator: Dries Deeren, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Mont Godinne</name>
      <address>
        <city>Yvoir</city>
        <zip>5530</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Local Investigator: Carlos Graux, MD, PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13824-9. doi: 10.1073/pnas.1008051107. Epub 2010 Jul 14.</citation>
    <PMID>20631300</PMID>
  </reference>
  <reference>
    <citation>Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68. doi: 10.1080/14653240902960411.</citation>
    <PMID>19530029</PMID>
  </reference>
  <reference>
    <citation>Van Driessche A, Gao L, Stauss HJ, Ponsaerts P, Van Bockstaele DR, Berneman ZN, Van Tendeloo VF. Antigen-specific cellular immunotherapy of leukemia. Leukemia. 2005 Nov;19(11):1863-71. doi: 10.1038/sj.leu.2403930.</citation>
    <PMID>16121214</PMID>
  </reference>
  <reference>
    <citation>Van Driessche A, Berneman ZN, Van Tendeloo VF. Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials. Oncologist. 2012;17(2):250-9. doi: 10.1634/theoncologist.2011-0240. Epub 2012 Jan 30.</citation>
    <PMID>22291091</PMID>
  </reference>
  <reference>
    <citation>Anguille S, Willemen Y, Lion E, Smits EL, Berneman ZN. Dendritic cell vaccination in acute myeloid leukemia. Cytotherapy. 2012 Jul;14(6):647-56. doi: 10.3109/14653249.2012.693744.</citation>
    <PMID>22686130</PMID>
  </reference>
  <reference>
    <citation>Anguille S, Lion E, Smits E, Berneman ZN, van Tendeloo VF. Dendritic cell vaccine therapy for acute myeloid leukemia: questions and answers. Hum Vaccin. 2011 May;7(5):579-84. doi: 10.4161/hv.7.5.14652. Epub 2011 May 1.</citation>
    <PMID>21422813</PMID>
  </reference>
  <reference>
    <citation>Smits EL, Anguille S, Cools N, Berneman ZN, Van Tendeloo VF. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009 Oct;20(10):1106-18. doi: 10.1089/hum.2009.145.</citation>
    <PMID>19656053</PMID>
  </reference>
  <reference>
    <citation>Anguille S, Van de Velde AL, Smits EL, Van Tendeloo VF, Juliusson G, Cools N, Nijs G, Stein B, Lion E, Van Driessche A, Vandenbosch I, Verlinden A, Gadisseur AP, Schroyens WA, Muylle L, Vermeulen K, Maes MB, Deiteren K, Malfait R, Gostick E, Lammens M, Couttenye MM, Jorens P, Goossens H, Price DA, Ladell K, Oka Y, Fujiki F, Oji Y, Sugiyama H, Berneman ZN. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood. 2017 Oct 12;130(15):1713-1721. doi: 10.1182/blood-2017-04-780155. Epub 2017 Aug 22.</citation>
    <PMID>28830889</PMID>
  </reference>
  <reference>
    <citation>Van Acker HH, Versteven M, Lichtenegger FS, Roex G, Campillo-Davo D, Lion E, Subklewe M, Van Tendeloo VF, Berneman ZN, Anguille S. Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia. J Clin Med. 2019 Apr 27;8(5):579. doi: 10.3390/jcm8050579.</citation>
    <PMID>31035598</PMID>
  </reference>
  <reference>
    <citation>Smits EL, Stein B, Nijs G, Lion E, Van Tendeloo VF, Willemen Y, Anguille S, Berneman ZN. Generation and Cryopreservation of Clinical Grade Wilms' Tumor 1 mRNA-Loaded Dendritic Cell Vaccines for Cancer Immunotherapy. Methods Mol Biol. 2016;1393:27-35. doi: 10.1007/978-1-4939-3338-9_3.</citation>
    <PMID>27033213</PMID>
  </reference>
  <reference>
    <citation>Z. Berneman, S. Anguille, Y. Willemen, A. Van de Velde, P. Germonpré, M. Huizing, V. Van Tendeloo, K. Saevels, L. Rutsaert, K. Vermeulen, A. Snoeckx, B. Op de Beeck, N. Cools, G. Nijs, B. Stein, E. Lion, A. van Driessche, M. Peeters, E. Smits. Vaccination of cancer patients with dendritic cells electroporated with mRNA encoding the Wilms' Tumor protein (WT1): correlation of clinical effect and overall survival with T-cell response. Cytotherapy 2019, 21(5), p. S10.</citation>
  </reference>
  <reference>
    <citation>Z. Berneman, A. Van de Velde, S. Anguille, Y. Willemen, M. Huizing, P. Germonpré, K. Saevels, G. Nijs, N. Cools, A. Van Driessche, B. Stein, H. De Reu, W. Schroyens, A. Gadisseur, A. Verlinden, K. Vermeulen, M. Maes, M. Lammens, H. Goossens, M. Peeters, V. Van Tendeloo, E. Smits. Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma. Cytotherapy 2016, 18(6), p. S13-14</citation>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>January 15, 2021</last_update_submitted>
  <last_update_submitted_qc>January 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Antwerp</investigator_affiliation>
    <investigator_full_name>Zwi Berneman</investigator_full_name>
    <investigator_title>Full Professor</investigator_title>
  </responsible_party>
  <keyword>in complete remission</keyword>
  <keyword>Adult (&gt;18 years) at very high risk of relapse</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>
  <!-- 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/NCT01686334
org study id: CCRG12-001
nct id: NCT01686334
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
The primary aim of this innovative immunotherapeutic study is to determine whether the
      antileukemic effects seen in our previous phase I/II study can be confirmed in a large cohort
      of patients and whether dendritic cell vaccination can significantly prevent relapse and
      increase survival of acute myeloid leukemia (AML) patients by eradicating minimal residual
      disease.
Together with the Transplant Committee of the Belgian Hematological Society (BHS), we will
      perform a multicenter randomized open-label phase II clinical study in 130 patients with
      acute myeloid leukemia (AML). Adult patients (> 18 years) with AML who have entered
      morphological CR or CRi after (1) intensive chemotherapy (i.e (i) at least one cycle of
      induction and one cycle of consolidation chemotherapy or (ii) one to two cycles of CPX-351
      induction treatment and up to two cycles of CPX-351 consolidation treatment) or (2)
      low-intensity chemotherapy (i.e (iii) at least two cycles to maximum six cycles of
      hypomethylating agents whether or not combined with venetoclax or (iv) at least two cycles to
      maximum six cycles of low-dose cytarabine combined with venetoclax); and fulfilling all other
      eligibility criteria will be randomized to be vaccinated with dendritic cells or to receive
      regular follow-up care. After randomization, patients receiving low-intensity chemotherapy
      are allowed to continue this treatment in combination with DC vaccination or the follow-up
      care. The primary aim of this innovative immunotherapeutic study is to determine whether the
      antileukemic effects seen in our previous phase I/II study can be confirmed in a large cohort
      of patients and whether dendritic cell vaccination can significantly prevent relapse and
      increase survival of AML patients by eradicating minimal residual disease. Patients will be
      recruited at 8 different centers in Belgium. Recruitment will start in the second half of
      2013 and will last for 10 years or until 130 efficacy-evaluable AML patients are included. In
      the interventional group, 65 patients will be treated during two years with autologous
      dendritic cells loaded by messenger RNA electroporation with the Wilms' tumor antigen (WT1).
      The dendritic cell therapy product will be generated and generally administered in the
      coordinating center, which is the Antwerp University Hospital, more specifically the Center
      for Cell Therapy and Regenerative Medicine (CCRG) and the Division of Hematology, both headed
      by Prof. Zwi Berneman. After inclusion of 130 efficacy-evaluable patients, relapse rate,
      relapse-free survival and overall survival analysis will be performed. Tumor marker levels
      and immune activation will also be monitored to compare the 2 groups at a molecular and
      immunological level. General and disease-specific quality of life will be evaluated using
      quality of life questionnaires at regular time points.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: At study completion, an average of 5 year
description: The primary objective of this randomized phase II clinical study is to determine the effect of WT1-targeted dendritic cell vaccination on overall survival in adult AML patients at very high risk of relapse and in complete remission.
measure: Relapse rate
time frame: At study completion, an average of 5 year
description: to determine the effect of WT1-targeted dendritic cell vaccination on relapse rate in adult AML patients at very high risk of relapse and in complete remission.
measure: relapse-free survival
time frame: At study completion, an average of 5 year
description: to determine the effect of WT1-targeted dendritic cell vaccination on relapse-free survival in adult AML patients at very high risk of relapse and in complete remission.
measure: Change in WT1 mRNA levels in peripheral blood
time frame: Through study completion, at every vaccination during 2 years
description: Efficacy assessment will also be performed on a molecular level. To this end, peripheral blood samples will be obtained from participants in both study groups (vaccine group and control group) and analyzed by qRT-PCR for WT1 expression, which is a promising molecular biomarker in AML.
measure: Immune activation
time frame: After the 4th DC vaccine
description: This study aims to examine the presence of leukemia-specific immune responses in AML patients in remission and to investigate whether they can be induced or increased in these patients by WT1 mRNA-electroporated DC vaccination.
measure: General and disease-specific quality of life
time frame: At study completion, an average of 5 year
description: Patients will be asked to fill out general and disease-specific quality of life questionnaires to assess changes in general and disease-specific quality of life during the study at regular time points
measure: Tertiary: Safety
time frame: At study completion, an average of 5 year
description: To corroborate the safety of WT1 mRNA-electroporated DC vaccination in adult patients with AML. Safety will be assessed at every visit by adverse event reporting and clinical laboratory tests.
measure: Exploratory: Effect of low-intensity chemotherapy
time frame: At study completion, an average of 5 year
description: To evaluate the effect of low-intensity chemotherapy on the primary and secondary objectives.
arm group label: DC vaccine
arm group type: Experimental
description: Vaccination with autologous WT1 mRNA-electroporated DCs plus follow-up care. Patients receiving low-intensity chemotherapy are allowed to continue this treatment in combination with DC vaccination.
arm group label: Control arm
arm group type: No Intervention
description: Follow-up care. Patients receiving low-intensity chemotherapy are allowed to continue this treatment during the follow-up care
intervention type: Biological
intervention name: DC vaccine
description: Autologous WT1 mRNA-electroporated DCs
arm group label: DC vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Zwi Berneman, MD, PhD
role: Study Director
affiliation: University Hospital, Antwerp
last name: Evelien LJ Smits, MSc, PhD
role: Principal Investigator
affiliation: Universiteit Antwerpen
last name: Sébastien Anguille, MD, PhD
role: Principal Investigator
affiliation: University Hospital, Antwerp
last name: Ann Van de Velde, MD, PhD
role: Principal Investigator
affiliation: University Hospital, Antwerp
last name: Zwi N Berneman, MD, PhD
phone: +32 3 8213780
email: zwi.berneman@uza.be
last name: Ann Van de Velde, MD, PhD
phone: +32 3 8213916
email: ann.vandevelde@uza.be
facility: 
status: Recruiting
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status: Recruiting
investigator: 
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status: Recruiting
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country: Belgium
citation: Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13824-9. doi: 10.1073/pnas.1008051107. Epub 2010 Jul 14.
PMID: 20631300
citation: Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68. doi: 10.1080/14653240902960411.
PMID: 19530029
citation: Van Driessche A, Gao L, Stauss HJ, Ponsaerts P, Van Bockstaele DR, Berneman ZN, Van Tendeloo VF. Antigen-specific cellular immunotherapy of leukemia. Leukemia. 2005 Nov;19(11):1863-71. doi: 10.1038/sj.leu.2403930.
PMID: 16121214
citation: Van Driessche A, Berneman ZN, Van Tendeloo VF. Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials. Oncologist. 2012;17(2):250-9. doi: 10.1634/theoncologist.2011-0240. Epub 2012 Jan 30.
PMID: 22291091
citation: Anguille S, Willemen Y, Lion E, Smits EL, Berneman ZN. Dendritic cell vaccination in acute myeloid leukemia. Cytotherapy. 2012 Jul;14(6):647-56. doi: 10.3109/14653249.2012.693744.
PMID: 22686130
citation: Anguille S, Lion E, Smits E, Berneman ZN, van Tendeloo VF. Dendritic cell vaccine therapy for acute myeloid leukemia: questions and answers. Hum Vaccin. 2011 May;7(5):579-84. doi: 10.4161/hv.7.5.14652. Epub 2011 May 1.
PMID: 21422813
citation: Smits EL, Anguille S, Cools N, Berneman ZN, Van Tendeloo VF. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009 Oct;20(10):1106-18. doi: 10.1089/hum.2009.145.
PMID: 19656053
citation: Anguille S, Van de Velde AL, Smits EL, Van Tendeloo VF, Juliusson G, Cools N, Nijs G, Stein B, Lion E, Van Driessche A, Vandenbosch I, Verlinden A, Gadisseur AP, Schroyens WA, Muylle L, Vermeulen K, Maes MB, Deiteren K, Malfait R, Gostick E, Lammens M, Couttenye MM, Jorens P, Goossens H, Price DA, Ladell K, Oka Y, Fujiki F, Oji Y, Sugiyama H, Berneman ZN. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood. 2017 Oct 12;130(15):1713-1721. doi: 10.1182/blood-2017-04-780155. Epub 2017 Aug 22.
PMID: 28830889
citation: Van Acker HH, Versteven M, Lichtenegger FS, Roex G, Campillo-Davo D, Lion E, Subklewe M, Van Tendeloo VF, Berneman ZN, Anguille S. Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia. J Clin Med. 2019 Apr 27;8(5):579. doi: 10.3390/jcm8050579.
PMID: 31035598
citation: Smits EL, Stein B, Nijs G, Lion E, Van Tendeloo VF, Willemen Y, Anguille S, Berneman ZN. Generation and Cryopreservation of Clinical Grade Wilms' Tumor 1 mRNA-Loaded Dendritic Cell Vaccines for Cancer Immunotherapy. Methods Mol Biol. 2016;1393:27-35. doi: 10.1007/978-1-4939-3338-9_3.
PMID: 27033213
citation: Z. Berneman, S. Anguille, Y. Willemen, A. Van de Velde, P. Germonpré, M. Huizing, V. Van Tendeloo, K. Saevels, L. Rutsaert, K. Vermeulen, A. Snoeckx, B. Op de Beeck, N. Cools, G. Nijs, B. Stein, E. Lion, A. van Driessche, M. Peeters, E. Smits. Vaccination of cancer patients with dendritic cells electroporated with mRNA encoding the Wilms' Tumor protein (WT1): correlation of clinical effect and overall survival with T-cell response. Cytotherapy 2019, 21(5), p. S10.
citation: Z. Berneman, A. Van de Velde, S. Anguille, Y. Willemen, M. Huizing, P. Germonpré, K. Saevels, G. Nijs, N. Cools, A. Van Driessche, B. Stein, H. De Reu, W. Schroyens, A. Gadisseur, A. Verlinden, K. Vermeulen, M. Maes, M. Lammens, H. Goossens, M. Peeters, V. Van Tendeloo, E. Smits. Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma. Cytotherapy 2016, 18(6), p. S13-14
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Antwerp
investigator full name: Zwi Berneman
investigator title: Full Professor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute