<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/NCT03790072</url>
  </required_header>
  <id_info>
    <org_study_id>TCB-202-001</org_study_id>
    <secondary_id>2018-000409-22</secondary_id>
    <nct_id>NCT03790072</nct_id>
  </id_info>
  <brief_title>Ex-vivo Expanded γδ T-lymphocytes (OmnImmune®) in Patients With Acute Myeloid Leukaemia (AML)</brief_title>
  <official_title>Safety and Efficacy of Ex-vivo Expanded Allogeneic γδ T-lymphocytes (OmnImmune®) in Patients With Active Relapsed or Refractory Acute Myeloid Leukaemia (AML) Who Are Not Eligible for or do Not Consent to High Dose Salvage Chemotherapy and/or Allogeneic Haematopoietic Cell Transplantation (HCT). A Dose Escalation, Open-label, Phase I Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TC Biopharm</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TC Biopharm</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <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 investigates the potential curative properties of gamma delta T-cells obtained&#xD;
      from a blood-related donor of an AML patient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, safety and efficacy, escalating dose, single arm study on 9 adult&#xD;
      subjects (3 cohorts) and 3+3 design will be used. HLA typed patients and potential&#xD;
      blood-related donors will be screened for comorbidities. Suitably matched or haploidentical&#xD;
      family donors will be selected according to protocol specified criteria and institutional&#xD;
      guidelines of participating site.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 27, 2018</start_date>
  <completion_date type="Actual">March 26, 2021</completion_date>
  <primary_completion_date type="Actual">March 26, 2021</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Dose escalation, 3 cohorts, x10 dose increments between cohorts (10^6, 10^7, 10^8 of cells per kg of body weight).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events (AEs) [Safety]</measure>
    <time_frame>Day 28 after completion of treatment</time_frame>
    <description>Safety of OmnImmune® assessed by incidence of treatment-emergent adverse events (AEs) per patient graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Dose-Limiting Toxicities (DLTs) [Tolerability]</measure>
    <time_frame>Day 28 after completion of treatment</time_frame>
    <description>Tolerability of OmnImmune® assessed by incidence of dose-limiting toxicities (DLTs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients reaching Complete Remission (CR) [Efficacy]</measure>
    <time_frame>24 months post-treatment</time_frame>
    <description>Efficacy of OmnImmune® assessed by number of patients reaching Complete Remission (CR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) [Efficacy]</measure>
    <time_frame>24 months post-treatment</time_frame>
    <description>Efficacy of OmnImmune® assessed by overall survival (OS) measured in months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (QoL)</measure>
    <time_frame>24 months post-treatment</time_frame>
    <description>Quality of life determined by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 'C30' which comprises 30 items (i.e. single questions), 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Persistence of γδ T cells</measure>
    <time_frame>Before treatment and up to 24 months after treatment</time_frame>
    <description>Persistence of γδ T cells assessed by number and phenotype of γδ T cells using flow cytometry assay in peripheral blood and bone marrow from dosed patients</description>
  </other_outcome>
  <other_outcome>
    <measure>Phenotype of γδ T cells</measure>
    <time_frame>Before treatment and up to 24 months after treatment</time_frame>
    <description>Phenotype of γδ T cells assessed by flow cytometry assay in peripheral blood and bone marrow from dosed patients</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After inclusion, patients will receive conditioning chemotherapy consisting of non-investigational medicinal products (non-IMPs): fludarabine 25 mg/m2 from day -6 until day -2 (inclusive) and cyclophosphamide 500 mg/m2 on days -6 and -5.&#xD;
Subsequently, patients in will be dosed with investigational medicinal product (IMP) OmnImmune® on day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>OmnImmune®</intervention_name>
    <description>infusion of OmnImmune® (expanded gamma delta T lymphocytes)</description>
    <arm_group_label>Treatment Arm</arm_group_label>
    <other_name>fludarabine</other_name>
    <other_name>cyclophosphamide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. History of acute myeloid leukaemia (initially diagnosed by presence of 20% or more&#xD;
             blast cells with myeloid or monocytic differentiation confirmed by flow cytometry in&#xD;
             peripheral blood or bone marrow)&#xD;
&#xD;
          2. Relapsed or refractory AML&#xD;
&#xD;
               1. AML relapse after intensive chemotherapy OR&#xD;
&#xD;
               2. AML relapse after allogeneic HCT OR&#xD;
&#xD;
               3. AML progression on low intensity therapy (low dose cytarabine, 5-azacytidine or&#xD;
                  decitabine) OR&#xD;
&#xD;
               4. No response to at least 4 cycles of low intensity therapy&#xD;
&#xD;
               5. AML refractory to 2 cycles of induction chemotherapy&#xD;
&#xD;
          3. Presence of &gt; 5% of blasts in bone marrow or peripheral blood smear&#xD;
&#xD;
          4. Patient not eligible for or does not consent to high dose salvage chemotherapy and/or&#xD;
             allogeneic Haematopoietic Cell Transplantation (HCT)&#xD;
&#xD;
          5. Considered suitable for lymphodepleting chemotherapy&#xD;
&#xD;
          6. Age 18 years up to the age of 70 (≤ 70)&#xD;
&#xD;
          7. Life expectancy of at least 3 months&#xD;
&#xD;
          8. Karnofsky performance status ≥ 50%&#xD;
&#xD;
          9. Available related HLA-haploidentical or HLA-matched donor&#xD;
&#xD;
         10. Ability to be off systemic prednisone and other immunosuppressive drugs for at least 3&#xD;
             days prior to γδ T cells product infusion. Maintenance replacement steroid is allowed.&#xD;
&#xD;
         11. Patient able to understand and sign written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Uncontrolled infections&#xD;
&#xD;
          2. Renal insufficiency: creatinine &gt; 180 μmol/L or on dialysis&#xD;
&#xD;
          3. Heart failure: EF &lt; 40%&#xD;
&#xD;
          4. Respiratory insufficiency: oxygen therapy required at inclusion in the study&#xD;
&#xD;
          5. Significant liver impairment: bilirubin &gt; 50 μmol/L, AST or ALT &gt; 4 times normal upper&#xD;
             limit&#xD;
&#xD;
          6. Treatment with bisphosphonates (2 months before start)&#xD;
&#xD;
          7. Active autoimmune disease or GvHD&#xD;
&#xD;
          8. Pregnant or breastfeeding&#xD;
&#xD;
          9. Patient of fertile age not using two-barrier method of birth control.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UHKT (Ustav hematologie a krevni transfuze)</name>
      <address>
        <city>Praha</city>
        <zip>128 20</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 31, 2018</study_first_posted>
  <last_update_submitted>March 29, 2021</last_update_submitted>
  <last_update_submitted_qc>March 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gamma Delta T Lymphocytes</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03790072
org study id: TCB-202-001
secondary id: 2018-000409-22
nct id: NCT03790072
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study investigates the potential curative properties of gamma delta T-cells obtained
      from a blood-related donor of an AML patient.
This is an open-label, safety and efficacy, escalating dose, single arm study on 9 adult
      subjects (3 cohorts) and 3+3 design will be used. HLA typed patients and potential
      blood-related donors will be screened for comorbidities. Suitably matched or haploidentical
      family donors will be selected according to protocol specified criteria and institutional
      guidelines of participating site.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Dose escalation, 3 cohorts, x10 dose increments between cohorts (10^6, 10^7, 10^8 of cells per kg of body weight).
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events (AEs) [Safety]
time frame: Day 28 after completion of treatment
description: Safety of OmnImmune® assessed by incidence of treatment-emergent adverse events (AEs) per patient graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
measure: Incidence of Dose-Limiting Toxicities (DLTs) [Tolerability]
time frame: Day 28 after completion of treatment
description: Tolerability of OmnImmune® assessed by incidence of dose-limiting toxicities (DLTs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
measure: Number of patients reaching Complete Remission (CR) [Efficacy]
time frame: 24 months post-treatment
description: Efficacy of OmnImmune® assessed by number of patients reaching Complete Remission (CR)
measure: Overall Survival (OS) [Efficacy]
time frame: 24 months post-treatment
description: Efficacy of OmnImmune® assessed by overall survival (OS) measured in months
measure: Quality of Life (QoL)
time frame: 24 months post-treatment
description: Quality of life determined by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 'C30' which comprises 30 items (i.e. single questions), 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
measure: Persistence of γδ T cells
time frame: Before treatment and up to 24 months after treatment
description: Persistence of γδ T cells assessed by number and phenotype of γδ T cells using flow cytometry assay in peripheral blood and bone marrow from dosed patients
measure: Phenotype of γδ T cells
time frame: Before treatment and up to 24 months after treatment
description: Phenotype of γδ T cells assessed by flow cytometry assay in peripheral blood and bone marrow from dosed patients
arm group label: Treatment Arm
arm group type: Experimental
description: After inclusion, patients will receive conditioning chemotherapy consisting of non-investigational medicinal products (non-IMPs): fludarabine 25 mg/m2 from day -6 until day -2 (inclusive) and cyclophosphamide 500 mg/m2 on days -6 and -5.
Subsequently, patients in will be dosed with investigational medicinal product (IMP) OmnImmune® on day 0.
intervention type: Biological
intervention name: OmnImmune®
description: infusion of OmnImmune® (expanded gamma delta T lymphocytes)
arm group label: Treatment Arm
other name: fludarabine
other name: cyclophosphamide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: Czechia
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Cyclophosphamide
mesh term: Fludarabine
sharing ipd: Undecided