<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/NCT02224872</url>
  </required_header>
  <id_info>
    <org_study_id>J1424</org_study_id>
    <secondary_id>IRB00031590</secondary_id>
    <nct_id>NCT02224872</nct_id>
  </id_info>
  <brief_title>Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia</brief_title>
  <official_title>A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Our primary objective is to determine if it is feasible for SAA patients to be transplanted&#xD;
      using non-myeloablative conditioning and post transplantation cyclophosphamide with partially&#xD;
      HLA-mismatched donors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research is being done to find out if bone marrow transplantation (BMT) followed by&#xD;
      chemotherapy will help people with aplastic anemia who have failed other treatments.&#xD;
&#xD;
      You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow.&#xD;
      Your disease has come back or not responded after receiving one or more immunosuppressive&#xD;
      treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been&#xD;
      used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD)&#xD;
      and graft failure have limited the survival for those people.&#xD;
&#xD;
      A small study done at Johns Hopkins has shown that in subjects with other diseases (blood&#xD;
      cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects&#xD;
      had complications of GVHD and engraftment failure.&#xD;
&#xD;
      People with aplastic anemia who have refractory disease (not responding to standard&#xD;
      treatment) may join.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">December 2021</completion_date>
  <primary_completion_date type="Actual">December 2021</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>Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?</measure>
    <time_frame>1 year</time_frame>
    <description>Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients That Have Survived at One Year</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant</measure>
    <time_frame>60 days</time_frame>
    <description>Donor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with &gt;5% donor chimerism around day 60 will be considered as having engrafted.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Major Toxicities Related to Transplant</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients That Expired Due to Transplant Related Mortality</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Primary or Secondary Graft Failure Following Transplant</measure>
    <time_frame>1 year</time_frame>
    <description>Graft failure: &lt; 5% donor chimerism in blood and/or bone marrow on ~Day 30 or after and on all subsequent measurements.&#xD;
Primary graft failure: &lt; 5% donor chimerism in blood and/or bone marrow by ~ Day 56 Secondary graft failure: achievement of &gt; 5% donor chimerism, followed by sustained &lt;5% donor chimerism in blood and/or bone marrow.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Grade II-IV or Grade III-IV Acute GVHD</measure>
    <time_frame>1 year</time_frame>
    <description>Participants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Chronic GVHD at One Year</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant</measure>
    <time_frame>1 year</time_frame>
    <description>CBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC &gt; 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants That Were GVHD Free, Relapse Free Survival (GRFS)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Severe Aplastic Anemia</condition>
  <condition>Bone Marrow Failure Syndromes</condition>
  <arm_group>
    <arm_group_label>Bone marrow transplant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Bone marrow transplant</intervention_name>
    <description>Day 0</description>
    <arm_group_label>Bone marrow transplant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thymoglobulin</intervention_name>
    <description>0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7</description>
    <arm_group_label>Bone marrow transplant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>30 mg/M2 IV on days -6 to -2</description>
    <arm_group_label>Bone marrow transplant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>14.5 mg/kg IV on days -6, -5, 3, 4</description>
    <arm_group_label>Bone marrow transplant</arm_group_label>
    <other_name>CTX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>TBI</intervention_name>
    <description>200 cGy on day -1</description>
    <arm_group_label>Bone marrow transplant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mesna</intervention_name>
    <description>40 mg/kg IV on days 3, 4</description>
    <arm_group_label>Bone marrow transplant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present</description>
    <arm_group_label>Bone marrow transplant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolic acid mofetil</intervention_name>
    <description>15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
    <arm_group_label>Bone marrow transplant</arm_group_label>
    <other_name>MMF</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with relapsed or refractory SAA or very SAA defined:&#xD;
&#xD;
               -  Bone marrow (&lt; 25% cellular)&#xD;
&#xD;
               -  Peripheral cytopenias (at least 2 of 3)&#xD;
&#xD;
                    -  ANC &lt; 500 per ml&#xD;
&#xD;
                    -  Platelets &lt; 20,000 per ml&#xD;
&#xD;
                    -  Absolute retic &lt; 60,000 or corrected retic &lt; 1%&#xD;
&#xD;
               -  Very severe: as above, but ANC &lt; 200&#xD;
&#xD;
               -  Disease may be designated as acquired or inherited if previous counts known&#xD;
                  (these other bone marrow failure disorders that are characterized by aplastic&#xD;
                  anemia may go by additional names such as dyskeratosis congenita or PNH)&#xD;
&#xD;
               -  Failed at least one course of immunosuppressive therapy (if presumed acquired&#xD;
                  disease). Patients with inherited disease will be characterized as refractory and&#xD;
                  do not require immunosuppressive first.&#xD;
&#xD;
          -  Age 0- upper age limit as determined by current institutional standards&#xD;
