<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/NCT03287804</url>
  </required_header>
  <id_info>
    <org_study_id>AUTO2-MM1</org_study_id>
    <secondary_id>2016-003893-42</secondary_id>
    <nct_id>NCT03287804</nct_id>
  </id_info>
  <brief_title>APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma</brief_title>
  <acronym>APRIL</acronym>
  <official_title>A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients With Relapsed or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Autolus Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Autolus Limited</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test the safety and efficacy of AUTO2, a CAR T Cell Treatment&#xD;
      Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion&#xD;
      phase. Patients with relapsed and relapsed or refractory multiple myeloma will be enrolled in&#xD;
      both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T&#xD;
      cells, which is the starting material for the manufacture of the autologous CAR T product&#xD;
      AUTO2. AUTO2 has a dual target BCMA (B cell maturation antigen) and TACI (Transmembrane&#xD;
      activator and calcium modulator and cyclophilin ligand interactor). Following&#xD;
      pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO2 intravenously&#xD;
      as a single or split dose and will then enter a 12-month follow-up period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Preliminary efficacy seen to date following treatment with AUTO2 has been determined not&#xD;
    sufficient to warrant further development&#xD;
  </why_stopped>
  <start_date type="Actual">May 5, 2017</start_date>
  <completion_date type="Actual">September 5, 2019</completion_date>
  <primary_completion_date type="Actual">September 5, 2019</primary_completion_date>
  <phase>Phase 1/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>Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period</measure>
    <time_frame>Up to 28 days post-infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)</measure>
    <time_frame>Up to 28 days post-infusion</time_frame>
    <description>Dose limiting toxicity was defined as:&#xD;
Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Infused Patients With Best Overall Response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients for Whom an AUTO2 Product Can be Generated</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Feasibility of product generation was examined by assessing the number of AUTO2 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Calculated from the date of first observation of sCR, CR, VGPR or PR to the date of disease progression, relapse or death, for patients who were considered responders (achieved at least PR). Patients who had not progressed, relapsed or died will be censored at the last adequate disease assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Disease Progression</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Calculated from the date of AUTO2 treatment to the date of progression. Patients who had not progressed, relapsed or died without progression/relapse will be censored at the last adequate disease assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Calculated from the date of AUTO2 treatment to the date of progression or death. Patients who have not progressed or relapsed was censored at the last adequate disease assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Descriptive analysis based on number of patients alive at database lock (1-May-2020).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>AUTO2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relapsed or refractory Myeloma patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AUTO2</intervention_name>
    <description>AUTO2 (APRIL CAR T Cells) Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.&#xD;
Following Phase 2 dose determination patients will be treated with selected dose of APRIL CAR T Cells</description>
    <arm_group_label>AUTO2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients, aged ≥ 18.&#xD;
&#xD;
          2. Willing and able to give written, informed consent.&#xD;
&#xD;
          3. Confirmed diagnosis of MM.&#xD;
&#xD;
          4. Measurable disease as defined by IMWG.&#xD;
&#xD;
          5. Relapse or refractory disease and have had at least 3 different prior lines of therapy&#xD;
             including proteasome inhibitor, alkylator and immunomodulatory therapy (IMiD), or have&#xD;
             &quot;double refractory&quot; disease to a proteasome inhibitor and IMiD.&#xD;
&#xD;
          6. For females of childbearing potential, a negative serum or urine pregnancy test must&#xD;
             be documented at screening and confirmed before receiving study treatment.&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.&#xD;
&#xD;
          8. Peripheral blood total lymphocyte count &gt; 0.5 x 10⁹/L.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Women who are pregnant or lactating.&#xD;
&#xD;
          2. Prior treatment with investigational or approved gene therapy or cell therapy&#xD;
             products.&#xD;
&#xD;
          3. Patient has previously received an allogenic stem cell transplant.&#xD;
&#xD;
          4. Clinically significant, uncontrolled heart disease or a recent (within 6 months)&#xD;
             cardiac event.&#xD;
&#xD;
          5. Left Ventricular Ejection fraction &lt; 50 unless the institutional lower limit of normal&#xD;
             is lower.&#xD;
&#xD;
          6. Significant liver disease: alanine aminotransferase (ALT) or aspartate&#xD;
             aminotransferase (AST) ≥ 3 × ULN, or total bilirubin &gt; 2.0 mg/dL or evidence of end&#xD;
             stage liver disease (e.g. ascites, hepatic encephalopathy).&#xD;
&#xD;
          7. Chronic renal impairment requiring dialysis, or calculated creatinine clearance &lt; 30&#xD;
             mL/min&#xD;
&#xD;
          8. Active infectious bacterial or viral disease (hepatitis B virus, hepatitis C virus,&#xD;
             human immunodeficiency virus, human T-lymphotropic virus or syphilis) requiring&#xD;
             treatmenUse of rituximab within the last 3 months.&#xD;
&#xD;
          9. Active autoimmune disease requiring immunosuppression.&#xD;
&#xD;
         10. Received any anti-myeloma therapy within the last 21 days prior to preconditioning or&#xD;
             10 days prior to leukapheresis; steroids of up to 160 mg of dexamethasone are&#xD;
             permitted so long as &gt; 7 days post-dose prior to pre-conditioning or leukapheresis.&#xD;
&#xD;
         11. Known allergy to albumin, dimethyl sulfoxide (DMSO), cyclophosphamide or fludarabine.&#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>Autolus Limited</last_name>
    <role>Study Director</role>
    <affiliation>Sponsor GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VU University Medical Centre Amsterdam</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>September 4, 2020</results_first_submitted>
  <results_first_submitted_qc>September 30, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 23, 2020</results_first_posted>
  <last_update_submitted>September 30, 2020</last_update_submitted>
  <last_update_submitted_qc>September 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Relapsed Multiple Myeloma</keyword>
  <keyword>Refractory Multiple Myeloma</keyword>
  <keyword>AUTO2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03287804/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 21, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03287804/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients were treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.</recruitment_details>
      <pre_assignment_details>Screening procedures were performed up to 12 weeks before study treatment administered</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AUTO2</title>
          <description>Relapsed or refractory myeloma patients.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Leukaperesed</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Started Pre-conditioning Therapy</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Study Treatment</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>AUTO2</title>
          <description>Relapsed or refractory myeloma patients</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Netherlands</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period</title>
        <time_frame>Up to 28 days post-infusion</time_frame>
        <population>Patients who received at least 1 dose (complete or partial) of AUTO2 therapy (infused set)</population>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period</title>
          <population>Patients who received at least 1 dose (complete or partial) of AUTO2 therapy (infused set)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)</title>
        <description>Dose limiting toxicity was defined as:&#xD;
Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.</description>
        <time_frame>Up to 28 days post-infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)</title>
          <description>Dose limiting toxicity was defined as:&#xD;
Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Infused Patients With Best Overall Response</title>
        <description>Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations</description>
        <time_frame>Up to 2 years</time_frame>
        <population>All patients who received at least 1 dose (complete or partial) of AUTO2 therapy in Phase I of the study were included in this analysis. No patients were enrolled in Phase II as the study was early terminated in Phase I. 2 patients were retreated; their best overall response is presented for this endpoint</population>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Infused Patients With Best Overall Response</title>
          <description>Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations</description>
          <population>All patients who received at least 1 dose (complete or partial) of AUTO2 therapy in Phase I of the study were included in this analysis. No patients were enrolled in Phase II as the study was early terminated in Phase I. 2 patients were retreated; their best overall response is presented for this endpoint</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Patients for Whom an AUTO2 Product Can be Generated</title>
        <description>Feasibility of product generation was examined by assessing the number of AUTO2 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).</description>
        <time_frame>Up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients for Whom an AUTO2 Product Can be Generated</title>
          <description>Feasibility of product generation was examined by assessing the number of AUTO2 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate</title>
        <description>Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2</description>
        <time_frame>Up to 2 years</time_frame>
        <population>All patients who received at least 1 dose (complete or partial) of AUTO2 therapy in Phase I of the study were included in this analysis. 2 patients were retreated; their best overall response is presented for this endpoint</population>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate</title>
          <description>Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2</description>
          <population>All patients who received at least 1 dose (complete or partial) of AUTO2 therapy in Phase I of the study were included in this analysis. 2 patients were retreated; their best overall response is presented for this endpoint</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Calculated from the date of first observation of sCR, CR, VGPR or PR to the date of disease progression, relapse or death, for patients who were considered responders (achieved at least PR). Patients who had not progressed, relapsed or died will be censored at the last adequate disease assessment.</description>
        <time_frame>Up to 2 years</time_frame>
        <population>Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the duration of response. The study was terminated early and Phase 2 was not started.</population>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Calculated from the date of first observation of sCR, CR, VGPR or PR to the date of disease progression, relapse or death, for patients who were considered responders (achieved at least PR). Patients who had not progressed, relapsed or died will be censored at the last adequate disease assessment.</description>
          <population>Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the duration of response. The study was terminated early and Phase 2 was not started.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Disease Progression</title>
        <description>Calculated from the date of AUTO2 treatment to the date of progression. Patients who had not progressed, relapsed or died without progression/relapse will be censored at the last adequate disease assessment.</description>
        <time_frame>Up to 2 years</time_frame>
        <population>Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the time to disease progression. The study was terminated early and Phase 2 was not started.</population>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Disease Progression</title>
          <description>Calculated from the date of AUTO2 treatment to the date of progression. Patients who had not progressed, relapsed or died without progression/relapse will be censored at the last adequate disease assessment.</description>
          <population>Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the time to disease progression. The study was terminated early and Phase 2 was not started.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Calculated from the date of AUTO2 treatment to the date of progression or death. Patients who have not progressed or relapsed was censored at the last adequate disease assessment</description>
        <time_frame>Up to 2 years</time_frame>
        <population>Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the progression-free survival. The study was terminated early and Phase 2 was not started.</population>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Calculated from the date of AUTO2 treatment to the date of progression or death. Patients who have not progressed or relapsed was censored at the last adequate disease assessment</description>
          <population>Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the progression-free survival. The study was terminated early and Phase 2 was not started.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Descriptive analysis based on number of patients alive at database lock (1-May-2020).</description>
        <time_frame>Up to 2 years</time_frame>
        <population>All patients who receive at least 1 dose (complete or partial dose) of AUTO2 therapy</population>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Descriptive analysis based on number of patients alive at database lock (1-May-2020).</description>
          <population>All patients who receive at least 1 dose (complete or partial dose) of AUTO2 therapy</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood</title>
        <description>Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.</description>
        <time_frame>Up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>AUTO2</title>
            <description>Relapsed or refractory myeloma patients</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood</title>
          <description>Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Day 0 until Day 60 post last AUTO2 infusion.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AUTO2</title>
          <description>Relapsed or refractory myeloma patients</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (22.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metaplastic breast carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Hedache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (22.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="31" subjects_affected="9" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="29" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site bruise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="10" subjects_affected="6" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemophagocytic lymphohistiocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterovirus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>External ear cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Metapneumovirus infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Parvovirus B19 infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pseudomonal bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rhinovirus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Urinary tract infection enterococcal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALT increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>AST increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood ALP increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood creatinine phosphokinase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="71" subjects_affected="7" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Respiratory syncytial virus test positive</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Serum ferritin increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Musculoskeletal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tension headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Micturition urgency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tachypnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Early termination leading to small numbers of patients analyzed</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Clinical Project Manager</name_or_title>
      <organization>Autolus Ltd</organization>
      <phone>+44 1483 920748</phone>
      <email>clinicaltrials@autolus.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03287804
org study id: AUTO2-MM1
secondary id: 2016-003893-42
nct id: NCT03287804
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test the safety and efficacy of AUTO2, a CAR T Cell Treatment
      Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma.
The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion
      phase. Patients with relapsed and relapsed or refractory multiple myeloma will be enrolled in
      both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T
      cells, which is the starting material for the manufacture of the autologous CAR T product
      AUTO2. AUTO2 has a dual target BCMA (B cell maturation antigen) and TACI (Transmembrane
      activator and calcium modulator and cyclophilin ligand interactor). Following
      pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO2 intravenously
      as a single or split dose and will then enter a 12-month follow-up period.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period
time frame: Up to 28 days post-infusion
measure: Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)
time frame: Up to 28 days post-infusion
description: Dose limiting toxicity was defined as:
Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.
measure: Number of Infused Patients With Best Overall Response
time frame: Up to 2 years
description: Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations
measure: Proportion of Patients for Whom an AUTO2 Product Can be Generated
time frame: Up to 2 years
description: Feasibility of product generation was examined by assessing the number of AUTO2 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).
measure: Clinical Benefit Rate
time frame: Up to 2 years
description: Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2
measure: Duration of Response
time frame: Up to 2 years
description: Calculated from the date of first observation of sCR, CR, VGPR or PR to the date of disease progression, relapse or death, for patients who were considered responders (achieved at least PR). Patients who had not progressed, relapsed or died will be censored at the last adequate disease assessment.
measure: Time to Disease Progression
time frame: Up to 2 years
description: Calculated from the date of AUTO2 treatment to the date of progression. Patients who had not progressed, relapsed or died without progression/relapse will be censored at the last adequate disease assessment.
measure: Progression-free Survival
time frame: Up to 2 years
description: Calculated from the date of AUTO2 treatment to the date of progression or death. Patients who have not progressed or relapsed was censored at the last adequate disease assessment
measure: Overall Survival
time frame: Up to 2 years
description: Descriptive analysis based on number of patients alive at database lock (1-May-2020).
measure: Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood
time frame: Up to 2 years
description: Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.
arm group label: AUTO2
arm group type: Experimental
description: Relapsed or refractory Myeloma patients
intervention type: Biological
intervention name: AUTO2
description: AUTO2 (APRIL CAR T Cells) Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.
Following Phase 2 dose determination patients will be treated with selected dose of APRIL CAR T Cells
arm group label: AUTO2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Autolus Limited
role: Study Director
affiliation: Sponsor GmbH
facility: 
facility: 
facility: 
facility: 
country: Netherlands
country: United Kingdom
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Early termination leading to small numbers of patients analyzed
point of contact: 