<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/NCT02991898</url>
  </required_header>
  <id_info>
    <org_study_id>2016LS107</org_study_id>
    <secondary_id>MT2016-17</secondary_id>
    <nct_id>NCT02991898</nct_id>
  </id_info>
  <brief_title>Adoptive TReg Cell for Suppression of aGVHD After UCB HSCT for Heme Malignancies</brief_title>
  <official_title>Adoptive Transfer of T Regulatory Cell for Suppression of Acute Graft-vs-Host-Disease After an Umbilical Cord Blood Transplant for Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Masonic Cancer Center, University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Masonic Cancer Center, University of Minnesota</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>
      This is a single center pilot study of a non-myeloablative umbilical cord blood transplant&#xD;
      for the treatment of a hematological malignancy with a single infusion of T regulatory (Treg)&#xD;
      given shortly after UCB transplantation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Considering new technology for product.&#xD;
  </why_stopped>
  <start_date type="Actual">February 16, 2017</start_date>
  <completion_date type="Actual">June 20, 2019</completion_date>
  <primary_completion_date type="Actual">June 20, 2019</primary_completion_date>
  <phase>Phase 2</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 Survived</measure>
    <time_frame>2 years</time_frame>
    <description>Count of patients who survived 2 years post intervention</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Grade II-IV aGVHD</measure>
    <time_frame>Assessed weekly until day 100, then day 180, 360</time_frame>
    <description>Probability of grade II-IV aGVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing Treatment Related Mortality (TRM)</measure>
    <time_frame>6 months</time_frame>
    <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced Relapse</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Incidence of Bacterial, Viral and Fungal Infections</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participant With Detectable Treg Cells at d14</measure>
    <time_frame>14 days</time_frame>
    <description>The proportion of patients with detectable Treg cells at day 14 post infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Immune Reconstitution</measure>
    <time_frame>Assessed at Day 4, weekly for 8 weeks</time_frame>
    <description>The proportion of patients with immune reconstitution. Continuous endpoints will be described by medians, ranges and interquartile ranges as well as means and standard deviations if normally distributed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing Treg Cell Infusion Toxicity</measure>
    <time_frame>48 hours post infusion</time_frame>
    <description>Incidence of Adverse Events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Treg Survival</measure>
    <time_frame>24 hours post infusion</time_frame>
    <description>Length of Treg survival after infusion of Treg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Donor Cell Chimerism</measure>
    <time_frame>Day +100</time_frame>
    <description>The incidence of chimerism in patients treated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Survived One Year Post-transplant</measure>
    <time_frame>1 year</time_frame>
    <description>The probability of survival, one year post-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Neutrophil Recovery</measure>
    <time_frame>Day 42</time_frame>
    <description>The incidence of neutrophil recovery, that is return of neutrophil counts to ≥ 5 X 10^8/L in treated patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Platelet Recovery</measure>
    <time_frame>1 year</time_frame>
    <description>The incidence of platelet recovery (return of platelet counts to &gt; 20,000/μL) in treated patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Chronic GVHD</measure>
    <time_frame>1 year</time_frame>
    <description>The incidence of chronic GVHD in treated patients after one year</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Burkitt Lymphoma</condition>
  <condition>Natural Killer Cell Malignancies</condition>
  <condition>Chronic Myelogenous Leukemia</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <condition>Large-cell Lymphoma</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <condition>Marginal Zone B-Cell Lymphoma</condition>
  <condition>Follicular Lymphoma</condition>
  <condition>Lymphoplasmacytic Lymphoma</condition>
  <condition>Mantle-Cell Lymphoma</condition>
  <condition>Prolymphocytic Leukemia</condition>
  <condition>Hodgkin Lymphoma</condition>
  <condition>Multiple Myeloma</condition>
  <condition>Acute Myelogenous Leukemia</condition>
  <condition>Biphenotypic Leukemia</condition>
  <condition>Undifferentiated Leukemia</condition>
  <arm_group>
    <arm_group_label>Treg Infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Infusion of Treg</intervention_name>
    <description>Allopurinol on day -7 to day 0 Cyclophosphamide 50 mg/kg IV over 2 hours on day -6 Fludarabine 30mg/m2 IV over 1 hour on day -6, -5, -4, -3, and -2 Total Body Irradiation 200 cGy as a single dose&#xD;
Sirolimus 8mg-12mg oral loading dose followed by single dose 4mg/day. Levels are to be monitored 3 times/week in the first week, weekly until day +60, and as clinically indicated until day +100 post-transplantation.&#xD;
Mycophenolate Mofetil (MMF) 3 gram/day IV/PO divided in 2 or 3 doses. Stop MMF at day +30 or 7 days after neutrophil recovery, whichever day is later, if no acute GVHD.&#xD;
DUCBT followed Tregs - double umbilical cord blood transplant (FIRST) followed by the Treg cell infusion (SECOND) no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion.</description>
    <arm_group_label>Treg Infusion</arm_group_label>
    <other_name>T regulatory cells</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be ≥18, but &lt; 70 years of age with no matched 7/8 or 8/8 sibling donor - patients&#xD;
             ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2&#xD;
             (http://www.qxmd.com/calculate-online/hematology/hct-ci)&#xD;
&#xD;
          -  UCB unit(s) composing the graft will be selected according to the current University&#xD;
             of Minnesota umbilical cord blood graft selection algorithm and an additional cord&#xD;
             blood unit to be used as the source to manufacture the Treg product. This UCB unit&#xD;
             must be matched at 4-6/6 to the patient, considering HLA-A, B at the antigen level and&#xD;
             DRB1 at the allele level&#xD;
&#xD;
          -  Acute Leukemias: Must be in remission by morphology. Also a small percentage of blasts&#xD;
             that is equivocal between marrow regeneration versus early relapse are acceptable&#xD;
             provided there are no associated cytogenetic markers consistent with relapse. Refer to&#xD;
             Section 5.2 for complete definitions.&#xD;
&#xD;
          -  Burkitt's Lymphoma in CR2 or subsequent CR&#xD;
&#xD;
          -  Natural Killer Cell Malignancies&#xD;
&#xD;
          -  Chronic Myelogenous Leukemia: all types except refractory blast crisis. Chronic phase&#xD;
             patients must have failed at least two different tyrosine-kinase inhibitors (TKIs), or&#xD;
             been intolerant to all available TKIs or have T315I mutation.&#xD;
&#xD;
          -  Myelodysplastic Syndrome: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO&#xD;
             classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC &lt; 0.8, Anemia or&#xD;
             thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on&#xD;
             IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be be &lt; 5%, preferably &lt;&#xD;
             20% blasts by morphology by bone marrow aspirate morphology.. If ≥ 5% blasts,&#xD;
             chemotherapy for cytoreduction to &lt;5% blasts prior to transplantation may be&#xD;
             considered.&#xD;
&#xD;
          -  Chronic myeloid neoplasms, including but not limited to CMML with blasts must around&#xD;
             5% blasts, preferably &lt; 20% blasts by morphology by bone marrow aspirate morphology.&#xD;
             If ≥5% blasts, chemotherapy for cytoreduction to &lt;5% blasts prior to transplantation&#xD;
             may be considered.&#xD;
&#xD;
          -  Large-Cell Lymphoma, Hodgkin Lymphoma and Multiple Myeloma with chemotherapy sensitive&#xD;
             disease that has failed or patients who are ineligible for an autologous transplant.&#xD;
&#xD;
          -  Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone&#xD;
             B-Cell Lymphoma, Follicular Lymphoma, which have progressed within 12 months of&#xD;
             achieving a partial or complete remission. Patients who had remissions lasting &gt; 12&#xD;
             months are eligible after at least two prior therapies. Patients with bulky disease&#xD;
             should be considered for debulking chemotherapy before transplant. Patients with&#xD;
             refractory disease are eligible, unless has bulky disease and an estimated tumor&#xD;
             doubling time of less than one month.&#xD;
&#xD;
          -  Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible&#xD;
             after initial therapy if chemotherapy sensitive.&#xD;
&#xD;
          -  Patients must have undergone an autologous transplant ≤ 12 months prior to transplant&#xD;
             on this study or have received multi-agent or immunosuppressive chemotherapy within 3&#xD;
             months of the preparative regimen.&#xD;
&#xD;
        Performance Status, Organ Function, Contraception Use&#xD;
&#xD;
          -  Karnofsky score ≥ 70% (Appendix II)&#xD;
&#xD;
          -  Adequate organ function within 14 days (30 days for cardiac and pulmonary) of&#xD;
             registration on-study defined as:&#xD;
&#xD;
               -  Renal: creatinine ≤ 2.0 mg/dL, for patient with a creatinine &gt; 1.2 mg/dL or a&#xD;
                  history of renal dysfunction an estimated glomerular filtration rate ≥ 40&#xD;
                  mL/min/1.73 m2 is required&#xD;
&#xD;
               -  ALT, AST and alkaline phosphatase ≤ 5 x upper limit of normal and total bilirubin&#xD;
                  ≤ 2.5 mg/dL except for patients with Gilbert's syndrome or hemolysis&#xD;
&#xD;
               -  Pulmonary function: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2&#xD;
                  requirements.&#xD;
&#xD;
               -  Cardiac: Absence of decompensated congestive heart failure, or uncontrolled&#xD;
                  arrhythmia and left ventricular ejection fraction ≥ 40%.&#xD;
&#xD;
          -  Sexually active females of childbearing potential and males with partners of&#xD;
             child-bearing potential must agree to use adequate birth control during study&#xD;
             treatment.&#xD;
&#xD;
          -  Voluntary written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Untreated active infection&#xD;
&#xD;
          -  History of HIV infection&#xD;
&#xD;
          -  Pregnant or breast feeding. The agents used in this study may be teratogenic to a&#xD;
             fetus and there is no information on the excretion of agents into breast milk. Females&#xD;
             of childbearing potential must have a blood test or urine study within 14 days prior&#xD;
             to registration to rule out pregnancy&#xD;
&#xD;
          -  Prior allogeneic transplantation&#xD;
&#xD;
          -  Less than 3 months from myeloablative conditioning for autologous transplantation (if&#xD;
             applicable)&#xD;
&#xD;
          -  Evidence of progressive disease by imaging modalities or biopsy - persistent PET&#xD;
             activity, though possibly related to lymphoma, is not an exclusion criterion in the&#xD;
             absence of CT changes indicating progression.&#xD;
&#xD;
          -  CML in blast crisis&#xD;
&#xD;
          -  Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on&#xD;
             salvage therapy.&#xD;
&#xD;
          -  Active central nervous system malignancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claudio Brunstein, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Masonic Cancer Center, University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Masonic Cancer Center at University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <results_first_submitted>June 17, 2020</results_first_submitted>
  <results_first_submitted_qc>July 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 24, 2020</results_first_posted>
  <last_update_submitted>September 8, 2020</last_update_submitted>
  <last_update_submitted_qc>September 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CML</keyword>
  <keyword>MDS</keyword>
  <keyword>CLL</keyword>
  <keyword>ALL</keyword>
  <keyword>AML</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burkitt Lymphoma</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Leukemia, Prolymphocytic</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 4, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT02991898/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treg Infusion</title>
          <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treg Infusion</title>
          <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Survived</title>
        <description>Count of patients who survived 2 years post intervention</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Survived</title>
          <description>Count of patients who survived 2 years post intervention</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Grade II-IV aGVHD</title>
        <description>Probability of grade II-IV aGVHD</description>
        <time_frame>Assessed weekly until day 100, then day 180, 360</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Grade II-IV aGVHD</title>
          <description>Probability of grade II-IV aGVHD</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing Treatment Related Mortality (TRM)</title>
        <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing Treatment Related Mortality (TRM)</title>
          <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced Relapse</title>
        <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced Relapse</title>
          <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Incidence of Bacterial, Viral and Fungal Infections</title>
        <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Incidence of Bacterial, Viral and Fungal Infections</title>
          <description>Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Bacterial</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Viral</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Fungal</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participant With Detectable Treg Cells at d14</title>
        <description>The proportion of patients with detectable Treg cells at day 14 post infusion</description>
        <time_frame>14 days</time_frame>
        <population>Samples were not analyzed, and so data not available for reporting.</population>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participant With Detectable Treg Cells at d14</title>
          <description>The proportion of patients with detectable Treg cells at day 14 post infusion</description>
          <population>Samples were not analyzed, and so data not available for reporting.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Immune Reconstitution</title>
        <description>The proportion of patients with immune reconstitution. Continuous endpoints will be described by medians, ranges and interquartile ranges as well as means and standard deviations if normally distributed.</description>
        <time_frame>Assessed at Day 4, weekly for 8 weeks</time_frame>
        <population>Samples were not analyzed, and so data not available for reporting.</population>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Immune Reconstitution</title>
          <description>The proportion of patients with immune reconstitution. Continuous endpoints will be described by medians, ranges and interquartile ranges as well as means and standard deviations if normally distributed.</description>
          <population>Samples were not analyzed, and so data not available for reporting.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing Treg Cell Infusion Toxicity</title>
        <description>Incidence of Adverse Events</description>
        <time_frame>48 hours post infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing Treg Cell Infusion Toxicity</title>
          <description>Incidence of Adverse Events</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Treg Survival</title>
        <description>Length of Treg survival after infusion of Treg.</description>
        <time_frame>24 hours post infusion</time_frame>
        <population>Samples were not analyzed, and so data not available for reporting.</population>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Treg Survival</title>
          <description>Length of Treg survival after infusion of Treg.</description>
          <population>Samples were not analyzed, and so data not available for reporting.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Donor Cell Chimerism</title>
        <description>The incidence of chimerism in patients treated</description>
        <time_frame>Day +100</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Donor Cell Chimerism</title>
          <description>The incidence of chimerism in patients treated</description>
          <units>percentage of donor cells</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72" lower_limit="50" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Survived One Year Post-transplant</title>
        <description>The probability of survival, one year post-treatment</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Survived One Year Post-transplant</title>
          <description>The probability of survival, one year post-treatment</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Neutrophil Recovery</title>
        <description>The incidence of neutrophil recovery, that is return of neutrophil counts to ≥ 5 X 10^8/L in treated patients</description>
        <time_frame>Day 42</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Neutrophil Recovery</title>
          <description>The incidence of neutrophil recovery, that is return of neutrophil counts to ≥ 5 X 10^8/L in treated patients</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Platelet Recovery</title>
        <description>The incidence of platelet recovery (return of platelet counts to &gt; 20,000/μL) in treated patients</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Platelet Recovery</title>
          <description>The incidence of platelet recovery (return of platelet counts to &gt; 20,000/μL) in treated patients</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Chronic GVHD</title>
        <description>The incidence of chronic GVHD in treated patients after one year</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treg Infusion</title>
            <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Chronic GVHD</title>
          <description>The incidence of chronic GVHD in treated patients after one year</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 week</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treg Infusion</title>
          <description>The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Graft Versus Host Disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Capillary leak syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cytokine release syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="7" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Claudio Brunstein</name_or_title>
      <organization>Masonic Cancer Center, University of Minnesota</organization>
      <phone>612-625-3918</phone>
      <email>bruns072@umn.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02991898
org study id: 2016LS107
secondary id: MT2016-17
nct id: NCT02991898
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a single center pilot study of a non-myeloablative umbilical cord blood transplant
      for the treatment of a hematological malignancy with a single infusion of T regulatory (Treg)
      given shortly after UCB transplantation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants Survived
time frame: 2 years
description: Count of patients who survived 2 years post intervention
measure: Number of Participants With Grade II-IV aGVHD
time frame: Assessed weekly until day 100, then day 180, 360
description: Probability of grade II-IV aGVHD
measure: Number of Participants Experiencing Treatment Related Mortality (TRM)
time frame: 6 months
description: Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.
measure: Number of Participants Who Experienced Relapse
time frame: 1 year
description: Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.
measure: Number of Participants With Incidence of Bacterial, Viral and Fungal Infections
time frame: 1 year
description: Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.
measure: Number of Participant With Detectable Treg Cells at d14
time frame: 14 days
description: The proportion of patients with detectable Treg cells at day 14 post infusion
measure: Number of Participants With Immune Reconstitution
time frame: Assessed at Day 4, weekly for 8 weeks
description: The proportion of patients with immune reconstitution. Continuous endpoints will be described by medians, ranges and interquartile ranges as well as means and standard deviations if normally distributed.
measure: Number of Participants Experiencing Treg Cell Infusion Toxicity
time frame: 48 hours post infusion
description: Incidence of Adverse Events
measure: Length of Treg Survival
time frame: 24 hours post infusion
description: Length of Treg survival after infusion of Treg.
measure: Percentage of Donor Cell Chimerism
time frame: Day +100
description: The incidence of chimerism in patients treated
measure: Number of Participants Survived One Year Post-transplant
time frame: 1 year
description: The probability of survival, one year post-treatment
measure: Number of Participants With Neutrophil Recovery
time frame: Day 42
description: The incidence of neutrophil recovery, that is return of neutrophil counts to ≥ 5 X 10^8/L in treated patients
measure: Number of Participants With Platelet Recovery
time frame: 1 year
description: The incidence of platelet recovery (return of platelet counts to > 20,000/μL) in treated patients
measure: Number of Participants With Chronic GVHD
time frame: 1 year
description: The incidence of chronic GVHD in treated patients after one year
arm group label: Treg Infusion
arm group type: Experimental
description: The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion
intervention type: Biological
intervention name: Infusion of Treg
description: Allopurinol on day -7 to day 0 Cyclophosphamide 50 mg/kg IV over 2 hours on day -6 Fludarabine 30mg/m2 IV over 1 hour on day -6, -5, -4, -3, and -2 Total Body Irradiation 200 cGy as a single dose
Sirolimus 8mg-12mg oral loading dose followed by single dose 4mg/day. Levels are to be monitored 3 times/week in the first week, weekly until day +60, and as clinically indicated until day +100 post-transplantation.
Mycophenolate Mofetil (MMF) 3 gram/day IV/PO divided in 2 or 3 doses. Stop MMF at day +30 or 7 days after neutrophil recovery, whichever day is later, if no acute GVHD.
DUCBT followed Tregs - double umbilical cord blood transplant (FIRST) followed by the Treg cell infusion (SECOND) no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion.
arm group label: Treg Infusion
other name: T regulatory cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Claudio Brunstein, MD, PhD
role: Principal Investigator
affiliation: Masonic Cancer Center, University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Burkitt Lymphoma
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Multiple Myeloma
mesh term: Neoplasms
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Leukemia, Myeloid
mesh term: Lymphoma, Mantle-Cell
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Leukemia, Myeloid, Acute
mesh term: Leukemia, Prolymphocytic
mesh term: Waldenstrom Macroglobulinemia
mesh term: Myelodysplastic Syndromes
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 