<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/NCT02989064</url>
  </required_header>
  <id_info>
    <org_study_id>ADP-0022-004</org_study_id>
    <nct_id>NCT02989064</nct_id>
  </id_info>
  <brief_title>MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers</brief_title>
  <official_title>Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10ᶜ⁷⁹⁶T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adaptimmune</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Adaptimmune</source>
  <brief_summary>
    <textblock>
      This Phase 1 study is designed as a cell dose escalation trial in HLA-A*02:01 and HLA-A*02:06&#xD;
      subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will&#xD;
      enroll subjects between the ages of 18 and 75 using a modified 3+3 cell dose escalation&#xD;
      design, to evaluate dose limiting toxicities and determine the target cell dose range.&#xD;
      Following the dose escalation phase, additional subjects will be enrolled at the target cell&#xD;
      dose range to further characterize safety and the effects at this cell dose.&#xD;
&#xD;
      The study will take the subject's T cells, which are a natural type of immune cell in the&#xD;
      blood, and send them to a laboratory to be modified. The changed T cells used in this study&#xD;
      will be the subject's own T cells that have been genetically changed with the aim of&#xD;
      attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects&#xD;
      will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by&#xD;
      T cell infusion. The purpose of this study is to test the safety of genetically changed T&#xD;
      cells and find out what effects, if any, they have in subjects with urothelial, melanoma or&#xD;
      head and neck cancer.&#xD;
&#xD;
      Subjects will be seen frequently by the Study Physician after receiving their T cells for the&#xD;
      next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the&#xD;
      Schedule of Procedures. All subjects completing or withdrawing from the interventional&#xD;
      portion of the study will enter a long term follow-up phase for observation of delayed&#xD;
      adverse events and overall survival for 15 years post-infusion.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">June 4, 2020</completion_date>
  <primary_completion_date type="Actual">December 18, 2019</primary_completion_date>
  <phase>Phase 1</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>Number of subjects with adverse events (AE), including serious adverse events (SAE).</measure>
    <time_frame>3 years</time_frame>
    <description>Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation; and cardiac assessments, including ECG/troponin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of the persistence of genetically modified T cells</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of the persistence of the infused T cells in the periphery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of RCL in genetically modified T cells.</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of RCL in Subject PBMCs using PCR-based assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of dose limiting toxicities to determine optimally tolerated dose range</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of dose limiting toxicities will be performed using the CTCAE Version 4.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of the efficacy of the treatment by assessment of time to first response.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of the efficacy of the treatment by assessment of duration of response.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause.</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of the efficacy of the treatment by assessment of duration of stable disease.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of the efficacy of the treatment by assessment of progression-free survival.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Interval between the date of first T cell infusion and date of death due to any cause.</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of the efficacy of the treatment by assessment of overall survival.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)</measure>
    <time_frame>15 years post last treatment (infusion)</time_frame>
    <description>New occurrence of any malignancy&#xD;
New occurrence or exacerbation of a pre-existing neurologic disorder&#xD;
New occurrence or exacerbation of a prior rheumatologic or other autoimmune disorder&#xD;
New occurrence of a hematologic disorder&#xD;
New occurrence of any opportunistic and/or serious infections&#xD;
New occurrence of any unanticipated illness and/or hospitalization deemed related to gene modified cell therapy</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Urothelial Carcinoma</condition>
  <condition>Head and Neck Cancer</condition>
  <condition>Melanoma</condition>
  <condition>Bladder Urothelial Carcinoma</condition>
  <arm_group>
    <arm_group_label>Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells</intervention_name>
    <description>Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1</description>
    <arm_group_label>Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is ≥18 to ≤75 years of age at the time of signing the study informed consent.&#xD;
&#xD;
          2. Subject has histologically confirmed diagnosis of any one of the following cancers:&#xD;
             (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal&#xD;
             pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.&#xD;
&#xD;
          3. Subject is HLA-A*02:01 and/or HLA-A*02:06 positive.&#xD;
&#xD;
          4. Subject has measurable disease according to RECIST v1.1 criteria prior to&#xD;
             lymphodepletion&#xD;
&#xD;
          5. Subject meets disease-specific requirements per protocol&#xD;
&#xD;
          6. Subject has anticipated life expectancy &gt; 6 months prior to leukapheresis and &gt;3&#xD;
             months prior to lymphodepletion.&#xD;
&#xD;
          7. Subject's tumor shows positive MAGE-A10 expression&#xD;
&#xD;
          8. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.&#xD;
&#xD;
          9. Subject has a left ventricular ejection fraction ≥50%.&#xD;
&#xD;
         10. Subject is fit for leukapheresis and has adequate venous access for the cell&#xD;
             collection.&#xD;
&#xD;
         11. Female subject of childbearing potential (FCBP) must have a negative urine or serum&#xD;
             pregnancy test or male subject must be surgically sterile or agree to use a double&#xD;
             barrier contraception method or abstain from heterosexual activity with a female of&#xD;
             childbearing potential starting at the first dose of chemotherapy and for 4 months&#xD;
             thereafter.&#xD;
&#xD;
         12. Subject must have adequate organ function per protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject is HLA-A*02:05 in either allele, HLA-B*15:01 and/or HLA-B*46:01 positive.&#xD;
             Subject has any A*02 null allele (designated with an &quot;N&quot;, e.g. A*02:32N) as the sole&#xD;
             HLA-A*02 allele.&#xD;
&#xD;
          2. Subject has received or plans to receive excluded therapy/treatment prior to&#xD;
             leukapheresis or lymphodepleting chemotherapy per protocol&#xD;
&#xD;
          3. Subject that has toxicity from previous anti-cancer therapy must have recovered to ≤&#xD;
             Grade 1 prior to enrollment&#xD;
&#xD;
          4. Subject has history of allergic reactions attributed to compounds of similar chemical&#xD;
             or biologic composition to fludarabine, cyclophosphamide or other agents used in the&#xD;
             study.&#xD;
&#xD;
          5. Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should&#xD;
             have been fully recovered from any surgical related toxicities.&#xD;
&#xD;
          6. Subject has an electrocardiogram (ECG) showing clinically significant abnormality at&#xD;
             Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in&#xD;
             females (≥480 msec for subjects with bundle branch block [BBB]) over 3 consecutive&#xD;
             ECGs. Either Fridericia's or Bazett's formula may be used to correct the QT interval.&#xD;
&#xD;
          7. Subject has symptomatic CNS metastases.&#xD;
&#xD;
          8. Subject has a history of chronic or recurrent severe autoimmune or immune mediated&#xD;
             disease&#xD;
&#xD;
          9. Subject has any other active malignancy besides the tumor under study within 3 years&#xD;
             prior to Screening.&#xD;
&#xD;
         10. Subject has uncontrolled intercurrent illness&#xD;
&#xD;
         11. Subject has active infection with HIV, HBV, HCV or HTLV&#xD;
&#xD;
         12. Subject is pregnant or breastfeeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Hong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</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>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt - Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</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>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G1X6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Start Madrid-FJD, Fundación Jimѐnez Díaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 Octubre Avda. de Córdoba</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>November 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>December 17, 2020</last_update_submitted>
  <last_update_submitted_qc>December 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cell Therapy</keyword>
  <keyword>T Cell Therapy</keyword>
  <keyword>SPEAR T Cell</keyword>
  <keyword>MAGE-A10</keyword>
  <keyword>Immuno-oncology</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Urothelial Cancer</keyword>
  <keyword>Previously Treated</keyword>
  <keyword>T Cell Receptor</keyword>
  <keyword>Inoperable</keyword>
  <keyword>Advanced</keyword>
  <keyword>Cancer</keyword>
  <keyword>Bladder</keyword>
  <keyword>Head and neck</keyword>
  <keyword>Melanoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</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/NCT02989064
org study id: ADP-0022-004
nct id: NCT02989064
lead sponsor: 
This Phase 1 study is designed as a cell dose escalation trial in HLA-A*02:01 and HLA-A*02:06
      subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will
      enroll subjects between the ages of 18 and 75 using a modified 3+3 cell dose escalation
      design, to evaluate dose limiting toxicities and determine the target cell dose range.
      Following the dose escalation phase, additional subjects will be enrolled at the target cell
      dose range to further characterize safety and the effects at this cell dose.

      The study will take the subject's T cells, which are a natural type of immune cell in the
      blood, and send them to a laboratory to be modified. The changed T cells used in this study
      will be the subject's own T cells that have been genetically changed with the aim of
      attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects
      will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by
      T cell infusion. The purpose of this study is to test the safety of genetically changed T
      cells and find out what effects, if any, they have in subjects with urothelial, melanoma or
      head and neck cancer.

      Subjects will be seen frequently by the Study Physician after receiving their T cells for the
      next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the
      Schedule of Procedures. All subjects completing or withdrawing from the interventional
      portion of the study will enter a long term follow-up phase for observation of delayed
      adverse events and overall survival for 15 years post-infusion.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects with adverse events (AE), including serious adverse events (SAE).
time frame: 3 years
description: Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation; and cardiac assessments, including ECG/troponin.
measure: Evaluation of the persistence of genetically modified T cells
time frame: 3 years
description: Evaluation of the persistence of the infused T cells in the periphery.
measure: Measurement of RCL in genetically modified T cells.
time frame: 3 years
description: Evaluation of RCL in Subject PBMCs using PCR-based assay.
measure: Assessment of dose limiting toxicities to determine optimally tolerated dose range
time frame: 3 years
description: Evaluation of dose limiting toxicities will be performed using the CTCAE Version 4.0
measure: Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).
time frame: 3 years
description: Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
measure: Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.
time frame: 3 years
description: Evaluation of the efficacy of the treatment by assessment of time to first response.
measure: Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.
time frame: 3 years
description: Evaluation of the efficacy of the treatment by assessment of duration of response.
measure: Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause.
time frame: 3 years
description: Evaluation of the efficacy of the treatment by assessment of duration of stable disease.
measure: Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
time frame: 3 years
description: Evaluation of the efficacy of the treatment by assessment of progression-free survival.
measure: Interval between the date of first T cell infusion and date of death due to any cause.
time frame: 3 years
description: Evaluation of the efficacy of the treatment by assessment of overall survival.
measure: Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)
time frame: 15 years post last treatment (infusion)
description: New occurrence of any malignancy
New occurrence or exacerbation of a pre-existing neurologic disorder
New occurrence or exacerbation of a prior rheumatologic or other autoimmune disorder
New occurrence of a hematologic disorder
New occurrence of any opportunistic and/or serious infections
New occurrence of any unanticipated illness and/or hospitalization deemed related to gene modified cell therapy
arm group label: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
arm group type: Experimental
intervention type: Genetic
intervention name: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
description: Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1
arm group label: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: David Hong, MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Melanoma
mesh term: Head and Neck Neoplasms
mesh term: Carcinoma, Transitional Cell