<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/NCT03258359</url>
  </required_header>
  <id_info>
    <org_study_id>PACTN-02</org_study_id>
    <nct_id>NCT03258359</nct_id>
  </id_info>
  <brief_title>Personalized Adoptive Cellular Therapy Targeting MDS Stem Cell Neoantigens (PACTN)</brief_title>
  <official_title>A Phase 1 Clinical Trial of Personalized, Adoptive Cellular Immunotherapy Targeting Patient-specific Neoplastic Stem Cell Neoantigens (PACTN) in Patients With Myelodysplastic Syndromes (MDS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PersImmune, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>PersImmune, Inc</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 study will evaluate the safety of autologous T cells that have been immunized ex vivo&#xD;
      with patient-specific MDS stem cell neoantigens in patients with MDS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PACTN is manufactured by a novel method to employ cancer-specific somatic variants&#xD;
      (mutations) as a means to immunize autologous T lymphocytes to specifically kill cancer cells&#xD;
      bearing the protein products of the mutations.&#xD;
&#xD;
      The PACTN method is based on the premise that somatic DNA mutations that cause cancer often&#xD;
      give rise to proteins with an altered amino acid sequence. Peptides derived from these&#xD;
      proteins, if expressed in the context of MHC Class I or II may be perceived as &quot;non-self&quot; by&#xD;
      the immune system; that is, they may be perceived as neoantigens (aka, neoepitopes). Such&#xD;
      neoantigens could therefore serve as immunogenic targets for the development of&#xD;
      patient-specific, personalized T cell mediated immunotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2020</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>Acute and subacute toxicities and AEs</measure>
    <time_frame>baseline to four weeks after infusion</time_frame>
    <description>The incidence of dose limiting toxicities (DLTs) after PACTN infusion will be used to determine the maximum tolerated dose (MTD). Adverse effects (AEs) and in particular cytokine release syndrome (CRS) and potential autoimmune AEs will be monitored.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Persistence, abundance, and activity of PACTN</measure>
    <time_frame>Samples will be collected on days 1, 4, 8, 15, 36, and 57, and then 3, 6, and 12 months</time_frame>
    <description>Determined by quantity of PACTN in the subject's blood sample, assessed by the unique phenotype of PACTN lymphocytes and by functional measurement of PACTN activity (antigen-specific cytotoxicity)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Response</measure>
    <time_frame>Samples will be collected between day 29 and 43, and then at 3, 6, and 12 months</time_frame>
    <description>Disease response will be assessed by International Working Group (IWG) criteria on bone marrow aspiration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall and progression-free survival of subjects who receive PACTN</measure>
    <time_frame>Six and 12 months after PACTN infusion</time_frame>
    <description>Incidence of subjects who are alive, and both alive and disease - free will be assessed at 6 and 12 months</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The duration of hematologic response, if any</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Assessed by measurements of blood counts during subject follow-up, employing IWG criteria</description>
  </other_outcome>
  <other_outcome>
    <measure>PACTN persistence or peak abundance and clinical response</measure>
    <time_frame>6 months and 1 year</time_frame>
    <description>The grouped data on the clinical response and the 6 month and 1-year survival will be analyzed to assess if there is an association between PACTN persistence or peak abundance in blood, and either extent or duration of clinical response or subject survival</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in Variant allele frequency (VAF) of somatic mutations targeted by PACTN</measure>
    <time_frame>From 4 days up to 1 year</time_frame>
    <description>VAFs of targeted mutations will be assessed in blood and marrow after PACTN infusion</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>PACTN</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open label 3+3 dose escalation phase 1 trial; 200 to 1000 mL of immunized T cells infused at 0.3, 1, and 3 x 10e7 nucleated cells/kg body weight.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PACTN</intervention_name>
    <description>To treat patients with MDS who have failed treatment with hypomethylating agents or have relapsed after treatment with hypomethylating agents or have declined hypomethylating therapy.</description>
    <arm_group_label>PACTN</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of MDS according to the French-American-British (FAB) criteria.&#xD;
             Subjects with MDS must have intermediate, high, or very high risk IPSS-R scores and&#xD;
             cytopenia of at least one lineage.&#xD;
&#xD;
          -  Relapsed/refractory disease, or inadequate response to at least 6 cycles of&#xD;
             hypomethylating (HMA) therapy or subjects who decline HMA therapy. Subjects must not&#xD;
             have received any MDS or AML directed therapy for &gt;28 days prior to receiving the&#xD;
             study treatment.&#xD;
&#xD;
          -  Subjects who have opted not to undergo allogeneic hematopoietic stem cell&#xD;
             transplantation or for whom no donor is available and who are not deemed eligible for&#xD;
             high intensity chemotherapy.&#xD;
&#xD;
          -  Age &gt;18 year at the time of obtaining informed consent, male or female.&#xD;
&#xD;
          -  An Eastern Cooperative Oncology Grou (ECOG) performance status score of 0, 1, or 2.&#xD;
&#xD;
          -  Adequate organ function.&#xD;
&#xD;
          -  Seronegative test for HIV-1/2 and hepatitis C antibodies (HCV), and a negative test&#xD;
             for Hepatitis B antigen (HBsAg). If hepatitis C antibody test is positive, then the&#xD;
             subject must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.&#xD;
&#xD;
          -  Women of childbearing potential must have negative pregnancy test prior to initiating&#xD;
             study treatment.&#xD;
&#xD;
          -  Life expectancy &gt;6 months at time of screening.&#xD;
&#xD;
          -  Ability to adhere to the protocol requirements and study visit schedule.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who anticipate use of other investigational or non-investigational agents for&#xD;
             the treatment of MDS during the study period, aside from a stable dose of&#xD;
             erythropoietin stimulating agent started &gt;8 weeks prior to screening for this study.&#xD;
&#xD;
          -  Subjects who have received investigational agents, cytotoxic chemotherapy, or&#xD;
             radiotherapy within 28 days prior to entering the study, or who have not recovered&#xD;
             from AEs dur to agents administered more than 28 days earlier.&#xD;
&#xD;
          -  Subjects who are less than 21 days from surgery or have insufficient recovery from&#xD;
             surgical-related trauma or wound healing.&#xD;
&#xD;
          -  Prior history of allogeneic hematopoietic stem cell transplantation.&#xD;
&#xD;
          -  Current use of granulocyte colony-stimulating factory (G-CSF) or GM-CSF.&#xD;
&#xD;
          -  History of major organ autoimmune disease.&#xD;
&#xD;
          -  Concurrent immunosuppressive therapy. A stable dose of prednisone &lt;10 mg daily or&#xD;
             inhaled corticosteroids are allowed.&#xD;
&#xD;
          -  Any form of primary immunodeficiency.&#xD;
&#xD;
          -  Active bacillus tuberculosis (TB) or any other active or uncontrolled infection.&#xD;
&#xD;
          -  Pior history of treated malignancy in the past 2 years. Subjects with non-melanoma&#xD;
             skin cancer, localized prostate cancer, and carcinoma in situ of the breast of cervix&#xD;
             are allowed.&#xD;
&#xD;
          -  Impaired cardiac function.&#xD;
&#xD;
          -  Pregnant women are excluded from this study as the proposed treatment has not been&#xD;
             well studied in pregnant subjects.&#xD;
&#xD;
          -  Any other medical or psychiatric disorders, or social situation, that would, in the&#xD;
             investigator's opinion, place the subject at unacceptable risk if he/she participates&#xD;
             in the study.&#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>Antonella Vitiello, PhD</last_name>
    <role>Study Director</role>
    <affiliation>PersImmune, Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>March 3, 2020</last_update_submitted>
  <last_update_submitted_qc>March 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MDS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</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/NCT03258359
org study id: PACTN-02
nct id: NCT03258359
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety of autologous T cells that have been immunized ex vivo
      with patient-specific MDS stem cell neoantigens in patients with MDS.
PACTN is manufactured by a novel method to employ cancer-specific somatic variants
      (mutations) as a means to immunize autologous T lymphocytes to specifically kill cancer cells
      bearing the protein products of the mutations.

      The PACTN method is based on the premise that somatic DNA mutations that cause cancer often
      give rise to proteins with an altered amino acid sequence. Peptides derived from these
      proteins, if expressed in the context of MHC Class I or II may be perceived as "non-self" by
      the immune system; that is, they may be perceived as neoantigens (aka, neoepitopes). Such
      neoantigens could therefore serve as immunogenic targets for the development of
      patient-specific, personalized T cell mediated immunotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Acute and subacute toxicities and AEs
time frame: baseline to four weeks after infusion
description: The incidence of dose limiting toxicities (DLTs) after PACTN infusion will be used to determine the maximum tolerated dose (MTD). Adverse effects (AEs) and in particular cytokine release syndrome (CRS) and potential autoimmune AEs will be monitored.
measure: Persistence, abundance, and activity of PACTN
time frame: Samples will be collected on days 1, 4, 8, 15, 36, and 57, and then 3, 6, and 12 months
description: Determined by quantity of PACTN in the subject's blood sample, assessed by the unique phenotype of PACTN lymphocytes and by functional measurement of PACTN activity (antigen-specific cytotoxicity)
measure: Disease Response
time frame: Samples will be collected between day 29 and 43, and then at 3, 6, and 12 months
description: Disease response will be assessed by International Working Group (IWG) criteria on bone marrow aspiration
measure: Overall and progression-free survival of subjects who receive PACTN
time frame: Six and 12 months after PACTN infusion
description: Incidence of subjects who are alive, and both alive and disease - free will be assessed at 6 and 12 months
measure: The duration of hematologic response, if any
time frame: Up to 12 months
description: Assessed by measurements of blood counts during subject follow-up, employing IWG criteria
measure: PACTN persistence or peak abundance and clinical response
time frame: 6 months and 1 year
description: The grouped data on the clinical response and the 6 month and 1-year survival will be analyzed to assess if there is an association between PACTN persistence or peak abundance in blood, and either extent or duration of clinical response or subject survival
measure: Changes in Variant allele frequency (VAF) of somatic mutations targeted by PACTN
time frame: From 4 days up to 1 year
description: VAFs of targeted mutations will be assessed in blood and marrow after PACTN infusion
arm group label: PACTN
arm group type: Experimental
description: Open label 3+3 dose escalation phase 1 trial; 200 to 1000 mL of immunized T cells infused at 0.3, 1, and 3 x 10e7 nucleated cells/kg body weight.
intervention type: Biological
intervention name: PACTN
description: To treat patients with MDS who have failed treatment with hypomethylating agents or have relapsed after treatment with hypomethylating agents or have declined hypomethylating therapy.
arm group label: PACTN
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antonella Vitiello, PhD
role: Study Director
affiliation: PersImmune, Inc
facility: 
country: United States
responsible party type: Sponsor
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome