<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/NCT03275636</url>
  </required_header>
  <id_info>
    <org_study_id>DKMS-16-01</org_study_id>
    <secondary_id>2015-005399-12</secondary_id>
    <nct_id>NCT03275636</nct_id>
  </id_info>
  <brief_title>Haploidentical Donor vs mMUD in Hematological Malignancies</brief_title>
  <acronym>HAMLET</acronym>
  <official_title>A Randomized Controlled Trial Comparing Outcome After Hematopoietic Cell Transplantation From a Partially Matched Unrelated Versus Haploidentical Donor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>DKMS gemeinnützige GmbH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>DKMS gemeinnützige GmbH</source>
  <oversight_info>
    <has_dmc>Yes</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 goal of this trial is to compare the outcome after partially matched (single mismatch)&#xD;
      unrelated donor transplantation with haploidentical transplantation in a randomized&#xD;
      controlled setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For patients with an indication for allogeneic HCT, the search for a stem cell donor is a&#xD;
      challenge. 20% of patients who need an allograft have an HLA-identical sibling available, and&#xD;
      for approximately 70% of the remaining patients, a suitable, HLA-well-matched (10/10),&#xD;
      unrelated volunteer can be found. For the remaining patients, partially matched (single&#xD;
      mismatch) unrelated donors or haploidentical donors are alternative options.&#xD;
&#xD;
      Recently published retrospective single center and registry studies suggest comparable&#xD;
      outcomes for HCT from unrelated donors matched at HLA -A, -B, -C, and -DRB1 and&#xD;
      haploidentical donors. The number of haploidentical HCT evaluated in these studies was still&#xD;
      relatively small and a selection bias for the retrospective comparisons cannot be excluded.&#xD;
&#xD;
      The goal of this trial is to evaluate overall survival of patients with high-risk AML, ALL or&#xD;
      MDS after partially matched unrelated or haploidentical donor transplantation..&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Anticipated">April 2024</completion_date>
  <primary_completion_date type="Anticipated">April 2024</primary_completion_date>
  <phase>Phase 2/Phase 3</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>2 years</time_frame>
    <description>Overall survival calculated from the time of randomization will be the primary endpoint of this trial. Death from any reason will be considered as event.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Engraftment rate</measure>
    <time_frame>day 56</time_frame>
    <description>Engraftment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune-reconstitution rate</measure>
    <time_frame>day56</time_frame>
    <description>Immune-reconstitution rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infections</measure>
    <time_frame>2 months after HCT</time_frame>
    <description>Severe infections rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event Free Survival</measure>
    <time_frame>1 year</time_frame>
    <description>Event Free Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft vs Host Disease</measure>
    <time_frame>1 year</time_frame>
    <description>Graft vs Host Disease rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft vs Host Disease-free survival</measure>
    <time_frame>1 year</time_frame>
    <description>Graft vs Host Disease-free survival rate</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">98</enrollment>
  <condition>AML</condition>
  <condition>ALL</condition>
  <condition>MDS</condition>
  <arm_group>
    <arm_group_label>Haploidentical donor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Peripheral blood stem cells from Haploidentical donor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>partially matched unrelated donor</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Peripheral blood stem cells from unrelated donor with a single allele or antigen mismatch at HLA-A, -B, -C, or -DRB1 and no concurrent DQB1 mismatch (9/10) shown by confirmatory typing</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Peripheral blood stem cells</intervention_name>
    <description>Hematopoietic stem cell transplantation with PBSC</description>
    <arm_group_label>Haploidentical donor</arm_group_label>
    <arm_group_label>partially matched unrelated donor</arm_group_label>
    <other_name>PBSC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Eligible diagnoses are listed below:&#xD;
&#xD;
             AML with adverse risk genetic abnormalities (according to the ELN guidelines)1. AML&#xD;
             with intermediate genetic abnormalities (according to ELN guidelines) either in first&#xD;
             complete remission, after relapse, or by chemotherapy-refractory disease.&#xD;
&#xD;
             AML with favourable genetic abnormalities (according to ELN guidelines) after relapse&#xD;
             or by chemotherapy-refractory disease, except APL.&#xD;
&#xD;
             AML with undefined genetic risk classification after relapse or with&#xD;
             chemotherapy-refractory disease.&#xD;
&#xD;
             AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative neoplasia,&#xD;
             except if favourable genetic abnormalities (according to ELN guidelines) are present.&#xD;
&#xD;
             Therapy-related myeloid neoplasia except if favorable genetic abnormalities (according&#xD;
             to ELN guidelines) are present.&#xD;
&#xD;
             MDS with high risk or very high risk disease (according to the IPSS-R score)2.&#xD;
&#xD;
             First CR of high-risk ALL, defined by one or more of these:&#xD;
&#xD;
               -  Early or mature T-ALL (CD1a negative).&#xD;
&#xD;
               -  Pro B-ALL with t(4v;11); KMT2A-rearrangements.&#xD;
&#xD;
               -  Presence of BCR-ABL and/or t(9;22).&#xD;
&#xD;
               -  Persistence of minimal residual disease after the second induction course. ALL&#xD;
                  with or without complete remission after salvage therapy following poor response&#xD;
                  to induction therapy.&#xD;
&#xD;
             ALL after haematological or molecular relapse.&#xD;
&#xD;
          2. Fit for transplant according to physician judgement.&#xD;
&#xD;
          3. No history of cardiac disease and absence of active symptoms, otherwise, documented&#xD;
             left ventricular ejection fraction ≥40%.&#xD;
&#xD;
          4. No history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented&#xD;
             diffusion lung capacity for carbon monoxide (DLCO) ≥40% or FEV1/FVC ≥ 50% despite&#xD;
             appropriate treatment&#xD;
&#xD;
          5. Availability of ≥1 unrelated donor with a single allele or antigen mismatch at HLA-A,&#xD;
             -B, -C, or -DRB1 and no concurrent DQB1 mismatch (9/10) shown by confirmatory typing.&#xD;
&#xD;
          6. Availability of at least one haploidentical donor meeting the following criteria:&#xD;
&#xD;
        Donor is a biologic parent / child of the patient, or haploidentity has been confirmed for&#xD;
        patient's relatives by HLA-Typing.&#xD;
&#xD;
        The donor has expressed his/her will to donate and has no contraindications against a stem&#xD;
        cell donation by medical history.&#xD;
&#xD;
        Donor age is ≥18 years and ≤75 years.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Relapse or graft failure after a first allogeneic transplantation.&#xD;
&#xD;
          2. Thymic ALL in first complete remission.&#xD;
&#xD;
          3. Severe organ dysfunction defined by either of the following three criteria:&#xD;
&#xD;
             Patients who receive supplementary continuous oxygen. Serum bilirubin &gt;1.5 x ULN (if&#xD;
             not considered Gilbert-Syndrome) or ASAT/ALAT &gt;5 x ULN.&#xD;
&#xD;
             Estimated Glomerular Filtration Rate (GFR) &lt; 40 mL/min&#xD;
&#xD;
          4. Uncontrolled infection at the time of enrollment.&#xD;
&#xD;
          5. Pregnant or breast-feeding women.&#xD;
&#xD;
          6. An HLA-identical sibling donor or 8/8 (HLA-A, -B, -C, or -DRB1) matched unrelated&#xD;
             donor is available and suitable to donate prior to randomization.&#xD;
&#xD;
          7. Men unable or unwilling to use adequate contraception methods from enrollment to&#xD;
             minimum of six months after the last dose of chemotherapy.&#xD;
&#xD;
          8. Women of childbearing potential except those who fulfill the following criteria:&#xD;
             Post-menopausal or post-operative or continuous and correct application of a&#xD;
             contraception method with a Pearl Index &lt;1% or sexual abstinence or vasectomy of the&#xD;
             sexual partner.&#xD;
&#xD;
          9. Simultaneous participation in another clinical trial.&#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>Johannes Schetelig, Prof Dr med</last_name>
    <role>Study Chair</role>
    <affiliation>Universtitätsklinikum Dresden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitätsklinikum Bonn</name>
      <address>
        <city>Bonn</city>
        <zip>53105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Dresden</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Frankfurt</name>
      <address>
        <city>Frankfurt am Main</city>
        <zip>60595</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Halle (Saale)</name>
      <address>
        <city>Halle</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Mannheim</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Münster</name>
      <address>
        <city>Münster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Nürnberg Nord</name>
      <address>
        <city>Nürnberg</city>
        <zip>90419</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert-Bosch-Krankenhaus</name>
      <address>
        <city>Stuttgart</city>
        <zip>70376</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Tübingen</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>July 12, 2023</last_update_submitted>
  <last_update_submitted_qc>July 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Haploidentical</keyword>
  <keyword>mismatched unrelated donor</keyword>
  <keyword>hematopoietic stem cell transplantation</keyword>
  <keyword>donor comparison</keyword>
  <!-- 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/NCT03275636
org study id: DKMS-16-01
secondary id: 2015-005399-12
nct id: NCT03275636
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The goal of this trial is to compare the outcome after partially matched (single mismatch)
      unrelated donor transplantation with haploidentical transplantation in a randomized
      controlled setting.
For patients with an indication for allogeneic HCT, the search for a stem cell donor is a
      challenge. 20% of patients who need an allograft have an HLA-identical sibling available, and
      for approximately 70% of the remaining patients, a suitable, HLA-well-matched (10/10),
      unrelated volunteer can be found. For the remaining patients, partially matched (single
      mismatch) unrelated donors or haploidentical donors are alternative options.

      Recently published retrospective single center and registry studies suggest comparable
      outcomes for HCT from unrelated donors matched at HLA -A, -B, -C, and -DRB1 and
      haploidentical donors. The number of haploidentical HCT evaluated in these studies was still
      relatively small and a selection bias for the retrospective comparisons cannot be excluded.

      The goal of this trial is to evaluate overall survival of patients with high-risk AML, ALL or
      MDS after partially matched unrelated or haploidentical donor transplantation..
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: 2 years
description: Overall survival calculated from the time of randomization will be the primary endpoint of this trial. Death from any reason will be considered as event.
measure: Engraftment rate
time frame: day 56
description: Engraftment
measure: Immune-reconstitution rate
time frame: day56
description: Immune-reconstitution rate
measure: Infections
time frame: 2 months after HCT
description: Severe infections rate
measure: Event Free Survival
time frame: 1 year
description: Event Free Survival
measure: Graft vs Host Disease
time frame: 1 year
description: Graft vs Host Disease rate
measure: Graft vs Host Disease-free survival
time frame: 1 year
description: Graft vs Host Disease-free survival rate
arm group label: Haploidentical donor
arm group type: Experimental
description: Peripheral blood stem cells from Haploidentical donor
arm group label: partially matched unrelated donor
arm group type: Active Comparator
description: Peripheral blood stem cells from unrelated donor with a single allele or antigen mismatch at HLA-A, -B, -C, or -DRB1 and no concurrent DQB1 mismatch (9/10) shown by confirmatory typing
intervention type: Biological
intervention name: Peripheral blood stem cells
description: Hematopoietic stem cell transplantation with PBSC
arm group label: Haploidentical donor
arm group label: partially matched unrelated donor
other name: PBSC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Johannes Schetelig, Prof Dr med
role: Study Chair
affiliation: Universtitätsklinikum Dresden
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor