<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/NCT02203825</url>
  </required_header>
  <id_info>
    <org_study_id>CM-14-001</org_study_id>
    <secondary_id>5R44HL099217-03</secondary_id>
    <nct_id>NCT02203825</nct_id>
  </id_info>
  <brief_title>Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands</brief_title>
  <official_title>A Phase 1 Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands in Patients With Acute Myeloid Leukemia (AML)/Advanced Myelodysplastic Syndrome (MDS-RAEB) and Multiple Myeloma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celyad Oncology SA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Celyad Oncology SA</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase I clinical trial is evaluating chimeric-antigen receptor (CAR) T-cells (CM-CS1 T&#xD;
      cells) which recognize NKG2D-ligands on the surface of cancer cells. This study evaluates the&#xD;
      safety and feasibility of administering a single intravenous dose of CM-CS1 CAR T-cells to&#xD;
      patients with AML, MDS-RAEB and Multiple Myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a study for patients with AML or MDS-RAEB that is not in remission and for which&#xD;
      there are no reasonable standard treatment options and for patients with relapsed/refractory&#xD;
      multiple myeloma with progressive disease.&#xD;
&#xD;
      In this study, the participant's white blood cells (T-cells) will be collected and modified&#xD;
      such that the T-cells are able to recognize specific molecules (called NKG2D-ligands), that&#xD;
      are expressed on the surface of cancer cells in these diseases. This modification is a&#xD;
      genetic change to the T-cells. The modified T cells, called CM-CS1 T-cells, are then given&#xD;
      back to the participant by a single intravenous infusion. In this study, participants will&#xD;
      not receive any chemotherapy prior to infusion of the CM-CS1 T-cells.&#xD;
&#xD;
      The study will evaluate whether it is safe and feasible to administer CM-CS1 T-cells to&#xD;
      participants with AML/MDS-RAEB and multiple myeloma. It will also evaluate whether the CM-CS1&#xD;
      T-cells have a beneficial effect against the cancer cells. Another goal of the study is to&#xD;
      learn more about the persistence and function of the CM-CS1 T-cells in the body.&#xD;
&#xD;
      Participants will be followed very closely during the first month after infusion. They are&#xD;
      required to remain within 50 miles of Brigham and Women's Hospital (Boston, MA) for 10 days&#xD;
      after the infusion and will be followed three times per week for the first 21 days and at day&#xD;
      28. Subsequently, participants will be followed monthly until 6 months after infusion, every&#xD;
      3 months until 15 months after infusion and at 24 months after infusion. Because this study&#xD;
      involves gene transfer, participants will be followed yearly for up to 15 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">March 2018</completion_date>
  <primary_completion_date type="Actual">March 2018</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>Safety and feasibility of intravenous administration of CM-CS1 T-cells.</measure>
    <time_frame>24 months</time_frame>
    <description>Safety will be defined by the occurence of study-related serious and non-serious adverse events.&#xD;
Feasibility will be defined by the frequency of subjects enrolled who do not receive CM-CS1 T-cells.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical and biologic responses</measure>
    <time_frame>24 months</time_frame>
    <description>Clinical anti-tumor effect by standard criteria Progression-Free survival Persistence and function of CM-CS1 T-cells</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>CM-CS1 T-cell infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The treatment will consist of a single infusion of CM-CS1 cells.&#xD;
The following dose levels will be evaluated:&#xD;
Cohort 1: 1x 10^6 CM-CS1 T-cells Cohort 2: 3x 10^6 CM-CS1 T-cells Cohort 3: 1x 10^7 CM-CS1 T-cells Cohort 4: 3x 10^7 CM-CS1 T-cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CM-CS1 T-cell infusion</intervention_name>
    <description>Each patient will receive a single dose of CM-CS1 T-cells by intravenous infusion.</description>
    <arm_group_label>CM-CS1 T-cell infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        General eligibility criteria:&#xD;
&#xD;
          -  ECOG performance status 0 or 1.Patients with multiple myeloma who have an ECOG&#xD;
             performance status of 2 based on peripheral neuropathy from prior therapies are&#xD;
             eligible.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
          -  Pathological confirmation of AML, MDS-RAEB or Multiple myeloma.&#xD;
&#xD;
          -  Agree to use adequate contraception prior to the study, for the duration of study&#xD;
             participation, and 4 months after completion of CM-CS1 CART-cell administration.&#xD;
&#xD;
          -  Ability to adhere with the study visit schedule and other protocol procedures.&#xD;
&#xD;
          -  Willingness to remain within a 50 mile radius of Brigham Women's Hospital during the&#xD;
             initial 10 days following CM-CS1 infusion&#xD;
&#xD;
        Disease specific eligibility criteria for patients with AML, MDS-RAEB:&#xD;
&#xD;
          -  Pathological confirmation of AML, MDS-RAEB according to WHO classification (CMML is&#xD;
             excluded) that is not in remission (defined as &gt;5% blasts in bone marrow or peripheral&#xD;
             blood) and for which there are no reasonable standard treatment options.&#xD;
&#xD;
          -  No known or suspected CNS disease. A neurologic exam is required and signs or symptoms&#xD;
             suggestive of potential CNS disease require CNS imaging.&#xD;
&#xD;
          -  Disease status deemed not to require additional therapy for at least 4 weeks from&#xD;
             enrollment.&#xD;
&#xD;
          -  Life expectancy of greater than 4 weeks.&#xD;
&#xD;
          -  Participants must have satisfactory organ function as defined below:&#xD;
&#xD;
               1. Total bilirubin ≤2.0 × institutional upper limit of normal (Except for subjects&#xD;
                  with known Gilbert's syndrome)&#xD;
&#xD;
               2. AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal&#xD;
&#xD;
               3. Creatinine ≤ 2.0 mg/dL&#xD;
&#xD;
        Disease specific eligibility criteria for patients with multiple myeloma:&#xD;
&#xD;
          -  Diagnosis of active multiple myeloma according to the International Myeloma Working&#xD;
             Group diagnostic criteria.&#xD;
&#xD;
          -  Relapsed or relapsed/refractory multiple myeloma with progressive disease&#xD;
&#xD;
          -  Presence of measurable disease as defined as one or more of the following:&#xD;
&#xD;
               1. Serum M-protein &gt;0.5g/dl&#xD;
&#xD;
               2. Urine M-protein &gt; 200mg/24hr&#xD;
&#xD;
               3. Serum FLC assay: involved FLC level &gt; 10mg/dl with abnormal serum FLC ratio&#xD;
&#xD;
               4. Measurable plasmocytoma in non-secretory patients.&#xD;
&#xD;
          -  Previous treatment with both an immunomodulator and a proteosome inhibitor therapy&#xD;
&#xD;
          -  Life expectancy of greater than 12 weeks&#xD;
&#xD;
          -  No known or suspected CNS involvement. A neurologic exam is required and signs or&#xD;
             symptoms of potential CNS involvement require CNS imaging. Peripheral neuropathy is&#xD;
             acceptable.&#xD;
&#xD;
          -  Participants must have satisfactory organ and marrow function as defined below:&#xD;
&#xD;
               1. Absolute neutrophil count &gt; 500/mcL. Screening ANC should be independent of G-CSF&#xD;
                  and GM-CSF support for at least 1 week and of pegylated G-CSF for at least 2&#xD;
                  weeks&#xD;
&#xD;
               2. Platelets &gt;20,000/mcL. Subjects may receive platelet transfusions, if clinically&#xD;
                  indicated, in accordance with institutional guidelines.&#xD;
&#xD;
               3. Total bilirubin ≤2.0 × institutional upper limit of normal. (Except patients with&#xD;
                  known Gilbert's syndrome)&#xD;
&#xD;
               4. AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal&#xD;
&#xD;
               5. Creatinine ≤ 2.0 mg/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who have received chemotherapy or radiotherapy within 3 weeks prior to&#xD;
             entering the study or those who have not recovered from adverse events due to agents&#xD;
             administered more than 3 weeks earlier.&#xD;
&#xD;
          -  Concurrent systemic steroid or other immunosuppressive therapy.&#xD;
&#xD;
          -  Participants who are concurrently receiving any other investigational agents, or have&#xD;
             received another investigational agent within 3 weeks before enrollment.&#xD;
&#xD;
          -  Participants who have received prior allogeneic stem cell transplantation, gene&#xD;
             therapy, or adoptive T-cell therapy.&#xD;
&#xD;
          -  Active infections necessitating use of treatment antibiotics/antivirals during the&#xD;
             screening period (prophylaxis is acceptable) or evidence of an active communicable&#xD;
             infectious disease.&#xD;
&#xD;
          -  Participants who underwent major surgery within 4 weeks before day 0 of planned CM-CS1&#xD;
             T-cell infusion (this does not include placement of vascular access device or tumor&#xD;
             biopsies).&#xD;
&#xD;
          -  Participants with any known history of primary immunodeficiency.&#xD;
&#xD;
          -  History of allergic reactions or hypersensitivity attributed to Human serum albumin or&#xD;
             Plasma-lyte A.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness or serious uncontrolled medical disorder&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Known HIV-positive participants are ineligible because the effect of transducing&#xD;
             HIV-infected lymphocytes with the chimeric NKG2D- transgene on the disease course is&#xD;
             unknown.&#xD;
&#xD;
          -  Clinically relevant active infection including active hepatitis B or C or any other&#xD;
             concurrent disease which in the judgment of the Investigator would make the subject&#xD;
             inappropriate for enrollment on this study.&#xD;
&#xD;
          -  Active autoimmune disease&#xD;
&#xD;
          -  History of a malignancy other than one of the malignancies in this study with&#xD;
             exception of the following circumstances:&#xD;
&#xD;
               1. Patients with a history of malignancy who have been adequately treated and have&#xD;
                  been disease-free for at least 2 years are not excluded.&#xD;
&#xD;
               2. Patients with adequately treated active non-invasive cancers (such as&#xD;
                  non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers) are&#xD;
                  not excluded.&#xD;
&#xD;
          -  Unwillingness to use an effective contraceptive method during the study and at least 4&#xD;
             months after administration of CM-CS1 T-cells unless subject is naturally infertile.&#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>Sarah Nikiforow, MD; PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.celyad.com</url>
    <description>Sponsor</description>
  </link>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>May 30, 2018</last_update_submitted>
  <last_update_submitted_qc>May 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute Myeloid Leukemia</keyword>
  <keyword>NKG2D</keyword>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Cell Therapy</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>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</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/NCT02203825
org study id: CM-14-001
secondary id: 5R44HL099217-03
nct id: NCT02203825
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This Phase I clinical trial is evaluating chimeric-antigen receptor (CAR) T-cells (CM-CS1 T
      cells) which recognize NKG2D-ligands on the surface of cancer cells. This study evaluates the
      safety and feasibility of administering a single intravenous dose of CM-CS1 CAR T-cells to
      patients with AML, MDS-RAEB and Multiple Myeloma.
This is a study for patients with AML or MDS-RAEB that is not in remission and for which
      there are no reasonable standard treatment options and for patients with relapsed/refractory
      multiple myeloma with progressive disease.

      In this study, the participant's white blood cells (T-cells) will be collected and modified
      such that the T-cells are able to recognize specific molecules (called NKG2D-ligands), that
      are expressed on the surface of cancer cells in these diseases. This modification is a
      genetic change to the T-cells. The modified T cells, called CM-CS1 T-cells, are then given
      back to the participant by a single intravenous infusion. In this study, participants will
      not receive any chemotherapy prior to infusion of the CM-CS1 T-cells.

      The study will evaluate whether it is safe and feasible to administer CM-CS1 T-cells to
      participants with AML/MDS-RAEB and multiple myeloma. It will also evaluate whether the CM-CS1
      T-cells have a beneficial effect against the cancer cells. Another goal of the study is to
      learn more about the persistence and function of the CM-CS1 T-cells in the body.

      Participants will be followed very closely during the first month after infusion. They are
      required to remain within 50 miles of Brigham and Women's Hospital (Boston, MA) for 10 days
      after the infusion and will be followed three times per week for the first 21 days and at day
      28. Subsequently, participants will be followed monthly until 6 months after infusion, every
      3 months until 15 months after infusion and at 24 months after infusion. Because this study
      involves gene transfer, participants will be followed yearly for up to 15 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and feasibility of intravenous administration of CM-CS1 T-cells.
time frame: 24 months
description: Safety will be defined by the occurence of study-related serious and non-serious adverse events.
Feasibility will be defined by the frequency of subjects enrolled who do not receive CM-CS1 T-cells.
measure: Clinical and biologic responses
time frame: 24 months
description: Clinical anti-tumor effect by standard criteria Progression-Free survival Persistence and function of CM-CS1 T-cells
arm group label: CM-CS1 T-cell infusion
arm group type: Experimental
description: The treatment will consist of a single infusion of CM-CS1 cells.
The following dose levels will be evaluated:
Cohort 1: 1x 10^6 CM-CS1 T-cells Cohort 2: 3x 10^6 CM-CS1 T-cells Cohort 3: 1x 10^7 CM-CS1 T-cells Cohort 4: 3x 10^7 CM-CS1 T-cells
intervention type: Biological
intervention name: CM-CS1 T-cell infusion
description: Each patient will receive a single dose of CM-CS1 T-cells by intravenous infusion.
arm group label: CM-CS1 T-cell infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sarah Nikiforow, MD; PhD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
country: United States
url: http://www.celyad.com
description: Sponsor
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes