<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/NCT03250546</url>
  </required_header>
  <id_info>
    <org_study_id>P151001</org_study_id>
    <nct_id>NCT03250546</nct_id>
  </id_info>
  <brief_title>Haploidentical and Mismatched Unrelated Donors Hematopoietic Stem Cell Transplant</brief_title>
  <acronym>ALTERGREF</acronym>
  <official_title>Randomized Prospective Phase II Clinical Trial Using Post-Transplantation Cyclophosphamide for Prevention of GVHD in Haploidentical and HLA-9/10 Mismatched Unrelated Donors Hematopoietic Stem Cell Transplant</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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 primary objective of this study is to compare the 2-year progression free survival&#xD;
      without acute graft versus host disease (GvHD) (aGvHD) grade III-IV or without moderate or&#xD;
      severe chronic (cGVHD) after transplant from haploidentical hematopoietic stell cell&#xD;
      transplant (HSCT) or from an unrelated Human Leukocyte Antigen (HLA)-9/10 mismatched&#xD;
      unrelated donor (MMUD).&#xD;
&#xD;
      It will use a Phase II, multicenter, prospective, randomized clinical trial.&#xD;
&#xD;
      By setting a power of 80% and a type I error rate of 5% for a two-sided log-rank test&#xD;
      (hypotheses tested: probability of event-free survival at 2 years 50% vs. 30 %), 92 patients&#xD;
      need to be recruited in each arm, for a total of 184 patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 20, 2017</start_date>
  <completion_date type="Anticipated">November 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2022</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>
    <intervention_model_description>Randomized prospective Phase II Clinical Trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Two-year progression free survival, without acute GVHD grade III-IV and without moderate/severe cGVHD</measure>
    <time_frame>2 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>100 day engraftment</measure>
    <time_frame>day 100</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Progression Free survival</measure>
    <time_frame>2 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Cumulative incidence of progression</measure>
    <time_frame>2 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Acute GVHD incidence</measure>
    <time_frame>day 100</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Chronic GVHD incidence</measure>
    <time_frame>2 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Non relapse Mortality (NRM)</measure>
    <time_frame>year 2</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Stages of Chimerism</measure>
    <time_frame>month 1, 2, 3, 6 and 12</time_frame>
    <description>Complete chimerism: 100% donor cells detected, suggesting complete hematopoietic replacement&#xD;
Mixed chimerism: Host cells are detected in particular cells like lymphocytes. Five to 90% donor cells&#xD;
Split chimerism: One or more lineages are of host and one or more lineages are of donor, like myeloid cells are 100% host and T-cells are 100% donor.</description>
  </other_outcome>
  <other_outcome>
    <measure>Severe infections</measure>
    <time_frame>2 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time interval between diagnosis and transplant</measure>
    <time_frame>day 100</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Adverse events</measure>
    <time_frame>day 100 and two years</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">184</enrollment>
  <condition>Hematopoietic Stem Cell Transplant</condition>
  <arm_group>
    <arm_group_label>Haplo-identical group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>HLA-9/10 MMUD group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>transplant from a haplo-identical donor</intervention_name>
    <description>The transplant procedures will be similar in the 2 groups beside the origin of cells</description>
    <arm_group_label>Haplo-identical group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>transplant from a non related donor</intervention_name>
    <description>The transplant procedures will be similar in the 2 groups beside the origin of cells</description>
    <arm_group_label>HLA-9/10 MMUD group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  With a hematological malignancy requiring a HSCT and at least in partial response ie&#xD;
             a) Acute Leukemia in complete remission, b) Myelodysplastic syndromes with less than&#xD;
             20% marrow, c) Myeloproliferative syndromes with less than 20% bone marrow blasts, d)&#xD;
             Non Hodgkin Lymphoma (NHL), Hodgkin's disease, chronic lymphocytic leukemia at least&#xD;
             in partial response, e) Myeloma at least in partial response.&#xD;
&#xD;
          -  Without HLA matched related or unrelated donor&#xD;
&#xD;
          -  Identification of a possible HLA-9/10 MMUD and a possible haplo-identical donor.&#xD;
&#xD;
          -  Having read and understood the information letter and signed the informed consent&#xD;
&#xD;
          -  With health insurance coverage&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Organic or psychiatric disease, non related to the hematological malignancy,&#xD;
             contraindicating the transplant.&#xD;
&#xD;
          -  Performance Scale by the Eastern Cooperative Oncology Group (ECOG)&gt; 2&#xD;
&#xD;
          -  Severe uncontrolled infection&#xD;
&#xD;
          -  Cardiac contraindication of post-transplant Cy (coronary insufficiency, ejection&#xD;
             ventricular fraction &lt;50%)&#xD;
&#xD;
          -  Aspartate transaminase (AST) and alanine transaminase (ALT) &gt; 2.5 N, creatinine &gt; 150&#xD;
             mmol/L (except if related to malignancy)&#xD;
&#xD;
          -  Previous active cancer in the last two years, except basal cell skin cancer and in&#xD;
             situ carcinoma of the cervix&#xD;
&#xD;
          -  Childbearing age woman refusing contraception&#xD;
&#xD;
          -  Patients who did not accept the follow-up planned by the protocol&#xD;
&#xD;
          -  Positive serology for HIV or Human T-Lymphotropic Virus (HTLV)-1, 2, or active viral&#xD;
             infection by the Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV)&#xD;
&#xD;
          -  Pregnant woman (positive β-HCG) or during lactation&#xD;
&#xD;
          -  Adult patient on guardianship, or safeguard justice&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Saint Louis hospital</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathalie DHEDIN, MD</last_name>
      <phone>33+142385127</phone>
      <email>nathalie.dhedin@aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Nathalie Dhedin, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service Hématologie Clinique</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stéphanie NGUYEN, MD PhD</last_name>
      <phone>33+142162823</phone>
      <email>stephanie.nguyen-quoc@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>February 18, 2019</last_update_submitted>
  <last_update_submitted_qc>February 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT03250546
org study id: P151001
nct id: NCT03250546
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to compare the 2-year progression free survival
      without acute graft versus host disease (GvHD) (aGvHD) grade III-IV or without moderate or
      severe chronic (cGVHD) after transplant from haploidentical hematopoietic stell cell
      transplant (HSCT) or from an unrelated Human Leukocyte Antigen (HLA)-9/10 mismatched
      unrelated donor (MMUD).

      It will use a Phase II, multicenter, prospective, randomized clinical trial.

      By setting a power of 80% and a type I error rate of 5% for a two-sided log-rank test
      (hypotheses tested: probability of event-free survival at 2 years 50% vs. 30 %), 92 patients
      need to be recruited in each arm, for a total of 184 patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized prospective Phase II Clinical Trial
primary purpose: Treatment
masking: None (Open Label)
measure: Two-year progression free survival, without acute GVHD grade III-IV and without moderate/severe cGVHD
time frame: 2 year
measure: 100 day engraftment
time frame: day 100
measure: Overall survival
time frame: 2 year
measure: Progression Free survival
time frame: 2 year
measure: Cumulative incidence of progression
time frame: 2 year
measure: Acute GVHD incidence
time frame: day 100
measure: Chronic GVHD incidence
time frame: 2 year
measure: Non relapse Mortality (NRM)
time frame: year 2
measure: Stages of Chimerism
time frame: month 1, 2, 3, 6 and 12
description: Complete chimerism: 100% donor cells detected, suggesting complete hematopoietic replacement
Mixed chimerism: Host cells are detected in particular cells like lymphocytes. Five to 90% donor cells
Split chimerism: One or more lineages are of host and one or more lineages are of donor, like myeloid cells are 100% host and T-cells are 100% donor.
measure: Severe infections
time frame: 2 year
measure: Time interval between diagnosis and transplant
time frame: day 100
measure: Adverse events
time frame: day 100 and two years
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
arm group label: Haplo-identical group
arm group type: Experimental
arm group label: HLA-9/10 MMUD group
arm group type: Active Comparator
intervention type: Procedure
intervention name: transplant from a haplo-identical donor
description: The transplant procedures will be similar in the 2 groups beside the origin of cells
arm group label: Haplo-identical group
intervention type: Procedure
intervention name: transplant from a non related donor
description: The transplant procedures will be similar in the 2 groups beside the origin of cells
arm group label: HLA-9/10 MMUD group
criteria: 
gender: All
minimum age: 15 Years
maximum age: 55 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor