<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/NCT03027102</url>
  </required_header>
  <id_info>
    <org_study_id>OZM-079</org_study_id>
    <nct_id>NCT03027102</nct_id>
  </id_info>
  <brief_title>Study of Allogeneic Double Negative T Cells (DNT-UHN-1) in Patients With High Risk Acute Myeloid Leukemia</brief_title>
  <official_title>Phase I Study of Allogeneic Double Negative T Cells (DNT-UHN-1) in Patients With High Risk Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ozmosis Research Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to determine the safety and toxicity of incremental doses of Double Negative&#xD;
      T (DNT) cells in human subjects with high risk acute myeloid leukemia (AML). DNT cells are&#xD;
      mature T lymphocytes that comprise ~1% of white blood cells in humans. Injection of DNTs from&#xD;
      healthy donors has been demonstrated to be effective against AML cells. DNT cells will be&#xD;
      collected from healthy volunteers and injected into patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 15, 2017</start_date>
  <completion_date type="Anticipated">September 2021</completion_date>
  <primary_completion_date type="Anticipated">September 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with adverse events and abnormal laboratory studies.</measure>
    <time_frame>2 years</time_frame>
    <description>Patients will be assessed for adverse events based upon, but not limited to, monitoring of vital signs and prescribed laboratory studies. Adverse events (AE) will use the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE). This study will utilize the CTCAE Version 4.03 for adverse event reporting.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of cells with disease specific mutations per patient</measure>
    <time_frame>2 years</time_frame>
    <description>Quantitive real time polymerase chain reaction (PCR) analysis for disease specific mutations will be performed on the bone marrow aspirate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leukemia load</measure>
    <time_frame>2 years</time_frame>
    <description>Peripheral blood will be obtained after DNT cell infusion to monitor leukemia load and residual disease by determining the frequency of leukemic cell markers on cells using flow cytometry.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Patient Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive DNT cells from healthy donors.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Donor Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Healthy volunteer donors will donate blood.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DNT cells</intervention_name>
    <description>DNT cells will be expanded (increased in numbers) in the laboratory, in order to enhance their tumour destroying potential before infusion into AML patients.</description>
    <arm_group_label>Patient Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Patient Inclusion Criteria:&#xD;
&#xD;
          1. Patients with AML who are 18 years of age or older.&#xD;
&#xD;
          2. Viably frozen cells from the time of diagnosis or relapse are available for&#xD;
             sensitivity testing to DNT cells.&#xD;
&#xD;
          3. Patients have given informed consent.&#xD;
&#xD;
          4. Patients in remission following FLAG-Ida induction therapy who are receiving&#xD;
             consolidation treatment.&#xD;
&#xD;
          5. Creatinine &lt; 1.5 x ULN within 7 days prior to day 1 of study treatment.&#xD;
&#xD;
          6. AST, ALP, bilirubin &lt; 1.5x ULN within 7 days prior to day 1 of study treatment.&#xD;
&#xD;
          7. Female patients of childbearing potential should be willing to use 2 methods of birth&#xD;
             control (Refer to section 9.2.15 or be surgically sterile, or abstain from&#xD;
             heterosexual activity for the course of the study from day 1 until 1 months following&#xD;
             chemotherapy. Patients of childbearing potential are those who have not been&#xD;
             surgically sterilized or have not been free from menses for &gt; 2 years.&#xD;
&#xD;
             Male patients should use condoms or abstain from sex from the time of beginning&#xD;
             chemotherapy to 1 month after the chemotherapy.&#xD;
&#xD;
          8. Patients must be able to comply with study procedures, at the minimum, until all&#xD;
             DNT-UHN-1 cells are out of their system.&#xD;
&#xD;
        Patient Exclusion Criteria:&#xD;
&#xD;
          1. ECOG performance status &lt;2.&#xD;
&#xD;
          2. Patients with a known persistent infection.&#xD;
&#xD;
          3. Patients with known active CNS disease.&#xD;
&#xD;
          4. Life expectancy &lt; 3 months.&#xD;
&#xD;
          5. Patients should be off Cox2 inhibitors and corticosteroids for at least 3 days prior&#xD;
             to and 7 days after infusion of DNT cells.&#xD;
&#xD;
          6. Patients who are HIV positive.&#xD;
&#xD;
          7. Patients for whom healthy donor DNT kill &lt;10% of patient's blast cells.&#xD;
&#xD;
        Donor Inclusion Criteria:&#xD;
&#xD;
          1. Has given written informed consent.&#xD;
&#xD;
          2. Is 18 years of age or older.&#xD;
&#xD;
          3. No known prior blood product transfusion or surgery.&#xD;
&#xD;
          4. Blood electrolytes (Sodium, Potassium, Chloride, Bicarbonate, Magnesium, Phosphate,&#xD;
             Calcium) within normal ranges.&#xD;
&#xD;
          5. Normal complete blood counts.&#xD;
&#xD;
          6. Normal liver and kidney function (Bilirubin, AST, ALT, ALP, LDH, plasma albumin,&#xD;
             creatinine).&#xD;
&#xD;
          7. Negative for transfusion transmissible illnesses (CMV, HIV I/II, HTLV I/II, Hepatitis&#xD;
             B Surface Antigen, Hepatitis B Surface Antibody, Hepatitis B Core Antibody, Hepatitis&#xD;
             C Antibody) within 30 days of blood collection for DNT cell expansion for patient&#xD;
             infusion.&#xD;
&#xD;
          8. Negative for evidence of exposure to West Nile Virus, Syphilis within 30 days of blood&#xD;
             collection for DNT cell expansion for patient infusion.&#xD;
&#xD;
          9. DNT cell expansion yield is &gt;108 per mL blood using the standard protocol. Expanded&#xD;
             DNT cells show ≥20% cytotoxicity to at least 3 AML cell lines (MV4-11 AML3, and U937).&#xD;
&#xD;
         10. The donor who meet all donor inclusion/exclusion criteria, whose DNT cells show the&#xD;
             most potent killing (minimum &gt;10% killing) of AML patient's blast cells (blast cells&#xD;
             frozen at time of diagnosis or relapse) will be approached for participation in this&#xD;
             study.&#xD;
&#xD;
        Donor Exclusion Criteria:&#xD;
&#xD;
          1. With a history of high risk behavior including, but not limited to, a history of&#xD;
             piercing (except ear lobes), tattoos or other body modification.&#xD;
&#xD;
          2. Has serious illnesses such as cardiovascular disease &amp; cancer.&#xD;
&#xD;
          3. Has sexually transmissible disease.&#xD;
&#xD;
          4. Has history of intravenous drug use.&#xD;
&#xD;
          5. Persons who received any vaccinations in past 3 months prior to enrolment into this&#xD;
             study.&#xD;
&#xD;
          6. Persons who travel outside the U.S. and Canada in the past 3 years prior to enrolment&#xD;
             into this study, to areas that are considered endemic for malaria.&#xD;
&#xD;
          7. Persons who have received blood components or other human tissues in the past 12&#xD;
             months prior to enrolment into this study (however this may be reduced to 6 months if&#xD;
             nucleic acid testing (NAT) is used for the tests).&#xD;
&#xD;
          8. Pregnant or lactating.&#xD;
&#xD;
          9. Persons at risk of transmitting a hematological or immunological disease.&#xD;
&#xD;
         10. Persons with transmissible genetic diseases in the family.&#xD;
&#xD;
         11. On prescription medication.&#xD;
&#xD;
         12. Persons with prion-related disease.&#xD;
&#xD;
         13. Persons with a neurological disease of an unestablished etiology.&#xD;
&#xD;
         14. Persons with active encephalitis or meningitis of infectious or unknown etiology.&#xD;
&#xD;
         15. Persons with rabies or persons who, within the past 6 months, were bitten by an animal&#xD;
             and treated as if the animal was rabid.&#xD;
&#xD;
         16. Persons with a family history of Creutzfeldt-Jakob disease.&#xD;
&#xD;
         17. Persons who have received human-derived pituitary growth hormone or dura mata.&#xD;
&#xD;
         18. Persons who have known or suspected sepsis at the time of donation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Mark Minden, MD</last_name>
    <phone>416-946-2015</phone>
    <email>mark.minden@uhn.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mark Minden</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <last_update_submitted>April 16, 2021</last_update_submitted>
  <last_update_submitted_qc>April 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>allogenic double negative T cells</keyword>
  <keyword>DNT cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</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/NCT03027102
org study id: OZM-079
nct id: NCT03027102
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This study aims to determine the safety and toxicity of incremental doses of Double Negative
      T (DNT) cells in human subjects with high risk acute myeloid leukemia (AML). DNT cells are
      mature T lymphocytes that comprise ~1% of white blood cells in humans. Injection of DNTs from
      healthy donors has been demonstrated to be effective against AML cells. DNT cells will be
      collected from healthy volunteers and injected into patients.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with adverse events and abnormal laboratory studies.
time frame: 2 years
description: Patients will be assessed for adverse events based upon, but not limited to, monitoring of vital signs and prescribed laboratory studies. Adverse events (AE) will use the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE). This study will utilize the CTCAE Version 4.03 for adverse event reporting.
measure: Number of cells with disease specific mutations per patient
time frame: 2 years
description: Quantitive real time polymerase chain reaction (PCR) analysis for disease specific mutations will be performed on the bone marrow aspirate.
measure: Leukemia load
time frame: 2 years
description: Peripheral blood will be obtained after DNT cell infusion to monitor leukemia load and residual disease by determining the frequency of leukemic cell markers on cells using flow cytometry.
arm group label: Patient Arm
arm group type: Experimental
description: Patients will receive DNT cells from healthy donors.
arm group label: Donor Arm
arm group type: No Intervention
description: Healthy volunteer donors will donate blood.
intervention type: Biological
intervention name: DNT cells
description: DNT cells will be expanded (increased in numbers) in the laboratory, in order to enhance their tumour destroying potential before infusion into AML patients.
arm group label: Patient Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Mark Minden, MD
phone: 416-946-2015
email: mark.minden@uhn.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute