<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/NCT03249870</url>
  </required_header>
  <id_info>
    <org_study_id>P16/11- EWALL INO</org_study_id>
    <secondary_id>2016-004942-27</secondary_id>
    <nct_id>NCT03249870</nct_id>
  </id_info>
  <brief_title>Study of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL</brief_title>
  <acronym>EWALL-INO</acronym>
  <official_title>A Phase 2 Study of Inotuzumab Ozogamicin (INO) Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Versailles Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Versailles Hospital</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 aim of the present EWALL-INO study is to confirm very promising results obtained with a&#xD;
      combination of INO and mild chemotherapy in older de novo CD22+ B-ALL patients. For that&#xD;
      purpose, safety and efficacy of a weekly INO administration combined to mild-intensity&#xD;
      chemotherapy will be evaluated in a cohort of patients aged more than 55 years with newly&#xD;
      diagnosed previously untreated Ph-negative (CD22+) BCP-ALL. Conversely to the MDACC&#xD;
      miniHCVD-INO study and in order to lower the overall toxicity of the combination, INO will be&#xD;
      given as part of the remission induction treatment phase during the first 2 treatment cycles&#xD;
      only, in combination with corticosteroid, vincristine, cyclophosphamide and intrathecal&#xD;
      prophylaxis only; then, all responding patients will received standard INO-free chemotherapy&#xD;
      as consolidation and maintenance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INO schedule of administration will be as described in the refractory/relapsed INO-VATE study&#xD;
      for the first cycle, with sequential day 1/8/15 doses of 0.8, 0.5 and 0.5 mg/m2,&#xD;
      respectively. Reduced dose of INO will be used for the second and last cycle (0.5 mg/m2 on&#xD;
      day 1/8). This was retained in order:&#xD;
&#xD;
        1. to minimize potential toxicities, including liver disorders and prolonged&#xD;
           thrombocytopenia; and&#xD;
&#xD;
        2. to allow delivery of subsequent chemotherapy consolidations cycles.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 28, 2017</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Actual">May 30, 2023</primary_completion_date>
  <phase>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>Assessment of overall survival (OS)</measure>
    <time_frame>one year</time_frame>
    <description>The primary objective of the trial is to assess overall survival (OS) observed at 1 year after administration of INO and chemotherapy in older Ph-negative BCP-ALL patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of adverse events (AEs)</measure>
    <time_frame>3 months</time_frame>
    <description>Type, duration and frequency of AEs up to 3 months of induction course 1 or 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of complete remission (CR / CRp)</measure>
    <time_frame>35 days</time_frame>
    <description>CR/CRp response rate after INO-based induction course 1 and 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Minimal residual disease (MRD)</measure>
    <time_frame>35 days</time_frame>
    <description>Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of early death</measure>
    <time_frame>100 days</time_frame>
    <description>Early death (ED) rate at 30, 60 and 100 day from treatment initiation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)</measure>
    <time_frame>one year</time_frame>
    <description>Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">130</enrollment>
  <condition>Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)</condition>
  <arm_group>
    <arm_group_label>Inotuzumab ozogamicin (INO)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inotuzumab ozogamicin (INO)</intervention_name>
    <description>INO schedule of administration is as follows:&#xD;
First induction course: 0.8 mg/m² on day 1, 0.5 mg/m² on day 8, and 0.5 mg/m² on day 15&#xD;
Second induction course: 0.5 mg/m² on day 1, and 0.5 mg/m² on day 8</description>
    <arm_group_label>Inotuzumab ozogamicin (INO)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged more than 55 years old,&#xD;
&#xD;
          -  With confirmed diagnosis of BCP-ALL according to World Health Organisation (WHO)&#xD;
             criteria expressing the CD22 antigen by flow cytometry (20% or more positive blast&#xD;
             cells),&#xD;
&#xD;
          -  Without central nervous system (CNS) involvement,&#xD;
&#xD;
          -  Without BCR-ABL fusion by standard cytogenetics, Fluorescence In Situ Hybridization&#xD;
             (FISH) analysis and/or RT-PCR,&#xD;
&#xD;
          -  Previously untreated,&#xD;
&#xD;
          -  Eligible to intensive chemotherapy, due to general health status,&#xD;
&#xD;
          -  ECOG performance status ≤ 2,&#xD;
&#xD;
          -  Patients must have the following laboratory values unless considered due to leukemia:&#xD;
             AST and ALT ≤ 2.5 x upper the limit of normal (ULN); estimated GFR ≥ 50 mL/min using&#xD;
             the MDRD equation; total and direct serum bilirubin ≤ 1.5 x ULN; electrolyte panel&#xD;
             within normal ranges for the institution unless attributed to the underlying disease.&#xD;
&#xD;
          -  Written informed consent obtained prior to any screening procedures.&#xD;
&#xD;
          -  Eligible for National Health Insurance in France.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent therapy with any other investigational agent or cytotoxic drug,&#xD;
&#xD;
          -  Prior documented chronic liver disease,&#xD;
&#xD;
          -  Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) or positive HIV serology,&#xD;
&#xD;
          -  Female patients who are pregnant or breast feeding or patients of childbearing&#xD;
             potential not willing to use a double barrier method of contraception during the study&#xD;
             and for 3 months following the last dose of maintenance.&#xD;
&#xD;
          -  Male patients whose sexual partner(s) are women of childbearing potential who are not&#xD;
             willing to use a double barrier method of contraception, one of which includes a&#xD;
             condom, during the study and for 3 months following the last dose of maintenance.&#xD;
&#xD;
          -  Any of concurrent severe and/or uncontrolled medical condition, which could compromise&#xD;
             participation in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrice CHEVALLIER, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nantes University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CH Amiens sud</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Angers</name>
      <address>
        <city>Angers</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Victor Dupouy</name>
      <address>
        <city>Argenteuil</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH cote basque</name>
      <address>
        <city>Bayonne</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Besançon</name>
      <address>
        <city>Besançon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Avicenne</name>
      <address>
        <city>Bobigny</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Duchenne</name>
      <address>
        <city>Boulogne-sur-Mer</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Caen</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Rene Dubois</name>
      <address>
        <city>Cergy-Pontoise</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH metropole Savoie_ chambery</name>
      <address>
        <city>Chambéry</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HIA Percy</name>
      <address>
        <city>Clamart</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Clermond Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Mondor</name>
      <address>
        <city>Créteil</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Dijon</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Grenoble</name>
      <address>
        <city>Grenoble</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU la Reunion</name>
      <address>
        <city>La Réunion</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Versailles</name>
      <address>
        <city>Le Chesnay</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Limoges</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IPC</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Meaux</name>
      <address>
        <city>Meaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Montpellier</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Lacassagne</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nice</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nimes</name>
      <address>
        <city>Nîmes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR Orléans</name>
      <address>
        <city>Orléans</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Necker</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital St Antoine</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital St Louis</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Haut Leveque</name>
      <address>
        <city>Pessac</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Reims</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Roubaix</name>
      <address>
        <city>Roubaix</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre H Becquerel Rouen</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de cancerologie</name>
      <address>
        <city>Saint-Priest-en-Jarez</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IUCT Oncopole</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Valenciennes</name>
      <address>
        <city>Valenciennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Nancy</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>September 4, 2023</last_update_submitted>
  <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nantes University Hospital</investigator_affiliation>
    <investigator_full_name>Patrice Chevallier</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Philadelphia Chromosome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inotuzumab Ozogamicin</mesh_term>
  </intervention_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/NCT03249870
org study id: P16/11- EWALL INO
secondary id: 2016-004942-27
nct id: NCT03249870
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of the present EWALL-INO study is to confirm very promising results obtained with a
      combination of INO and mild chemotherapy in older de novo CD22+ B-ALL patients. For that
      purpose, safety and efficacy of a weekly INO administration combined to mild-intensity
      chemotherapy will be evaluated in a cohort of patients aged more than 55 years with newly
      diagnosed previously untreated Ph-negative (CD22+) BCP-ALL. Conversely to the MDACC
      miniHCVD-INO study and in order to lower the overall toxicity of the combination, INO will be
      given as part of the remission induction treatment phase during the first 2 treatment cycles
      only, in combination with corticosteroid, vincristine, cyclophosphamide and intrathecal
      prophylaxis only; then, all responding patients will received standard INO-free chemotherapy
      as consolidation and maintenance.
INO schedule of administration will be as described in the refractory/relapsed INO-VATE study
      for the first cycle, with sequential day 1/8/15 doses of 0.8, 0.5 and 0.5 mg/m2,
      respectively. Reduced dose of INO will be used for the second and last cycle (0.5 mg/m2 on
      day 1/8). This was retained in order:

        1. to minimize potential toxicities, including liver disorders and prolonged
           thrombocytopenia; and

        2. to allow delivery of subsequent chemotherapy consolidations cycles.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assessment of overall survival (OS)
time frame: one year
description: The primary objective of the trial is to assess overall survival (OS) observed at 1 year after administration of INO and chemotherapy in older Ph-negative BCP-ALL patients.
measure: Assessment of adverse events (AEs)
time frame: 3 months
description: Type, duration and frequency of AEs up to 3 months of induction course 1 or 2
measure: Rate of complete remission (CR / CRp)
time frame: 35 days
description: CR/CRp response rate after INO-based induction course 1 and 2
measure: Assessment of Minimal residual disease (MRD)
time frame: 35 days
description: Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes
measure: Rate of early death
time frame: 100 days
description: Early death (ED) rate at 30, 60 and 100 day from treatment initiation
measure: Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
time frame: one year
description: Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
arm group label: Inotuzumab ozogamicin (INO)
arm group type: Experimental
intervention type: Drug
intervention name: Inotuzumab ozogamicin (INO)
description: INO schedule of administration is as follows:
First induction course: 0.8 mg/m² on day 1, 0.5 mg/m² on day 8, and 0.5 mg/m² on day 15
Second induction course: 0.5 mg/m² on day 1, and 0.5 mg/m² on day 8
arm group label: Inotuzumab ozogamicin (INO)
criteria: 
gender: All
minimum age: 55 Years
maximum age: N/A
healthy volunteers: No
last name: Patrice CHEVALLIER, MD
role: Principal Investigator
affiliation: Nantes University Hospital
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country: France
responsible party type: Principal Investigator
investigator affiliation: Nantes University Hospital
investigator full name: Patrice Chevallier
investigator title: MD, PhD
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Philadelphia Chromosome
mesh term: Inotuzumab Ozogamicin
sharing ipd: No