<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/NCT03751072</url>
  </required_header>
  <id_info>
    <org_study_id>FRENCH-CYTO</org_study_id>
    <nct_id>NCT03751072</nct_id>
  </id_info>
  <brief_title>Efficacy and Toxicity of Blinatumomab in the French ATU for Adult BCP-ALL R/R, or With MRD+ (FRENCH-CYTO)</brief_title>
  <acronym>FRENCH-CYTO</acronym>
  <official_title>Efficacy and Toxicity of Blinatumomab in the French Compassionate Use Program (ATU) for Adult Patients With B-cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Refractory, in Relapse, or With Positive Minimal Residual Disease.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Group for Research in Adult Acute Lymphoblastic Leukemia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Group for Research in Adult Acute Lymphoblastic Leukemia</source>
  <brief_summary>
    <textblock>
      The outcome of young adults (18-60 years) with ALL has been dramatically improved by the use&#xD;
      of pediatric-inspired trials. About 60% of these young adult patients will be cured at 5&#xD;
      years. In this context, early evaluation of minimal residual disease (MRD) at complete&#xD;
      remission has been shown to be one of the most powerful prognostic factor, but also&#xD;
      predictive of the benefit of allogeneic stem cell transplantation (ASCT). Despite this global&#xD;
      improvement, about 30% of patients experience a relapse and will be exposed to be refractory&#xD;
      to salvage therapy or to early disease escape. In adult ALL, the most important prognostic&#xD;
      factors at relapse are : the time from first CR to relapse, the achievement of a second&#xD;
      complete remission (CR), and the feasibility of ASCT.&#xD;
&#xD;
      Blinatumomab is a bispecific T-cell engager that recruits T-cell on CD19 positive blast cells&#xD;
      and induces anti-leukemic cytotoxicity. In a phase 3 trial in relapse/refractory&#xD;
      Philadelphia-negative (Ph-) ALL, 43% of patients achieved a CR or CR with partial&#xD;
      hematological recovery (CRh), with the majority of responses occurring within the first&#xD;
      cycle. In patients with positive MRD (MRD+) BCP-ALL, blinatumomab resulted in complete MRD&#xD;
      response in 78% of patients after one cycle.&#xD;
&#xD;
      Between 2012 and 2016, blinatumomab was available in France for R/R and MRD+ ALL adult&#xD;
      patients through the French Compassionate Use Program. About 92 adult ALL were treated at&#xD;
      different stages of the disease in 27 centers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To evaluate the efficacy of blinatumomab given in the French Compassionate Use Program, in&#xD;
      term of overall survival in both R/R (first cohort) and MRD positive (second cohort)&#xD;
      patients.&#xD;
&#xD;
      To evaluate the efficacy of blinatumomab given in the French Compassionate Use Program, in&#xD;
      term of CR/CRH in R/R patients, To evaluate the efficacy in term of molecular response in&#xD;
      both R/R and MRD+ cohorts, To evaluate the efficacy of blinatumomab given in the French&#xD;
      Compassionate Use Program, in both Ph+/Ph- ALL patients To evaluate the feasibility and the&#xD;
      safety of blinatumomab administration in a multi-center setting.To evaluate the feasibility&#xD;
      of allogeneic stem cell transplant after blinatumomab administration in both populations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 16, 2018</start_date>
  <completion_date type="Anticipated">January 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival in R/R and MRD+ cohorts</measure>
    <time_frame>6 months</time_frame>
    <description>Months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rates</measure>
    <time_frame>6 months</time_frame>
    <description>Percent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>6 months</time_frame>
    <description>Percent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease free survival</measure>
    <time_frame>6 months</time_frame>
    <description>Months</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">92</enrollment>
  <condition>Acute Lymphoblastic Leukemia, in Relapse</condition>
  <condition>Acute Lymphoblastic Leukemia With Failed Remission</condition>
  <arm_group>
    <arm_group_label>Relapse/Refractory</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>MRD positive</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients aged 18y+ with R/R or MRD+ BCP-ALL treated in the French GRAALL Network&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patient with Philadelphia-negative or positive (Ph+) ALL in relapse, refractory to salvage&#xD;
        therapy, or with MRD positive ALL that received blinatumomab in the French ATU program.,&#xD;
&#xD;
          -  Patient treated in the GRAALL network,&#xD;
&#xD;
          -  Patient who does'nt object to participate in the study&#xD;
&#xD;
        Exclusion Criteria :&#xD;
&#xD;
        - none&#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>Nicolas BOISSEL, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>142499643</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Aurélie CABANNES-HAMY, MD</last_name>
    <phone>142385127</phone>
    <phone_ext>33</phone_ext>
    <email>aurelie.cabannes@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nicolas BOISSEL, MD</last_name>
    <phone>142499643</phone>
    <phone_ext>33</phone_ext>
    <email>nicolas.boissel@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CABANNES-HAMY Aurélie</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aurélie CABANNES-HAMY, MD</last_name>
      <email>aurelie.cabannes@aphp.fr</email>
    </contact>
    <contact_backup>
      <last_name>Nicolas BOISSEL, MD</last_name>
      <email>nicolas.boissel@aphp.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Aurélie CABANNES-HAMY</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicolas BOISSEL</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Dombret H, Cluzeau T, Huguet F, Boissel N. Pediatric-like therapy for adults with ALL. Curr Hematol Malig Rep. 2014 Jun;9(2):158-64. doi: 10.1007/s11899-014-0210-9.</citation>
    <PMID>24682859</PMID>
  </reference>
  <reference>
    <citation>Dhedin N, Huynh A, Maury S, Tabrizi R, Beldjord K, Asnafi V, Thomas X, Chevallier P, Nguyen S, Coiteux V, Bourhis JH, Hichri Y, Escoffre-Barbe M, Reman O, Graux C, Chalandon Y, Blaise D, Schanz U, Lheritier V, Cahn JY, Dombret H, Ifrah N; GRAALL group. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood. 2015 Apr 16;125(16):2486-96; quiz 2586. doi: 10.1182/blood-2014-09-599894. Epub 2015 Jan 13.</citation>
    <PMID>25587040</PMID>
  </reference>
  <reference>
    <citation>Gokbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Huttmann A, Kobbe G, Kreuzer KA, Leimer L, Reichle A, Schaich M, Schwartz S, Serve H, Starck M, Stelljes M, Stuhlmann R, Viardot A, Wendelin K, Freund M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012 Sep 6;120(10):2032-41. doi: 10.1182/blood-2011-12-399287. Epub 2012 Apr 4.</citation>
    <PMID>22493293</PMID>
  </reference>
  <reference>
    <citation>Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foa R, Litzow M, Ribera JM, Rambaldi A, Schiller G, Bruggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015 Jan;16(1):57-66. doi: 10.1016/S1470-2045(14)71170-2. Epub 2014 Dec 16. Erratum In: Lancet Oncol. 2015 Apr;16(4):e158.</citation>
    <PMID>25524800</PMID>
  </reference>
  <reference>
    <citation>Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22. Erratum In: Blood. 2019 Jun 13;133(24):2625.</citation>
    <PMID>29358182</PMID>
  </reference>
  <reference>
    <citation>Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29. Erratum In: Blood. 2015 Aug 20;126(8):1048. Dosage error in article text. Blood. 2016 Sep 15;128(11):1533.</citation>
    <PMID>24876563</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>October 11, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>November 20, 2018</last_update_submitted>
  <last_update_submitted_qc>November 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>Recurrence</mesh_term>
  </condition_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/NCT03751072
org study id: FRENCH-CYTO
nct id: NCT03751072
lead sponsor: 
collaborator: 
The outcome of young adults (18-60 years) with ALL has been dramatically improved by the use
      of pediatric-inspired trials. About 60% of these young adult patients will be cured at 5
      years. In this context, early evaluation of minimal residual disease (MRD) at complete
      remission has been shown to be one of the most powerful prognostic factor, but also
      predictive of the benefit of allogeneic stem cell transplantation (ASCT). Despite this global
      improvement, about 30% of patients experience a relapse and will be exposed to be refractory
      to salvage therapy or to early disease escape. In adult ALL, the most important prognostic
      factors at relapse are : the time from first CR to relapse, the achievement of a second
      complete remission (CR), and the feasibility of ASCT.

      Blinatumomab is a bispecific T-cell engager that recruits T-cell on CD19 positive blast cells
      and induces anti-leukemic cytotoxicity. In a phase 3 trial in relapse/refractory
      Philadelphia-negative (Ph-) ALL, 43% of patients achieved a CR or CR with partial
      hematological recovery (CRh), with the majority of responses occurring within the first
      cycle. In patients with positive MRD (MRD+) BCP-ALL, blinatumomab resulted in complete MRD
      response in 78% of patients after one cycle.

      Between 2012 and 2016, blinatumomab was available in France for R/R and MRD+ ALL adult
      patients through the French Compassionate Use Program. About 92 adult ALL were treated at
      different stages of the disease in 27 centers.
To evaluate the efficacy of blinatumomab given in the French Compassionate Use Program, in
      term of overall survival in both R/R (first cohort) and MRD positive (second cohort)
      patients.

      To evaluate the efficacy of blinatumomab given in the French Compassionate Use Program, in
      term of CR/CRH in R/R patients, To evaluate the efficacy in term of molecular response in
      both R/R and MRD+ cohorts, To evaluate the efficacy of blinatumomab given in the French
      Compassionate Use Program, in both Ph+/Ph- ALL patients To evaluate the feasibility and the
      safety of blinatumomab administration in a multi-center setting.To evaluate the feasibility
      of allogeneic stem cell transplant after blinatumomab administration in both populations.
observational model: Case-Only
time perspective: Retrospective
measure: Overall Survival in R/R and MRD+ cohorts
time frame: 6 months
description: Months
measure: Response rates
time frame: 6 months
description: Percent
measure: Adverse events
time frame: 6 months
description: Percent
measure: Disease free survival
time frame: 6 months
description: Months
arm group label: Relapse/Refractory
arm group label: MRD positive
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nicolas BOISSEL, MD
role: Principal Investigator
affiliation: 142499643
last name: Aurélie CABANNES-HAMY, MD
phone: 142385127
phone ext: 33
email: aurelie.cabannes@aphp.fr
last name: Nicolas BOISSEL, MD
phone: 142499643
phone ext: 33
email: nicolas.boissel@aphp.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: France
citation: Dombret H, Cluzeau T, Huguet F, Boissel N. Pediatric-like therapy for adults with ALL. Curr Hematol Malig Rep. 2014 Jun;9(2):158-64. doi: 10.1007/s11899-014-0210-9.
PMID: 24682859
citation: Dhedin N, Huynh A, Maury S, Tabrizi R, Beldjord K, Asnafi V, Thomas X, Chevallier P, Nguyen S, Coiteux V, Bourhis JH, Hichri Y, Escoffre-Barbe M, Reman O, Graux C, Chalandon Y, Blaise D, Schanz U, Lheritier V, Cahn JY, Dombret H, Ifrah N; GRAALL group. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood. 2015 Apr 16;125(16):2486-96; quiz 2586. doi: 10.1182/blood-2014-09-599894. Epub 2015 Jan 13.
PMID: 25587040
citation: Gokbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Huttmann A, Kobbe G, Kreuzer KA, Leimer L, Reichle A, Schaich M, Schwartz S, Serve H, Starck M, Stelljes M, Stuhlmann R, Viardot A, Wendelin K, Freund M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012 Sep 6;120(10):2032-41. doi: 10.1182/blood-2011-12-399287. Epub 2012 Apr 4.
PMID: 22493293
citation: Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foa R, Litzow M, Ribera JM, Rambaldi A, Schiller G, Bruggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015 Jan;16(1):57-66. doi: 10.1016/S1470-2045(14)71170-2. Epub 2014 Dec 16. Erratum In: Lancet Oncol. 2015 Apr;16(4):e158.
PMID: 25524800
citation: Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22. Erratum In: Blood. 2019 Jun 13;133(24):2625.
PMID: 29358182
citation: Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29. Erratum In: Blood. 2015 Aug 20;126(8):1048. Dosage error in article text. Blood. 2016 Sep 15;128(11):1533.
PMID: 24876563
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Recurrence
sharing ipd: No