<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/NCT03265717</url>
  </required_header>
  <id_info>
    <org_study_id>INVAC1-CT-201</org_study_id>
    <nct_id>NCT03265717</nct_id>
  </id_info>
  <brief_title>DNA Plasmid Encoding a Modified Human Telomerase Reverse Transcriptase (hTERT), Invac-1 in Chronic Lymphocytic Leukemia</brief_title>
  <official_title>A Phase II Study of INVAC-1 as Treatment of Patients With High-risk Chronic Lymphocytic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Invectys</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Invectys</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>
      Phase 2 study to assess the efficacy of INVAC-1, a DNA plasmid encoding a modified human&#xD;
      telomerase reverse transcriptas (hTERT) protein, at a dose of 800 µg for 6 cycles 4 weeks&#xD;
      apart on Minimal Residual Disease (MRD) eradication rate in the bone marrow, either as a&#xD;
      single agent in a high risk &quot;watch and wait&quot; group (group 1 - 42 patients) or in combination&#xD;
      with ibrutinib (group 2 - 42 patients), in patients with Chronic Lymphocytic Leukemia (CLL).&#xD;
&#xD;
      Pharmacodynamics and safety will also be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be a phase II, open label, single-arm trial of INVAC-1 at a dose of 800 µg in&#xD;
      patients with CLL.&#xD;
&#xD;
      The primary goal of the study is to achieve MRD negativity in each group. 42 patients are to&#xD;
      be included in each study group.&#xD;
&#xD;
      Group 1: Untreated high risk &quot;watch and wait&quot; Newly diagnosed patients not eligible for any&#xD;
      approved treatment (using NCI Working Group criteria), but having some poor prognosis&#xD;
      characteristics (defined by MD Anderson Cancer Center nomogram criteria). Patients will be&#xD;
      treated by INVAC-1 for 6 doses at 4-week intervals and then MRD will be assessed. Patients&#xD;
      will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who&#xD;
      become MRD+ during follow-up, INVAC-1 can be resumed for 6 months.&#xD;
&#xD;
      Group 2: Ibrutinib treated patients Patients who are receiving ibrutinib as 1st or 2nd line&#xD;
      treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD.&#xD;
      MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of&#xD;
      the combined treatment period, MRD will be assessed. MRD-negative patients (defined as &lt;0.01%&#xD;
      of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib.&#xD;
      Then, they will be followed-up regularly for two years. Patients who become MRD-positive&#xD;
      after being MRD-negative will resume ibrutinib single agent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    sponsor decision&#xD;
  </why_stopped>
  <start_date type="Actual">July 25, 2018</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 30, 2020</primary_completion_date>
  <phase>Phase 2</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>Minimal Residual Disease (MRD) eradication rate in the bone marrow</measure>
    <time_frame>6 months</time_frame>
    <description>MRD eradication rate (by standardized 4-color flow cytometry, with a limit of detection of 0.01% CLL cells among total leucocytes in the bone marrow after 6 monthly injections of INVAC-1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MRD eradication rate in blood after 6 monthly injections of INVAC-1</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of MRD eradication in bone marrow and blood</measure>
    <time_frame>approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of partial and complete response by IWCLL 2018</measure>
    <time_frame>every 6 months for 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS as assessed by investigators according to IWCLL 2018 criteria</measure>
    <time_frame>approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to next CLL treatment</measure>
    <time_frame>approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>up to 7 months</time_frame>
    <description>type, frequency, severity as graded by NCI CTCAE v.4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cellular (CD4 &amp; CD8) specific anti hTert response by FACS including cytokine polarization Th1, Th2, Th17</measure>
    <time_frame>every 6 months for 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of blood circulating CD4, CD8, Treg, NK cells</measure>
    <time_frame>every 6 months for 3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Leukemia, Lymphocytic, Chronic, B-Cell</condition>
  <arm_group>
    <arm_group_label>Group 1: Untreated high risk &quot;watch and wait&quot;</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Newly diagnosed patients not eligible for any approved treatment (using NCI Working Group criteria), but having some poor prognosis characteristics (defined by MDACC nomogram criteria). Patients will be treated by INVAC-1 for 6 months and then MRD will be assessed. Patients will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who become MRD+ during follow-up, INVAC-1 can be resumed for one year.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: Ibrutinib treated patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who are receiving ibrutinib as 1st or 2nd line treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD. MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of the combined treatment period, MRD will be assessed. MRD-negative patients (defined as &lt;0.01% of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib. Then, they will be followed-up regularly for two years. Patients who become MRD-positive after being MRD-negative will resume ibrutinib single agent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>INVAC-1</intervention_name>
    <description>Patients are treated by INVAC-1 for 6 cycles at 4-week intervals</description>
    <arm_group_label>Group 1: Untreated high risk &quot;watch and wait&quot;</arm_group_label>
    <arm_group_label>Group 2: Ibrutinib treated patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Group 1: Untreated high risk &quot;watch and wait&quot;&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years old&#xD;
&#xD;
          2. Rai stage 0 - II without active disease according to IWCLL 2018 criteria&#xD;
&#xD;
          3. Predicted time to first treatment of ≤3 years according to MDACC nomogram.&#xD;
&#xD;
          4. ECOG performance status of 0-2&#xD;
&#xD;
          5. Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine&#xD;
             transaminase (ALT) &lt; 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x&#xD;
             ULN except Gilbert's Syndrome where a direct bilirubin ≤ 1.5 ULN will be used.&#xD;
&#xD;
          6. Adequate renal function, defined as an estimated creatinine clearance ≥30 mL/min using&#xD;
             the Cockcroft-Gault equation&#xD;
&#xD;
          7. Willingness to receive all outpatient treatment, all laboratory monitoring, and all&#xD;
             radiological evaluations at the institution that administers study drug for the entire&#xD;
             study&#xD;
&#xD;
          8. Willingness of male and female patients, if sexually active, to use an effective&#xD;
             barrier method of contraception during the study and for 3 months following the last&#xD;
             dose of study drug&#xD;
&#xD;
          9. Ability to provide written informed consent and to understand and comply with the&#xD;
             requirements of the study&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Any investigational agent(s) within 4 weeks prior to entry&#xD;
&#xD;
          2. Uncontrolled autoimmune hemolytic anemia (Hgb &lt; 11g/deciliter) or idiopathic&#xD;
             thrombocytopenic purpura (&lt; 100,000/µl)&#xD;
&#xD;
          3. Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies)&#xD;
             intended specifically to treat CLL&#xD;
&#xD;
          4. Treatment with corticosteroids other than physiological replacement within the&#xD;
             previous week or treatment with immunosuppressive medication within the previous week.&#xD;
&#xD;
          5. Major surgery within 4 weeks prior to inclusion&#xD;
&#xD;
          6. Currently active, clinically significant cardiovascular disease or a history of&#xD;
             myocardial infarction within 6 months prior to inclusion&#xD;
&#xD;
          7. Uncontrolled active systemic fungal, bacterial, viral, or other infection or&#xD;
             requirement for intravenous (IV) antibiotics&#xD;
&#xD;
          8. Known history of infection with human immunodeficiency virus (HIV)&#xD;
&#xD;
          9. Serologic status reflecting active hepatitis B or C infection.&#xD;
&#xD;
         10. History of stroke or intracranial hemorrhage within 6 months prior to enrolment&#xD;
&#xD;
         11. Current life-threatening illness, medical condition, or organ-system dysfunction that&#xD;
             could compromise patient safety or put the study at risk&#xD;
&#xD;
         12. Breast-feeding or pregnant women, or patients for whom there is a risk of conception&#xD;
             and who are unable or unwilling to use appropriate contraception (for male and female&#xD;
             patients up to 4 months after end of ibrutinib.)&#xD;
&#xD;
         13. Previous malignancy with life expectancy less than 6 months or requiring systemic&#xD;
             treatment (except colorectal cancer, history of basal cell carcinoma of skin or&#xD;
             pre-invasive carcinoma of the cervix with adequate treatment)&#xD;
&#xD;
         14. Known drug abuse/ alcohol abuse&#xD;
&#xD;
         15. Severe organ failures or diseases, including: clinically relevant coronary disease,&#xD;
             myocardial infarction or any other relevant cardiovascular disorder within 12 months&#xD;
             before study entry, severe psychiatric illness and severe infection.&#xD;
&#xD;
        Group 2: Ibrutinib treated patients&#xD;
&#xD;
        Inclusion Criteria&#xD;
&#xD;
          1. Age ≥ 18 years old&#xD;
&#xD;
          2. Males or females with CLL diagnosed according to IWCLL diagnostic criteria who have&#xD;
             been treated with ibrutinib therapy for at least 12 months and have had no more than 1&#xD;
             other treatment for CLL prior to receiving ibrutinib.&#xD;
&#xD;
          3. Currently in complete or partial remission (PR)/PR with lymphocytosis (PRL)&#xD;
&#xD;
          4. MRD positivity defined as &gt;0.5% CLL cells in the bone marrow by flow cytometry&#xD;
&#xD;
          5. ECOG performance status of 0-2&#xD;
&#xD;
          6. Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine&#xD;
             transaminase (ALT) &lt; 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x&#xD;
             ULN, unless Gilbert's Syndrome where a direct bilirubin ≤ 1.5 ULN will be used.&#xD;
&#xD;
          7. Adequate renal function, defined as estimated creatinine clearance ≥ 30 mL/min using&#xD;
             the Cockcroft-Gault equation&#xD;
&#xD;
          8. Willingness to receive all outpatient treatment, all laboratory monitoring, and all&#xD;
             radiological evaluations at the institution that administers study drug for the entire&#xD;
             study&#xD;
&#xD;
          9. Willingness of male and female patients, if sexually active, to use an effective&#xD;
             barrier method of contraception during the study and for 3 months following the last&#xD;
             dose of study drug&#xD;
&#xD;
         10. Ability to provide written informed consent and to understand and comply with the&#xD;
             requirements of the study&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Any investigational agent(s) within 4 weeks prior to entry&#xD;
&#xD;
          2. Known involvement of the central nervous system by lymphoma or leukemia&#xD;
&#xD;
          3. History or current evidence of Richter's transformation or prolymphocytic leukemia&#xD;
&#xD;
          4. Uncontrolled autoimmune hemolytic anemia (Hgb &lt; 11g/deciliter) or idiopathic&#xD;
             thrombocytopenic purpura (&lt; 100,000/µl)&#xD;
&#xD;
          5. More than one previous treatment by chemotherapy or patients who previously received&#xD;
             alemtuzumab intended specifically to treat CLL&#xD;
&#xD;
          6. Corticosteroid use within 1 week prior to first dose of study drug, with the exception&#xD;
             of inhaled, topical, or other local administrations. Patients requiring systemic&#xD;
             steroids at daily doses &gt; 20 mg prednisone (or corticosteroid equivalent), or those&#xD;
             who are administered steroids for leukemia control or white blood cell&#xD;
             (WBC)-count-lowering are excluded&#xD;
&#xD;
          7. Major surgery within 4 weeks prior to inclusion&#xD;
&#xD;
          8. Currently active, clinically significant cardiovascular disease or a history of&#xD;
             myocardial infarction within 6 months prior to inclusion&#xD;
&#xD;
          9. Uncontrolled active systemic fungal, bacterial, viral, or other infection or&#xD;
             requirement for intravenous (IV) antibiotics&#xD;
&#xD;
         10. Known history of infection with human immunodeficiency virus (HIV)&#xD;
&#xD;
         11. Serologic status reflecting active hepatitis B or C infection&#xD;
&#xD;
         12. History of stroke or intracranial hemorrhage within 6 months prior to enrollment&#xD;
&#xD;
         13. Current life-threatening illness, medical condition, or organ-system dysfunction that&#xD;
             could compromise patient safety or put the study at risk&#xD;
&#xD;
         14. Requirement for anticoagulation with warfarin, or for treatment with a strong CYP3A4/5&#xD;
             and/or CYP2D6 inhibitor&#xD;
&#xD;
         15. Breast-feeding or pregnant women, or patients for whom there is a risk of conception&#xD;
             and who are unable or unwilling to use appropriate contraception (for male and female&#xD;
             patients up to 4 months after end of ibrutinib.)&#xD;
&#xD;
         16. Previous malignancy with life expectancy less than 6 months or requiring systemic&#xD;
             treatment (except colorectal cancer, history of basal cell or squamous carcinoma of&#xD;
             skin or pre-invasive carcinoma of the cervix with adequate treatment)&#xD;
&#xD;
         17. Known drug abuse/ alcohol abuse&#xD;
&#xD;
         18. Severe organ failures or diseases, including: clinically relevant coronary disease,&#xD;
             myocardial infarction or any other relevant cardiovascular disorder within 12 months&#xD;
             before study entry, severe psychiatric illness and severe infection.&#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>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>July 6, 2020</last_update_submitted>
  <last_update_submitted_qc>July 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>telomerase, tert, cancer vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
  </condition_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/NCT03265717
org study id: INVAC1-CT-201
nct id: NCT03265717
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase 2 study to assess the efficacy of INVAC-1, a DNA plasmid encoding a modified human
      telomerase reverse transcriptas (hTERT) protein, at a dose of 800 µg for 6 cycles 4 weeks
      apart on Minimal Residual Disease (MRD) eradication rate in the bone marrow, either as a
      single agent in a high risk "watch and wait" group (group 1 - 42 patients) or in combination
      with ibrutinib (group 2 - 42 patients), in patients with Chronic Lymphocytic Leukemia (CLL).

      Pharmacodynamics and safety will also be assessed.
The study will be a phase II, open label, single-arm trial of INVAC-1 at a dose of 800 µg in
      patients with CLL.

      The primary goal of the study is to achieve MRD negativity in each group. 42 patients are to
      be included in each study group.

      Group 1: Untreated high risk "watch and wait" Newly diagnosed patients not eligible for any
      approved treatment (using NCI Working Group criteria), but having some poor prognosis
      characteristics (defined by MD Anderson Cancer Center nomogram criteria). Patients will be
      treated by INVAC-1 for 6 doses at 4-week intervals and then MRD will be assessed. Patients
      will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who
      become MRD+ during follow-up, INVAC-1 can be resumed for 6 months.

      Group 2: Ibrutinib treated patients Patients who are receiving ibrutinib as 1st or 2nd line
      treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD.
      MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of
      the combined treatment period, MRD will be assessed. MRD-negative patients (defined as <0.01%
      of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib.
      Then, they will be followed-up regularly for two years. Patients who become MRD-positive
      after being MRD-negative will resume ibrutinib single agent.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Minimal Residual Disease (MRD) eradication rate in the bone marrow
time frame: 6 months
description: MRD eradication rate (by standardized 4-color flow cytometry, with a limit of detection of 0.01% CLL cells among total leucocytes in the bone marrow after 6 monthly injections of INVAC-1
measure: MRD eradication rate in blood after 6 monthly injections of INVAC-1
time frame: 6 months
measure: Duration of MRD eradication in bone marrow and blood
time frame: approximately 3 years
measure: Cumulative incidence of partial and complete response by IWCLL 2018
time frame: every 6 months for 3 years
measure: PFS as assessed by investigators according to IWCLL 2018 criteria
time frame: approximately 3 years
measure: Time to next CLL treatment
time frame: approximately 3 years
measure: Overall survival
time frame: approximately 3 years
measure: Adverse events
time frame: up to 7 months
description: type, frequency, severity as graded by NCI CTCAE v.4.03
measure: Cellular (CD4 & CD8) specific anti hTert response by FACS including cytokine polarization Th1, Th2, Th17
time frame: every 6 months for 3 years
measure: Count of blood circulating CD4, CD8, Treg, NK cells
time frame: every 6 months for 3 years
arm group label: Group 1: Untreated high risk "watch and wait"
arm group type: Experimental
description: Newly diagnosed patients not eligible for any approved treatment (using NCI Working Group criteria), but having some poor prognosis characteristics (defined by MDACC nomogram criteria). Patients will be treated by INVAC-1 for 6 months and then MRD will be assessed. Patients will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who become MRD+ during follow-up, INVAC-1 can be resumed for one year.
arm group label: Group 2: Ibrutinib treated patients
arm group type: Experimental
description: Patients who are receiving ibrutinib as 1st or 2nd line treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD. MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of the combined treatment period, MRD will be assessed. MRD-negative patients (defined as <0.01% of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib. Then, they will be followed-up regularly for two years. Patients who become MRD-positive after being MRD-negative will resume ibrutinib single agent.
intervention type: Biological
intervention name: INVAC-1
description: Patients are treated by INVAC-1 for 6 cycles at 4-week intervals
arm group label: Group 1: Untreated high risk "watch and wait"
arm group label: Group 2: Ibrutinib treated patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
sharing ipd: Undecided