<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/NCT02259348</url>
  </required_header>
  <id_info>
    <org_study_id>REFNK1</org_study_id>
    <secondary_id>NCI-2014-01925</secondary_id>
    <nct_id>NCT02259348</nct_id>
  </id_info>
  <brief_title>Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation</brief_title>
  <official_title>CD45A-Depleted Haploidentical Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Jude Children's Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Jude Children's Research Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot phase II trial studies how well a new reduced intensity conditioning regimen that&#xD;
      includes haploidentical donor NK cells followed by the infusion of selectively T-cell&#xD;
      depleted progenitor cell grafts work in treating younger patients with hematologic&#xD;
      malignancies that have returned after or did not respond to treatment with a prior&#xD;
      transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell&#xD;
      transplant may help stop the growth of cells in the bone marrow, including normal&#xD;
      blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's&#xD;
      immune system from rejecting the donor's cells. When the healthy progenitor cells from a&#xD;
      related donor are infused into the patient they make red blood cells, white blood cells, and&#xD;
      platelets. Sometimes the transplanted cells from a donor can make an immune response against&#xD;
      the body's normal cells (called graft-versus-host disease). Removing specific T cells from&#xD;
      the donor cells before the transplant may prevent this.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
        -  To estimate engraftment by day +42 post-transplant in patients who receive&#xD;
           CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced&#xD;
           intensity conditioning regimen that includes haploidentical natural killer (NK) cells.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
        -  Estimate the incidence of malignant relapse, event-free survival, and overall survival&#xD;
           at one-year post-transplantation.&#xD;
&#xD;
        -  Estimate incidence and severity of acute and chronic (GvHD).&#xD;
&#xD;
        -  Estimate the rate of transplant related mortality (TRM) in the first 100 days after&#xD;
           transplantation.&#xD;
&#xD;
      Blood progenitor cells will be collected from adult donors to be used for transplantation.&#xD;
      Donor cells will be processed and filtered in a laboratory at St. Jude using a machine called&#xD;
      the CliniMACS™ device, and later infused (transplanted) into the participant through his/her&#xD;
      veins.&#xD;
&#xD;
      Participants undergo a conditioning regimen beginning Day 21 prior to progenitor cell&#xD;
      transplantation that includes chemotherapy medications and natural killer cells in&#xD;
      preparation for transplantation. They will then receive T-cell depleted HPC transplant&#xD;
      followed by CD45RA-depleted HPC transplant the following day.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Investigator's decision.&#xD;
  </why_stopped>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">April 2015</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>Percentage of Participants Engrafted by Day 42 Post-transplant</measure>
    <time_frame>Day 42 post transplantation</time_frame>
    <description>To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. Engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Malignant Relapse</measure>
    <time_frame>one year post transplantation</time_frame>
    <description>The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The number of participants with incidence of malignant relapse is given. Relapse was evaluated using standard WHO criteria for each disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free Survival (EFS)</measure>
    <time_frame>one year post transplantation</time_frame>
    <description>The Kaplan-Meier estimate of event-free survival (EFS) along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where EFS = min (date of last follow-up, date of relapse, date of graft failure, date of death due to any cause) - date of transplant, and all participants surviving at the time of analysis without events will be censored. The number of participants who did not experience any of these events through one year post-transplant is given.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>one year post transplantation</time_frame>
    <description>The Kaplan-Meier estimate of OS along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where OS = min (date of last follow-up, date of death) - date of transplant and all participants surviving at the time of analysis without events will be censored. The number of participants surviving to one-year post-transplantation is given.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of Acute GvHD</measure>
    <time_frame>100 days post transplantation</time_frame>
    <description>The cumulative incidence of acute GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of acute GvHD. The number of participants with incidence by grade is given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of Chronic GvHD</measure>
    <time_frame>one year post transplantation</time_frame>
    <description>The cumulative incidence of chronic GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of chronic GvHD will be described. Chronic GvHD was evaluated using NIH Consensus Global Severity Scoring.&quot; The number of participants with incidence by severity is given.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Transplant-related Mortality (TRM)</measure>
    <time_frame>100 days post transplantation</time_frame>
    <description>The cumulative incidence of transplant related mortality will be estimated using Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the competing risk events.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Acute Lymphoblastic Leukemia (ALL)</condition>
  <condition>Acute Myeloid Leukemia (AML)</condition>
  <condition>Myeloid Sarcoma</condition>
  <condition>Chronic Myelogenous Leukemia (CML)</condition>
  <condition>Juvenile Myelomonocytic Leukemia (JMML)</condition>
  <condition>Myelodysplastic Syndrome (MDS)</condition>
  <condition>Non-Hodgkin Lymphoma (NHL)</condition>
  <arm_group>
    <arm_group_label>Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>Cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>Fludara</other_name>
    <other_name>Fludarabine monophosphate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>G-CSF</intervention_name>
    <description>Given IV or subcutaneously (SQ)</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>Filgrastim</other_name>
    <other_name>Neupogen®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Interleukin-2</intervention_name>
    <description>Given SQ</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>IL-2</other_name>
    <other_name>Aldesleukin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>L-phenylalanine mustard</other_name>
    <other_name>Phenylalanine mustard</other_name>
    <other_name>L-PAM</other_name>
    <other_name>L-sarcolysin</other_name>
    <other_name>Alkeran®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thiotepa</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>ThioplexV</other_name>
    <other_name>TESPA</other_name>
    <other_name>TSPA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>Rituxan™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Natural killer cell therapy</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>NK cell therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>T-cell depleted HPC transplant</intervention_name>
    <description>T-cell depleted hematopoietic stem cells will be infused on day 0.</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>HPC,A Infusion(ɑ/β T cell depleted)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD45RA-depleted HPC transplant</intervention_name>
    <description>CD45RA depleted stem cells will be infused on day 1.</description>
    <arm_group_label>Participants</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age less than or equal to 21 years.&#xD;
&#xD;
          -  One of the following hematologic malignancies that has relapsed or remains refractory&#xD;
             after prior allogeneic hematopoietic cell transplant (HCT):&#xD;
&#xD;
               -  ALL, AML, Myeloid Sarcoma, CML, Juvenile myelomonocytic leukemia (JMML),&#xD;
                  myelodysplastic syndrome (MDS), non-Hodgkin lymphoma (NHL)&#xD;
&#xD;
          -  Has a suitable single haplotype matched (≥ 3 of 6) family member donor.&#xD;
&#xD;
          -  Does not have any other active malignancy other than the one for which this transplant&#xD;
             is indicated.&#xD;
&#xD;
          -  If prior central nervous system (CNS) leukemia, it must be treated and in CNS complete&#xD;
             remission (CR)&#xD;
&#xD;
          -  Does not have current uncontrolled bacterial, fungal, or viral infection.&#xD;
&#xD;
          -  Patient must fulfill pre-transplant evaluation:&#xD;
&#xD;
          -  Left ventricular ejection fraction &gt; 40%, or shortening fraction ≥ 25%.&#xD;
&#xD;
          -  Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2.&#xD;
&#xD;
          -  Forced vital capacity (FVC) ≥ 40% of predicted value; or pulse oximetry ≥ 92% on room&#xD;
             air if patient is unable to perform pulmonary function testing.&#xD;
&#xD;
          -  Karnofsky or Lansky (age-dependent) performance score ≥ 50 (See Appendix A).&#xD;
&#xD;
          -  Bilirubin ≤ 3 times the upper limit of normal for age.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age.&#xD;
&#xD;
          -  Not pregnant. If female with child bearing potential, must be confirmed by negative&#xD;
             serum or urine pregnancy test within 14 days prior to enrollment.&#xD;
&#xD;
          -  Not breast feeding&#xD;
&#xD;
          -  DONOR: At least single haplotype matched (≥ 3 of 6) family member&#xD;
&#xD;
          -  DONOR: At least 18 years of age.&#xD;
&#xD;
          -  DONOR: HIV negative.&#xD;
&#xD;
          -  DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14&#xD;
             days prior to enrollment (if female).&#xD;
&#xD;
          -  DONOR: Not breast feeding.&#xD;
&#xD;
          -  DONOR: Regarding donation eligibility, is identified as either:&#xD;
&#xD;
               -  Completed the process of donor eligibility determination as outlined in 21 CFR&#xD;
                  1271 and agency guidance; OR&#xD;
&#xD;
               -  Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of&#xD;
                  urgent medical need completed by the principal investigator or physician&#xD;
                  sub-investigator per 21 CFR 1271.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brandon Triplett, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.stjude.org</url>
    <description>St. Jude Children's Research Hospital</description>
  </link>
  <link>
    <url>http://www.stjude.org/protocols</url>
    <description>Clinical Trials Open at St. Jude</description>
  </link>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <results_first_submitted>March 10, 2016</results_first_submitted>
  <results_first_submitted_qc>April 12, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 2, 2016</results_first_posted>
  <last_update_submitted>April 24, 2017</last_update_submitted>
  <last_update_submitted_qc>April 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hematological malignancies</keyword>
  <keyword>Allogeneic hematopoietic cell transplant</keyword>
  <keyword>Refractory hematologic malignancy</keyword>
  <keyword>Relapsed hematologic malignancy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Juvenile</mesh_term>
    <mesh_term>Sarcoma, Myeloid</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aldesleukin</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Melphalan</mesh_term>
    <mesh_term>Mechlorethamine</mesh_term>
    <mesh_term>Thiotepa</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
    <mesh_term>Interleukin-2</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Twelve participants meeting eligibility criteria were enrolled at St. Jude Children's Research Hospital between November 2014 and February 2015.</recruitment_details>
      <pre_assignment_details>Six enrolled participants were blood donors and did not undergo transplantation.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Participants</title>
          <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>One Year Post-transplant</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Donors</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Participants</title>
          <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12.6" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <title>Age, Median</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12.2" lower_limit="6.7" upper_limit="19.5"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Not otherwise specified Spanish, Hispanic, Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non Spanish speaking, Non Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary Diagnosis</title>
          <description>AML = acute myeloid leukemia; MLL = myeloid-lymphoid leukemia; MDS = myelodysplastic syndrome</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>AML with 11q23/MLL abnormalities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AML, multilineage dysplasia with prior MDS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AML, not otherwise specified</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AML, without maturation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Engrafted by Day 42 Post-transplant</title>
        <description>To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. Engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.</description>
        <time_frame>Day 42 post transplantation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Engrafted by Day 42 Post-transplant</title>
          <description>To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. Engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Malignant Relapse</title>
        <description>The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The number of participants with incidence of malignant relapse is given. Relapse was evaluated using standard WHO criteria for each disease.</description>
        <time_frame>one year post transplantation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Malignant Relapse</title>
          <description>The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The number of participants with incidence of malignant relapse is given. Relapse was evaluated using standard WHO criteria for each disease.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </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>Event-free Survival (EFS)</title>
        <description>The Kaplan-Meier estimate of event-free survival (EFS) along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where EFS = min (date of last follow-up, date of relapse, date of graft failure, date of death due to any cause) - date of transplant, and all participants surviving at the time of analysis without events will be censored. The number of participants who did not experience any of these events through one year post-transplant is given.</description>
        <time_frame>one year post transplantation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-free Survival (EFS)</title>
          <description>The Kaplan-Meier estimate of event-free survival (EFS) along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where EFS = min (date of last follow-up, date of relapse, date of graft failure, date of death due to any cause) - date of transplant, and all participants surviving at the time of analysis without events will be censored. The number of participants who did not experience any of these events through one year post-transplant is given.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </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>Overall Survival (OS)</title>
        <description>The Kaplan-Meier estimate of OS along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where OS = min (date of last follow-up, date of death) - date of transplant and all participants surviving at the time of analysis without events will be censored. The number of participants surviving to one-year post-transplantation is given.</description>
        <time_frame>one year post transplantation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>The Kaplan-Meier estimate of OS along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where OS = min (date of last follow-up, date of death) - date of transplant and all participants surviving at the time of analysis without events will be censored. The number of participants surviving to one-year post-transplantation is given.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </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>Incidence and Severity of Acute GvHD</title>
        <description>The cumulative incidence of acute GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of acute GvHD. The number of participants with incidence by grade is given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.</description>
        <time_frame>100 days post transplantation</time_frame>
        <population>Two of six participants did not experience any acute GvHD.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence and Severity of Acute GvHD</title>
          <description>The cumulative incidence of acute GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of acute GvHD. The number of participants with incidence by grade is given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.</description>
          <population>Two of six participants did not experience any acute GvHD.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade IV</title>
              <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>Incidence and Severity of Chronic GvHD</title>
        <description>The cumulative incidence of chronic GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of chronic GvHD will be described. Chronic GvHD was evaluated using NIH Consensus Global Severity Scoring.&quot; The number of participants with incidence by severity is given.</description>
        <time_frame>one year post transplantation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence and Severity of Chronic GvHD</title>
          <description>The cumulative incidence of chronic GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of chronic GvHD will be described. Chronic GvHD was evaluated using NIH Consensus Global Severity Scoring.&quot; The number of participants with incidence by severity is given.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mild</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severe</title>
              <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>Rate of Transplant-related Mortality (TRM)</title>
        <description>The cumulative incidence of transplant related mortality will be estimated using Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the competing risk events.</description>
        <time_frame>100 days post transplantation</time_frame>
        <population>All six participants who received the protocol-defined treatment were evaluable for this analysis. One participant died of a non-transplant related cause (leukemia) prior to day 100. Although this participant did not complete the study to Day 100 post-transplantation, they were still evaluable for TRM.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Transplant-related Mortality (TRM)</title>
          <description>The cumulative incidence of transplant related mortality will be estimated using Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the competing risk events.</description>
          <population>All six participants who received the protocol-defined treatment were evaluable for this analysis. One participant died of a non-transplant related cause (leukemia) prior to day 100. Although this participant did not complete the study to Day 100 post-transplantation, they were still evaluable for TRM.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </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>Post-Hoc</type>
        <title>Mean of Days to Absolute Neutrophil Count (ANC) Engraftment</title>
        <description>ANC engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.</description>
        <time_frame>Day 42 post transplantation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean of Days to Absolute Neutrophil Count (ANC) Engraftment</title>
          <description>ANC engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3" spread="1.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Median Days to Absolute Neutrophil Count (ANC) Engraftment</title>
        <description>ANC engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.</description>
        <time_frame>Day 42 post transplantation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants</title>
            <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Days to Absolute Neutrophil Count (ANC) Engraftment</title>
          <description>ANC engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="9" upper_limit="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from study enrollment through off-study date (up to 16 months).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Participants</title>
          <description>Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.&#xD;
Cyclophosphamide: Given intravenously (IV)&#xD;
Fludarabine: Given IV&#xD;
G-CSF: Given IV or subcutaneously (SQ)&#xD;
Interleukin-2: Given SQ&#xD;
Melphalan: Given IV&#xD;
Thiotepa: Given IV&#xD;
Rituximab: Given IV&#xD;
Natural killer cell therapy: Given IV&#xD;
T-cell depleted HPC transplant: T-cell depleted hematopoietic stem cells will be infused on day 0.&#xD;
CD45RA-depleted HPC transplant: CD45RA depleted stem cells will be infused on day 1.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (3.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hemorrhage, pulmonary</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure (disorder)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection, candida glabrata, GI tract</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, culture negative, sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, enterococcus faecalis, blood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, escherichia coli, blood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, klebsiella oxytoca, blood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, pseudomonas aeruginosa, blood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, staphylococcus epidermidis, blood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, toxoplasmosis, cerebrospinal fluid</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Failure, renal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cryptogenic organizing pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Failure, pulmonary</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Respiratory failure (disorder)</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (3.0)</default_vocab>
        <default_assessment>Non-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="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Left ventricular systolic dysfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mucositis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pneumatosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hemorrhage, gastrointestinal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Acute infusion reaction, boost</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Acute infusion reaction, granulocyte</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Acute infusion reaciton, NK cells</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Acute infusion reaction, stem cells</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cytokine release syndrome, ATG</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Engraftment syndrome</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Systemic inflammatory response syndrome (disorder)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Tumor lysis syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess, mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, adenovirus, respiratory tract</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, adenovirus, stool</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, BK virus, blood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, BK virus, urine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, candida albicans, oral mucosa</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, candida albicans, tracheostomy site</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, candida guilliermondii, blood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, candida lusitaniae, small intestine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, clostridium difficile, stool</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, coagulase negative staphylococcus, pleural fluid</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, disseminated fungus, organism unknown</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, enterobacter cloacae, trachael aspirate</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, human herpes virus 6, blood</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, rotavirus, stool</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, staphylococcus epidermidis, blood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infection, upper respiratory</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Hallucinations (finding)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Involuntary movement (finding)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Failure, renal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchiolitis obliterans organizing pneumonia (disorder)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infiltrates, pulmonary</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </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>
    <limitations_and_caveats>The trial was terminated early due to investigator's decision.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Brandon M. Triplett, MD</name_or_title>
      <organization>St. Jude Children's Research Hospital</organization>
      <phone>901-595-2766</phone>
      <email>brandon.triplett@stjude.org</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/NCT02259348
org study id: REFNK1
secondary id: NCI-2014-01925
nct id: NCT02259348
lead sponsor: 
has dmc: No
This pilot phase II trial studies how well a new reduced intensity conditioning regimen that
      includes haploidentical donor NK cells followed by the infusion of selectively T-cell
      depleted progenitor cell grafts work in treating younger patients with hematologic
      malignancies that have returned after or did not respond to treatment with a prior
      transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell
      transplant may help stop the growth of cells in the bone marrow, including normal
      blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's
      immune system from rejecting the donor's cells. When the healthy progenitor cells from a
      related donor are infused into the patient they make red blood cells, white blood cells, and
      platelets. Sometimes the transplanted cells from a donor can make an immune response against
      the body's normal cells (called graft-versus-host disease). Removing specific T cells from
      the donor cells before the transplant may prevent this.
PRIMARY OBJECTIVE:

        -  To estimate engraftment by day +42 post-transplant in patients who receive
           CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced
           intensity conditioning regimen that includes haploidentical natural killer (NK) cells.

      SECONDARY OBJECTIVES:

        -  Estimate the incidence of malignant relapse, event-free survival, and overall survival
           at one-year post-transplantation.

        -  Estimate incidence and severity of acute and chronic (GvHD).

        -  Estimate the rate of transplant related mortality (TRM) in the first 100 days after
           transplantation.

      Blood progenitor cells will be collected from adult donors to be used for transplantation.
      Donor cells will be processed and filtered in a laboratory at St. Jude using a machine called
      the CliniMACS™ device, and later infused (transplanted) into the participant through his/her
      veins.

      Participants undergo a conditioning regimen beginning Day 21 prior to progenitor cell
      transplantation that includes chemotherapy medications and natural killer cells in
      preparation for transplantation. They will then receive T-cell depleted HPC transplant
      followed by CD45RA-depleted HPC transplant the following day.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Engrafted by Day 42 Post-transplant
time frame: Day 42 post transplantation
description: To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. Engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.
measure: Incidence of Malignant Relapse
time frame: one year post transplantation
description: The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The number of participants with incidence of malignant relapse is given. Relapse was evaluated using standard WHO criteria for each disease.
measure: Event-free Survival (EFS)
time frame: one year post transplantation
description: The Kaplan-Meier estimate of event-free survival (EFS) along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where EFS = min (date of last follow-up, date of relapse, date of graft failure, date of death due to any cause) - date of transplant, and all participants surviving at the time of analysis without events will be censored. The number of participants who did not experience any of these events through one year post-transplant is given.
measure: Overall Survival (OS)
time frame: one year post transplantation
description: The Kaplan-Meier estimate of OS along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where OS = min (date of last follow-up, date of death) - date of transplant and all participants surviving at the time of analysis without events will be censored. The number of participants surviving to one-year post-transplantation is given.
measure: Incidence and Severity of Acute GvHD
time frame: 100 days post transplantation
description: The cumulative incidence of acute GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of acute GvHD. The number of participants with incidence by grade is given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.
measure: Incidence and Severity of Chronic GvHD
time frame: one year post transplantation
description: The cumulative incidence of chronic GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of chronic GvHD will be described. Chronic GvHD was evaluated using NIH Consensus Global Severity Scoring." The number of participants with incidence by severity is given.
measure: Rate of Transplant-related Mortality (TRM)
time frame: 100 days post transplantation
description: The cumulative incidence of transplant related mortality will be estimated using Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the competing risk events.
arm group label: Participants
arm group type: Experimental
description: Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
intervention type: Drug
intervention name: Cyclophosphamide
description: Given intravenously (IV)
arm group label: Participants
other name: Cytoxan
intervention type: Drug
intervention name: Fludarabine
description: Given IV
arm group label: Participants
other name: Fludara
other name: Fludarabine monophosphate
intervention type: Biological
intervention name: G-CSF
description: Given IV or subcutaneously (SQ)
arm group label: Participants
other name: Filgrastim
other name: Neupogen®
intervention type: Biological
intervention name: Interleukin-2
description: Given SQ
arm group label: Participants
other name: IL-2
other name: Aldesleukin
intervention type: Drug
intervention name: Melphalan
description: Given IV
arm group label: Participants
other name: L-phenylalanine mustard
other name: Phenylalanine mustard
other name: L-PAM
other name: L-sarcolysin
other name: Alkeran®
intervention type: Drug
intervention name: Thiotepa
description: Given IV
arm group label: Participants
other name: ThioplexV
other name: TESPA
other name: TSPA
intervention type: Drug
intervention name: Rituximab
description: Given IV
arm group label: Participants
other name: Rituxan™
intervention type: Biological
intervention name: Natural killer cell therapy
description: Given IV
arm group label: Participants
other name: NK cell therapy
intervention type: Biological
intervention name: T-cell depleted HPC transplant
description: T-cell depleted hematopoietic stem cells will be infused on day 0.
arm group label: Participants
other name: HPC,A Infusion(ɑ/β T cell depleted)
intervention type: Biological
intervention name: CD45RA-depleted HPC transplant
description: CD45RA depleted stem cells will be infused on day 1.
arm group label: Participants
criteria: 
gender: All
minimum age: N/A
maximum age: 21 Years
healthy volunteers: No
last name: Brandon Triplett, MD
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
facility: 
country: United States
url: http://www.stjude.org
description: St. Jude Children's Research Hospital
url: http://www.stjude.org/protocols
description: Clinical Trials Open at St. Jude
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid, Acute
mesh term: Neoplasms
mesh term: Lymphoma, Non-Hodgkin
mesh term: Preleukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Hematologic Neoplasms
mesh term: Leukemia, Myelomonocytic, Juvenile
mesh term: Sarcoma, Myeloid
mesh term: Myelodysplastic Syndromes
mesh term: Aldesleukin
mesh term: Cyclophosphamide
mesh term: Melphalan
mesh term: Mechlorethamine
mesh term: Thiotepa
mesh term: Rituximab
mesh term: Fludarabine
mesh term: Fludarabine phosphate
mesh term: Interleukin-2
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The trial was terminated early due to investigator's decision.
point of contact: 