<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/NCT04404660</url>
  </required_header>
  <id_info>
    <org_study_id>FELIX (AUTO1-AL1)</org_study_id>
    <secondary_id>2019-001937-16</secondary_id>
    <nct_id>NCT04404660</nct_id>
  </id_info>
  <brief_title>A Study of CD19 Targeted CAR T Cell Therapy in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL)</brief_title>
  <official_title>An Open-Label, Multi-Centre, Phase Ib/II Study Evaluating the Safety and Efficacy of AUTO1, a CAR T Cell Treatment Targeting CD19, in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia</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>
      This is a Phase Ib/II study to evaluate the safety and efficacy of autologous T cells&#xD;
      engineered with a chimeric antigen receptor (CAR) targeting CD19 in adult patients with&#xD;
      relapsed or refractory B cell acute lymphoblastic leukemia (ALL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase Ib/II, open-label, multi-center, single arm study is designed to evaluate the&#xD;
      safety and efficacy of AUTO1 in adult patients with B-cell ALL by determining the overall&#xD;
      response rate (ORR).&#xD;
&#xD;
      Adult patients with relapsed or refractory ALL will be enrolled in both phases of the study.&#xD;
      Consented patients will go through the following five sequential stages: screening,&#xD;
      leukapheresis, pre-conditioning, treatment, and follow-up. All patients will receive a total&#xD;
      target dose of 410E+6 of CAR T cells as a split dose on Day 1 and on Day 10 (±2 days).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 4, 2020</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2025</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 Ib - Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion</measure>
    <time_frame>Up to 24 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase II - Cohort IIA: ORR defined as proportion of patients achieving CR or CRi as assessed by an IRRC. Cohort IIB: Proportion of patients achieving MRD-negative remission by central ClonoSEQ NGS testing (&lt;1e-4 leukemic cells)</measure>
    <time_frame>Up to 24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase II - Proportion of patients achieving MRD-negative CR by NGS (&lt;1e-4 leukemic cells)</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Complete remission rate</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Response to AUTO1 treatment measured as duration of remission (DOR)</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Response to AUTO1 measured as progression-free survival (PFS).</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II -Response to AUTO1 treatment measured as overall survival (OS)</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Frequency and severity of AEs and SAEs</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Incidence of severe hypogammaglobulinaemia</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Duration of severe hypogammaglobulinaemia</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Detection of CAR T cells measured by PCR following AUTO1 infusion</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">153</enrollment>
  <condition>Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>AUTO1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AUTO1</intervention_name>
    <description>Following pre-conditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with a total target dose of 410E+6 of CD19-positive CAR T cells as a split dose on Day 1 and on Day 10 (±2 days).</description>
    <arm_group_label>AUTO1</arm_group_label>
    <other_name>Obecabtagene autoleucel (obe-cel)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older Age 18 years or older&#xD;
&#xD;
          -  ECOG performance status of 0 or 1&#xD;
&#xD;
          -  Relapsed or refractory B cell ALL&#xD;
&#xD;
          -  Patients with Ph+ ALL are eligible if intolerant to TKI, failed two lines of any TKI,&#xD;
             or failed one line of second-generation TKI, or if TKI is contraindicated&#xD;
&#xD;
          -  Documented CD19 positivity within 1 month of screening&#xD;
&#xD;
          -  Phase Ib: Primary Cohort IA: Presence of ≥5% blasts in BM at screening&#xD;
&#xD;
          -  Phase Ib: Exploratory Cohort IB: MRD-positive defined as ≥ 1e-4 and &lt;5% blasts in the&#xD;
             BM at screening&#xD;
&#xD;
          -  Phase II: Primary Cohort IIA: Presence of ≥5% blasts in BM at screening&#xD;
&#xD;
          -  Phase II: Cohort IIB: ≥2nd CR or CRi with MRD-positive defined as ≥1e-3 by central&#xD;
             ClonoSEQ® NGS testing and &lt;5% blasts in the BM at screening&#xD;
&#xD;
          -  Adequate renal, hepatic, pulmonary, and cardiac function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Phase Ib (Cohort IA and Cohort IB) and Phase II (Cohort IIA and Cohort IIB) B-ALL with&#xD;
             isolated EM disease&#xD;
&#xD;
          -  Diagnosis of Burkitt's leukaemia/lymphoma or CML lymphoid in blast crisis&#xD;
&#xD;
          -  History or presence of clinically relevant CNS pathology&#xD;
&#xD;
          -  Presence of CNS-3 disease or CNS-2 disease with neurological changes&#xD;
&#xD;
          -  Presence of active or uncontrolled fungal, bacterial, viral, or other infection&#xD;
             requiring systemic antimicrobials for management&#xD;
&#xD;
          -  Active or latent Hepatitis B virus or active Hepatitis C virus&#xD;
&#xD;
          -  Human Immunodeficiency Virus (HIV), HTLV-1, HTLV-2, syphilis positive test&#xD;
&#xD;
          -  Prior CD19 targeted therapy other than blinatumomab. Patients who have experienced&#xD;
             Grade 3 or higher neurotoxicity following blinatumomab.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>93534</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego Health (UCSD)</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis (UC Davis)</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco (UCSF)</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute (CBCI)</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H Lee Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute of Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TriStar Centennial Medical Center (SCRI)</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott &amp; White Research Institute</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TTI-Methodist (Texas Transplant Institute) (SCRI)</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacio' Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Fé</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>NW1 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King's College Hospital</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manchester Royal Infirmary Hospital</name>
      <address>
        <city>Manchester</city>
        <state>Greater Manchester</state>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth University Hospital</name>
      <address>
        <city>Glasgow</city>
        <state>Scotland</state>
        <zip>G514TF</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>
        <state>Tyne And Wear</state>
        <zip>NE7 7DN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Birmingham NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B15 2GW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Bristol and Weston NHS Foundation Trust (UHBW)</name>
      <address>
        <city>Bristol</city>
        <zip>BS2 8ED</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 12, 2020</study_first_submitted>
  <study_first_submitted_qc>May 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>August 24, 2023</last_update_submitted>
  <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>B cell acute lymphoblastic leukemia</keyword>
  <keyword>Relapsed B cell acute lymphoblastic leukemia</keyword>
  <keyword>Refractory B cell acute lymphoblastic leukemia</keyword>
  <keyword>ALL</keyword>
  <keyword>AUTO1</keyword>
  <keyword>CD19-positive CAR T cell</keyword>
  <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>
  <!-- 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/NCT04404660
org study id: FELIX (AUTO1-AL1)
secondary id: 2019-001937-16
nct id: NCT04404660
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase Ib/II study to evaluate the safety and efficacy of autologous T cells
      engineered with a chimeric antigen receptor (CAR) targeting CD19 in adult patients with
      relapsed or refractory B cell acute lymphoblastic leukemia (ALL).
This Phase Ib/II, open-label, multi-center, single arm study is designed to evaluate the
      safety and efficacy of AUTO1 in adult patients with B-cell ALL by determining the overall
      response rate (ORR).

      Adult patients with relapsed or refractory ALL will be enrolled in both phases of the study.
      Consented patients will go through the following five sequential stages: screening,
      leukapheresis, pre-conditioning, treatment, and follow-up. All patients will receive a total
      target dose of 410E+6 of CAR T cells as a split dose on Day 1 and on Day 10 (±2 days).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase Ib - Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion
time frame: Up to 24 months
measure: Phase II - Cohort IIA: ORR defined as proportion of patients achieving CR or CRi as assessed by an IRRC. Cohort IIB: Proportion of patients achieving MRD-negative remission by central ClonoSEQ NGS testing (<1e-4 leukemic cells)
time frame: Up to 24 months
measure: Phase II - Proportion of patients achieving MRD-negative CR by NGS (<1e-4 leukemic cells)
time frame: Up to 24 months
measure: Phase II - Complete remission rate
time frame: Up to 24 months
measure: Phase II - Response to AUTO1 treatment measured as duration of remission (DOR)
time frame: Up to 24 months
measure: Phase II - Response to AUTO1 measured as progression-free survival (PFS).
time frame: Up to 24 months
measure: Phase II -Response to AUTO1 treatment measured as overall survival (OS)
time frame: Up to 24 months
measure: Phase II - Frequency and severity of AEs and SAEs
time frame: Up to 24 months
measure: Phase II - Incidence of severe hypogammaglobulinaemia
time frame: Up to 24 months
measure: Phase II - Duration of severe hypogammaglobulinaemia
time frame: Up to 24 months
measure: Phase II - Detection of CAR T cells measured by PCR following AUTO1 infusion
time frame: Up to 24 months
arm group label: AUTO1
arm group type: Experimental
intervention type: Biological
intervention name: AUTO1
description: Following pre-conditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with a total target dose of 410E+6 of CD19-positive CAR T cells as a split dose on Day 1 and on Day 10 (±2 days).
arm group label: AUTO1
other name: Obecabtagene autoleucel (obe-cel)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid