<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/NCT01716364</url>
  </required_header>
  <id_info>
    <org_study_id>LeYPh1</org_study_id>
    <nct_id>NCT01716364</nct_id>
  </id_info>
  <brief_title>Safety Study of Anti LewisY Chimeric Antigen Receptor in Myeloma, Acute Myeloid Leukemia or Myelodysplastic Syndrome</brief_title>
  <official_title>A Phase I Study Investigating Safety Immunological Effects of Peripheral Blood T Lymphocytes Transduced With Anti LewisY Chimeric Receptor Gene in LewisY Positive Myeloma, Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter MacCallum Cancer Centre, Australia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peter MacCallum Cancer Centre, Australia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with some forms of acute myeloid leukemia (AML) and multiple myeloma (MM) are not&#xD;
      cured with conventional therapy and new approaches are needed. For the last 15 years we have&#xD;
      investigated the potential of using a patient's own T cells (a type of white blood cell&#xD;
      [WBC]) to eradicate the tumor. We have demonstrated the feasibility of this approach in cell&#xD;
      culture and animal models of AML and MM. Over the last 5 years we have been preparing to&#xD;
      treat patients as part of a Phase I (first in human) clinical trial.&#xD;
&#xD;
      The trial treatment involves collecting the patient's own WBCs from the blood by a standard&#xD;
      well established and safe process called apheresis. The cells are then cultured in a&#xD;
      specialized laboratory (under Good Manufacturing Practice conditions, similar to standards&#xD;
      under which pharmaceuticals are produced) over 12 days to convert the cells to specialized&#xD;
      tumor-attacking T cells. Early in that culture process the cells are exposed to a virus (that&#xD;
      is modified so that it cannot infect or replicate outside the special culture conditions)&#xD;
      that contains a special gene. Via the virus, this gene inserts into the patient's T cells in&#xD;
      culture and gets incorporated into the T cell's genetic machinery. As the T cells replicate,&#xD;
      the new gene produces a protein receptor that becomes part of the patient's T cells. This&#xD;
      protein receptor on the T cells has the capacity to specifically recognize and bind to a&#xD;
      protein on the leukemia or myeloma cells called the &quot;Lewis Y&quot; antigen.&#xD;
&#xD;
      After the modified T cells are infused into the patient, they home into the bone marrow (this&#xD;
      tracking is monitored by special radiological techniques) where the new protein receptor on&#xD;
      the T cell surface can recognize and bind to the cancer cells (which express Lewis Y). Once&#xD;
      bound onto the cancer cells, the T cells get activated and subsequently replicate and kill&#xD;
      the cancer cells. The novelty of this approach is that the T-cells will only kill cells that&#xD;
      have the Lewis Y on their surface - the cancer cells. Moreover, because there are few normal&#xD;
      cells in a person's body that carry Lewis Y, this treatment is likely to only have minor side&#xD;
      effects.&#xD;
&#xD;
      This gene therapy trial is unique and although the primary purpose is to test the safety of&#xD;
      this approach, patients will be monitored closely for anti-tumor responses. As the trial&#xD;
      progresses, the dose of T cells infused will increase, in the hope that this will result in a&#xD;
      better and stronger immune response to the leukemia or myeloma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>January 2010</start_date>
  <completion_date type="Anticipated">December 2013</completion_date>
  <primary_completion_date type="Anticipated">December 2013</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>Number of participants with adverse events.</measure>
    <time_frame>Up to 3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of infused labelled cells localizing in bone marrow</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of infused labelled cells localizing in soft tissue or plasmacytoma.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence or absence of anti-LeY positive T-cells in peripheral blood and bone marrow.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of anti LeY positive T-cells in peripheral blood and bone marrow.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum IFN-γ and IL-2 levels.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence or absence of autoimmune disease.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Location of labelled re-infused T-cells</measure>
    <time_frame>Up to 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LewisY expression assessed with Flow Cytometry in Peripheral Blood and Bone Marrow.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LewisY expression assessed with Flow Cytometry in Peripheral Blood and Bone</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">6</enrollment>
  <condition>Multiple Myeloma</condition>
  <condition>Acute Myeloid Leukaemia</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <arm_group>
    <arm_group_label>Anti-LeY- scFv-CD28-ζ vector.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anti-LeY- scFv-CD28-ζ vector, a non-pathogenic, replication-incompetent retroviral vector specifically designed for this study and produced by EUFETS under GMP-conditions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Anti-LeY- scFv-CD28-ζ vector,.</intervention_name>
    <arm_group_label>Anti-LeY- scFv-CD28-ζ vector.</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Applicable to all Patients&#xD;
&#xD;
          -  Patient is able to undergo apheresis of peripheral blood mononuclear cells (PBMC)&#xD;
             within eight weeks following registration.&#xD;
&#xD;
          -  White cell count (WCC) &lt;30/nL as higher WCC could interfere with the apheresis of&#xD;
             PBMC.&#xD;
&#xD;
          -  Patient has an ECOG performance status of 0 - 1.&#xD;
&#xD;
          -  Patient is deemed capable of undergoing the planned study procedures&#xD;
&#xD;
          -  Patient has adequate organ function:&#xD;
&#xD;
               -  bilirubin &lt;1.5x upper limit of normal (ULN), AST/ALT ≤2.5 x ULN except in&#xD;
                  patients with Gilbert's syndrome&#xD;
&#xD;
               -  Serum Creatinine &lt; 1.5 ×ULN or creatinine clearance &gt; 50ml/min&#xD;
&#xD;
               -  Amylase, lipase ≤1.5xULN&#xD;
&#xD;
          -  Lymphocyte count of ≥0.5x109/L&#xD;
&#xD;
          -  &gt; 18 years of age.&#xD;
&#xD;
          -  Patient has provided written informed consent.&#xD;
&#xD;
          -  No chemotherapy or treatment with G-CSF within 4 weeks prior to the planned apheresis.&#xD;
&#xD;
          -  Applicable to patients with multiple myeloma&#xD;
&#xD;
          -  Patient has histologically or cytologically confirmed diagnosis of multiple myeloma&#xD;
             plus one or more of the criteria set out below must apply:&#xD;
&#xD;
          -  Presence of the following features that are known to be associated with an adverse&#xD;
             prognosis with conventional chemotherapy, high-dose chemotherapy and autologous stem&#xD;
             cell transplant (AUSCT):&#xD;
&#xD;
        Chromosomal abnormalities:&#xD;
&#xD;
          -  13q deletion&#xD;
&#xD;
          -  17p deletion as p53-deletion by IHC on the bm trephine&#xD;
&#xD;
          -  Translocation (4:14)&#xD;
&#xD;
          -  Translocation (14:16)&#xD;
&#xD;
        Clinical features:&#xD;
&#xD;
          -  Progressive disease within 12 months after previous AUSCT&#xD;
&#xD;
          -  Plasmablastic morphology&#xD;
&#xD;
          -  Plasma cell leukaemia&#xD;
&#xD;
               -  Patient planned for high-dose melphalan chemotherapy with AUSCT having had at&#xD;
                  least two prior treatment regimens (which can include prior high-dose&#xD;
                  chemotherapy and AUSCT and must include at least one of thalidomide, lenalidomide&#xD;
                  or bortezomib).&#xD;
&#xD;
               -  Patient has previously proven LewisY expression on the plasma cells prior to&#xD;
                  study entry in an analysis as defined in study criteria&#xD;
&#xD;
               -  Patient is planned to receive high dose melphalan and autograft (after apheresis&#xD;
                  of PBMC)&#xD;
&#xD;
               -  Additional inclusion Criteria applied to patients with acute myeloid leukaemia&#xD;
                  (AML)/high-risk myelodysplastic syndrome (MDS)&#xD;
&#xD;
        All of the following must apply:&#xD;
&#xD;
          -  Patient must either have newly diagnosed AML/high-risk MDS with a poor prognosis or&#xD;
             relapsed/refractory AML/high-risk MDS&#xD;
&#xD;
          -  Patient has previously proven LewisY expression on the myeloblasts prior to study&#xD;
             entry in an analysis as defined in study criteria&#xD;
&#xD;
          -  Patient is planned to receive fludarabine containing regime (FCR) chemotherapy (after&#xD;
             apheresis of PBMC) which is planned to be the last cycle of FCR chemotherapy, no&#xD;
             further FCR chemotherapy should be planned within 3 months after this cycle of FCR&#xD;
&#xD;
        Definition of poor prognosis in AML/high-risk MDS&#xD;
&#xD;
        A patient with AML has a poor prognosis if any of the following is satisfied:&#xD;
&#xD;
          -  Age &gt; 65 years&#xD;
&#xD;
          -  Age 56 - 65 years with any of the following single cytogenetic abnormalities: -7, -5,&#xD;
             trisomy 8, abnormal 3q, t(6;9), t(9;22) or t(9;11), normal karyotype with FLT3-ITD&#xD;
&#xD;
          -  Age 56 - 65 years with a complex aberrant karyotype defined as &gt;4 cytogenetic&#xD;
             abnormalities&#xD;
&#xD;
          -  Any age with relapsed or refractory disease&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        None of the following should apply:&#xD;
&#xD;
          -  Patient has had immunotherapy including corticosteroids (except Prednisolone &lt;10mg or&#xD;
             equivalent) within the last 4 weeks or is planned to receive such therapy prior to&#xD;
             apheresis of PBMC.&#xD;
&#xD;
          -  Patient has been given chemotherapy and/or G-CSF in the last 4 weeks.&#xD;
&#xD;
          -  Patient has been planned to receive chemotherapy and/or growth factors of any type&#xD;
             before planned apheresis of PBMC&#xD;
&#xD;
          -  Patient has been given experimental therapy within the last 4 weeks or is planned to&#xD;
             receive experimental therapy prior to apheresis of PBMC&#xD;
&#xD;
          -  Patient has known clinically significant autoimmune disease with positive serology for&#xD;
             RHF (&gt;20kU/L) or ANA (titre &gt;1:40)&#xD;
&#xD;
          -  Patient has a history of idiopathic pancreatitis Patient has known, biopsy proven&#xD;
             autoimmune inflammatory disease of the gastrointestinal tract&#xD;
&#xD;
          -  Women of child bearing potential (WOCBP) who are unwilling or unable to use an&#xD;
             effective method of contraception to avoid pregnancy for the entire study period and&#xD;
             for at least 3 months after completion of study treatment.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Men who are unwilling or unable to use an acceptable method of contraception for the&#xD;
             entire study period and for at least 3 months after completion of study treatment if&#xD;
             their sexual partners are WOCBP.&#xD;
&#xD;
          -  Patient has known central nervous system (CNS) disease.&#xD;
&#xD;
          -  Patient has a serious uncontrolled medical disorder which would impair the ability to&#xD;
             receive protocol therapy.&#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>Miles Prince, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peter MacCallum Cancer Centre, Australia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3002</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>December 3, 2012</last_update_submitted>
  <last_update_submitted_qc>December 3, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 4, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
    <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/NCT01716364
org study id: LeYPh1
nct id: NCT01716364
lead sponsor: 
has dmc: Yes
Patients with some forms of acute myeloid leukemia (AML) and multiple myeloma (MM) are not
      cured with conventional therapy and new approaches are needed. For the last 15 years we have
      investigated the potential of using a patient's own T cells (a type of white blood cell
      [WBC]) to eradicate the tumor. We have demonstrated the feasibility of this approach in cell
      culture and animal models of AML and MM. Over the last 5 years we have been preparing to
      treat patients as part of a Phase I (first in human) clinical trial.

      The trial treatment involves collecting the patient's own WBCs from the blood by a standard
      well established and safe process called apheresis. The cells are then cultured in a
      specialized laboratory (under Good Manufacturing Practice conditions, similar to standards
      under which pharmaceuticals are produced) over 12 days to convert the cells to specialized
      tumor-attacking T cells. Early in that culture process the cells are exposed to a virus (that
      is modified so that it cannot infect or replicate outside the special culture conditions)
      that contains a special gene. Via the virus, this gene inserts into the patient's T cells in
      culture and gets incorporated into the T cell's genetic machinery. As the T cells replicate,
      the new gene produces a protein receptor that becomes part of the patient's T cells. This
      protein receptor on the T cells has the capacity to specifically recognize and bind to a
      protein on the leukemia or myeloma cells called the "Lewis Y" antigen.

      After the modified T cells are infused into the patient, they home into the bone marrow (this
      tracking is monitored by special radiological techniques) where the new protein receptor on
      the T cell surface can recognize and bind to the cancer cells (which express Lewis Y). Once
      bound onto the cancer cells, the T cells get activated and subsequently replicate and kill
      the cancer cells. The novelty of this approach is that the T-cells will only kill cells that
      have the Lewis Y on their surface - the cancer cells. Moreover, because there are few normal
      cells in a person's body that carry Lewis Y, this treatment is likely to only have minor side
      effects.

      This gene therapy trial is unique and although the primary purpose is to test the safety of
      this approach, patients will be monitored closely for anti-tumor responses. As the trial
      progresses, the dose of T cells infused will increase, in the hope that this will result in a
      better and stronger immune response to the leukemia or myeloma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events.
time frame: Up to 3 years
measure: Percentage of infused labelled cells localizing in bone marrow
time frame: Up to 3 years
measure: Percentage of infused labelled cells localizing in soft tissue or plasmacytoma.
time frame: Up to 3 years
measure: Presence or absence of anti-LeY positive T-cells in peripheral blood and bone marrow.
time frame: Up to 3 years
measure: Percentage of anti LeY positive T-cells in peripheral blood and bone marrow.
time frame: Up to 3 years
measure: Serum IFN-γ and IL-2 levels.
time frame: Up to 3 years
measure: Presence or absence of autoimmune disease.
time frame: Up to 3 years
measure: Overall response.
time frame: Up to 3 years
measure: Time to progression
time frame: Up to 3 years
measure: Time to treatment failure
time frame: Up to 3 years
measure: Duration of response
time frame: Up to 3 years
measure: Overall survival
time frame: Up to 3 years
measure: Location of labelled re-infused T-cells
time frame: Up to 1 month
measure: LewisY expression assessed with Flow Cytometry in Peripheral Blood and Bone Marrow.
time frame: Up to 3 years
measure: LewisY expression assessed with Flow Cytometry in Peripheral Blood and Bone
time frame: Up to 3 years
arm group label: Anti-LeY- scFv-CD28-ζ vector.
arm group type: Experimental
description: Anti-LeY- scFv-CD28-ζ vector, a non-pathogenic, replication-incompetent retroviral vector specifically designed for this study and produced by EUFETS under GMP-conditions.
intervention type: Biological
intervention name: Anti-LeY- scFv-CD28-ζ vector,.
arm group label: Anti-LeY- scFv-CD28-ζ vector.
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Miles Prince, MD
role: Principal Investigator
affiliation: Peter MacCallum Cancer Centre, Australia
facility: 
country: Australia
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
mesh term: Syndrome