<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/NCT02187354</url>
  </required_header>
  <id_info>
    <org_study_id>20130320</org_study_id>
    <secondary_id>2014-001700-21</secondary_id>
    <nct_id>NCT02187354</nct_id>
  </id_info>
  <brief_title>Expanded Access Protocol - Blinatumomab in Pediatric &amp; Adolescent Subjects With Relapsed/Refractory B-precursor ALL</brief_title>
  <acronym>RIALTO</acronym>
  <official_title>An Open-Label, Multi-center, Expanded Access Protocol of Blinatumomab for the Treatment of Pediatric and Adolescent Subjects With Relapsed and/or Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</source>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To estimate the incidence of treatment-emergent and treatment-related adverse events during&#xD;
      treatment with blinatumomab in pediatric and adolescent subjects with B-precursor ALL in&#xD;
      second or later bone marrow relapse, in any marrow relapse after alloHSCT, or refractory to&#xD;
      other treatments&#xD;
&#xD;
      Secondary Objective(s):&#xD;
&#xD;
      To describe key efficacy outcomes, including incidence of complete response (CR) within 2&#xD;
      cycles of blinatumomab, minimal residual disease (MRD) remission within 2 cycles of&#xD;
      blinatumomab, relapse free survival (RFS), overall survival (OS), incidence of alloHSCT, and&#xD;
      100-day mortality after alloHSCT.&#xD;
&#xD;
      Hypotheses:&#xD;
&#xD;
      A formal statistical hypothesis will not be tested. The incidence of treatment-emergent and&#xD;
      treatment-related adverse events will be estimated.&#xD;
&#xD;
      Study Endpoints:&#xD;
&#xD;
        -  Incidence of treatment-emergent and treatment-related adverse events&#xD;
&#xD;
        -  Incidence of CR within 2 cycles of blinatumomab&#xD;
&#xD;
        -  MRD remission within 2 cycles of blinatumomab&#xD;
&#xD;
        -  RFS&#xD;
&#xD;
        -  OS&#xD;
&#xD;
        -  Incidence of alloHSCT&#xD;
&#xD;
        -  100-day mortality after alloHSCT&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
      Multi-center, open-label, single-arm expanded access protocol&#xD;
    </textblock>
  </brief_summary>
  <overall_status>No longer available</overall_status>
  <study_type>Expanded Access</study_type>
  <has_expanded_access>No</has_expanded_access>
  <expanded_access_info>
    <expanded_access_type_treatment>Yes</expanded_access_type_treatment>
  </expanded_access_info>
  <condition>Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Blinatumomab</intervention_name>
    <description>A single cycle of blinatumomab (CIVI) treatment is 6wks, 4wks of treatment followed by a 2wk treatment-free interval. Up to 5 cycles will be administered per subject. In the first cycle, for patients with an M3 bone marrow, the initial dose will be 5μg/m2/day for the first 7days, escalated to 15μg/m2/day on D8-D29. For all subsequent cycles 15μg/m2/day will be the dose for all 4wks of continuous treatment. In case of M2 bone marrow or M1 bone marrow with an MRD relapse at screening, the initial dose will start at 15μg/m2/day for the first 7days of treatment &amp; no dose step at D8. For all subsequent cycles the dose will remain 15μg/m2/day. A dose of 9μg/day for the initial dose (if applicable) &amp; 28μg/day for the escalated dose after dose step should not be exceeded.</description>
    <other_name>AMG103, Blincyto</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Extension of LTFU as per ProtocolAmendment7 7Jun18</intervention_name>
    <description>LTFU (Long Term Follow-Up) will extend past 18 months for patients already ended the study/still on study or to be enrolled at European sites if they did not receive a transplantation after blinatumomab treatment. For subjects to be included in the additional LTFU, data will be captured until subjects are 18yrs old (every 6 months by phone contact). The following will be captured: relapse (medullary or extra-medullary relapse and its specific location), second tumor (which type), alive/died and cause of death, hospitalization and reason for hospitalization.</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria 101 Immunophenotypic evidence of CD19 positive B-precursor ALL (pro B-,&#xD;
        pre B-, common ALL) 102 Age &gt; 28 days and &lt; 18 years at the time of informed consent/assent&#xD;
        103 Morphological or molecular evidence of relapsed/refractory disease, defined as one of&#xD;
        the following:&#xD;
&#xD;
          -  Second or later bone marrow relapse (defined as M3 marrow or M2 marrow or M1 marrow&#xD;
             but with MRD level ≥ 10E-3), or&#xD;
&#xD;
          -  Any marrow relapse after alloHSCT (defined as M3 marrow or M2 marrow or M1 marrow but&#xD;
             with and MRD level ≥ 10E-3), or&#xD;
&#xD;
          -  Refractory to other treatments:&#xD;
&#xD;
               -  For patients in first relapse: failure to achieve a CR following a full standard&#xD;
                  reinduction chemotherapy regimen&#xD;
&#xD;
               -  For patients who have not achieved a first remission: failure to achieve&#xD;
                  remission following a full standard induction regimen&#xD;
&#xD;
          -  Subjects previously treated with blinatumomab may be eligible, if subject ended&#xD;
             treatment for reason(s) other than disease progression or intolerability to&#xD;
             blinatumomab (Note: This does not include patients who have already received&#xD;
             blinatumomab treatment on this study, but refers only to patients outside of the&#xD;
             20130320 study)&#xD;
&#xD;
        Other Inclusion Criteria may apply&#xD;
&#xD;
        Exclusion Criteria 201 Any active acute Graft-versus-Host Disease (GvHD) grade 2 to grade 4&#xD;
        according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment&#xD;
        202 Immunosuppresive agents to prevent or treat GvHD within 2 weeks prior to blinatumomab&#xD;
        treatment (except for topical corticosteroids) 203 Active (overt) ALL in the CNS (confirmed&#xD;
        by cerebrospinal fluid [CSF] analysis) or in testes&#xD;
&#xD;
        Other Exclusion Criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Marseille cedex 5</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Paris</city>
        <zip>75019</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Frankfurt am Main</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>München</city>
        <zip>80337</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Münster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Würzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Monza (MB)</city>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Roma</city>
        <zip>00165</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zuerich</city>
        <zip>8032</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <reference>
    <citation>Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, Bourquin JP, Handgretinger R, Brethon B, Rossig C, Kormany WN, Viswagnachar P, Chen-Santel C. Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis. Blood Adv. 2022 Feb 8;6(3):1004-1014. doi: 10.1182/bloodadvances.2021005579.</citation>
    <PMID>34979020</PMID>
  </reference>
  <reference>
    <citation>Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, Bourquin JP, Handgretinger R, Brethon B, Rossig C, Chen-Santel C. Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study. Blood Cancer J. 2020 Jul 24;10(7):77. doi: 10.1038/s41408-020-00342-x. No abstract available. Erratum In: Blood Cancer J. 2021 Feb 1;11(2):28. Blood Cancer J. 2021 Oct 27;11(10):173.</citation>
    <PMID>32709851</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>November 10, 2022</last_update_submitted>
  <last_update_submitted_qc>November 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2022</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Blinatumomab</mesh_term>
  </intervention_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/NCT02187354
org study id: 20130320
secondary id: 2014-001700-21
nct id: NCT02187354
lead sponsor: 
Primary Objective:

      To estimate the incidence of treatment-emergent and treatment-related adverse events during
      treatment with blinatumomab in pediatric and adolescent subjects with B-precursor ALL in
      second or later bone marrow relapse, in any marrow relapse after alloHSCT, or refractory to
      other treatments

      Secondary Objective(s):

      To describe key efficacy outcomes, including incidence of complete response (CR) within 2
      cycles of blinatumomab, minimal residual disease (MRD) remission within 2 cycles of
      blinatumomab, relapse free survival (RFS), overall survival (OS), incidence of alloHSCT, and
      100-day mortality after alloHSCT.

      Hypotheses:

      A formal statistical hypothesis will not be tested. The incidence of treatment-emergent and
      treatment-related adverse events will be estimated.

      Study Endpoints:

        -  Incidence of treatment-emergent and treatment-related adverse events

        -  Incidence of CR within 2 cycles of blinatumomab

        -  MRD remission within 2 cycles of blinatumomab

        -  RFS

        -  OS

        -  Incidence of alloHSCT

        -  100-day mortality after alloHSCT

      Study Design:

      Multi-center, open-label, single-arm expanded access protocol
expanded access type treatment: Yes
intervention type: Drug
intervention name: Blinatumomab
description: A single cycle of blinatumomab (CIVI) treatment is 6wks, 4wks of treatment followed by a 2wk treatment-free interval. Up to 5 cycles will be administered per subject. In the first cycle, for patients with an M3 bone marrow, the initial dose will be 5μg/m2/day for the first 7days, escalated to 15μg/m2/day on D8-D29. For all subsequent cycles 15μg/m2/day will be the dose for all 4wks of continuous treatment. In case of M2 bone marrow or M1 bone marrow with an MRD relapse at screening, the initial dose will start at 15μg/m2/day for the first 7days of treatment & no dose step at D8. For all subsequent cycles the dose will remain 15μg/m2/day. A dose of 9μg/day for the initial dose (if applicable) & 28μg/day for the escalated dose after dose step should not be exceeded.
other name: AMG103, Blincyto
intervention type: Other
intervention name: Extension of LTFU as per ProtocolAmendment7 7Jun18
description: LTFU (Long Term Follow-Up) will extend past 18 months for patients already ended the study/still on study or to be enrolled at European sites if they did not receive a transplantation after blinatumomab treatment. For subjects to be included in the additional LTFU, data will be captured until subjects are 18yrs old (every 6 months by phone contact). The following will be captured: relapse (medullary or extra-medullary relapse and its specific location), second tumor (which type), alive/died and cause of death, hospitalization and reason for hospitalization.
criteria: 
gender: All
minimum age: 0 Years
maximum age: 17 Years
last name: MD
role: Study Director
affiliation: Amgen
facility: 
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country: Austria
country: France
country: Germany
country: Italy
country: Switzerland
country: United Kingdom
country: United States
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
citation: Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, Bourquin JP, Handgretinger R, Brethon B, Rossig C, Kormany WN, Viswagnachar P, Chen-Santel C. Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis. Blood Adv. 2022 Feb 8;6(3):1004-1014. doi: 10.1182/bloodadvances.2021005579.
PMID: 34979020
citation: Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, Bourquin JP, Handgretinger R, Brethon B, Rossig C, Chen-Santel C. Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study. Blood Cancer J. 2020 Jul 24;10(7):77. doi: 10.1038/s41408-020-00342-x. No abstract available. Erratum In: Blood Cancer J. 2021 Feb 1;11(2):28. Blood Cancer J. 2021 Oct 27;11(10):173.
PMID: 32709851
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Blinatumomab