&#xD;
          -  Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)&#xD;
&#xD;
          -  Patients and donors must be able to sign consent forms (or if a minor the parent will&#xD;
             sign). Donors should be willing to donate.&#xD;
&#xD;
          -  Patients must be geographically accessible and willing to participate in all stages of&#xD;
             treatment.&#xD;
&#xD;
          -  Adequate end-organ function as measured by:&#xD;
&#xD;
               1. Left ventricular ejection fraction &gt; or = to 35%, or shortening fraction &gt; 25%&#xD;
                  (For pediatric patients, a normal ejection fraction is required)&#xD;
&#xD;
               2. Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT&#xD;
                  and AST ≤ 5 x ULN&#xD;
&#xD;
               3. FEV1 and FVC &gt; or = to 40% of predicted; or in pediatric patients, if unable to&#xD;
                  perform pulmonary function tests due to young age, oxygen saturation &gt;92% on room&#xD;
                  air&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients will not be excluded on the basis of sex, racial or ethnic background.&#xD;
&#xD;
          -  Prior transfusions from selected donor (as this could have cause recipient&#xD;
             alloimmunization against the donor)&#xD;
&#xD;
          -  Women of childbearing potential who currently are pregnant (HCG+) or who are not&#xD;
             practicing adequate contraception.&#xD;
&#xD;
          -  Patients who have any debilitating medical or psychiatric illness that would preclude&#xD;
             their giving informed consent or their receiving optimal treatment and follow up.&#xD;
&#xD;
          -  Uncontrolled viral, bacterial, or fungal infections (HIV infection permitted if viral&#xD;
             load undetectable)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>73 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amy DeZern, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Sidney Kimmel Comprehensive Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin/Children's Hospital of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <results_first_submitted>December 13, 2022</results_first_submitted>
  <results_first_submitted_qc>March 8, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 10, 2023</results_first_posted>
  <last_update_submitted>March 8, 2023</last_update_submitted>
  <last_update_submitted_qc>March 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>bone marrow transplant</keyword>
  <keyword>thymoglobulin</keyword>
  <keyword>cyclophosphamide</keyword>
  <keyword>fludarabine</keyword>
  <keyword>tacrolimus</keyword>
  <keyword>Mycophenolic Acid Mofetil</keyword>
  <keyword>chemotherapy</keyword>
  <keyword>GVHD</keyword>
  <keyword>haploidentical</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Anemia, Aplastic</mesh_term>
    <mesh_term>Bone Marrow Failure Disorders</mesh_term>
    <mesh_term>Pancytopenia</mesh_term>
    <mesh_term>Hemoglobinuria, Paroxysmal</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
    <mesh_term>Thymoglobulin</mesh_term>
  </intervention_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>February 11, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT02224872/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Bone Marrow Transplant</title>
          <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bone Marrow Transplant</title>
          <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </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>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30" lower_limit="5" upper_limit="69"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </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="1"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?</title>
        <description>Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?</title>
          <description>Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients That Have Survived at One Year</title>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients That Have Survived at One Year</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant</title>
        <description>Donor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with &gt;5% donor chimerism around day 60 will be considered as having engrafted.</description>
        <time_frame>60 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant</title>
          <description>Donor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with &gt;5% donor chimerism around day 60 will be considered as having engrafted.</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant</title>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </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 With Major Toxicities Related to Transplant</title>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Major Toxicities Related to Transplant</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </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 Patients That Expired Due to Transplant Related Mortality</title>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients That Expired Due to Transplant Related Mortality</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </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 Patients With Primary or Secondary Graft Failure Following Transplant</title>
        <description>Graft failure: &lt; 5% donor chimerism in blood and/or bone marrow on ~Day 30 or after and on all subsequent measurements.&#xD;
Primary graft failure: &lt; 5% donor chimerism in blood and/or bone marrow by ~ Day 56 Secondary graft failure: achievement of &gt; 5% donor chimerism, followed by sustained &lt;5% donor chimerism in blood and/or bone marrow.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Primary or Secondary Graft Failure Following Transplant</title>
          <description>Graft failure: &lt; 5% donor chimerism in blood and/or bone marrow on ~Day 30 or after and on all subsequent measurements.&#xD;
Primary graft failure: &lt; 5% donor chimerism in blood and/or bone marrow by ~ Day 56 Secondary graft failure: achievement of &gt; 5% donor chimerism, followed by sustained &lt;5% donor chimerism in blood and/or bone marrow.</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Grade II-IV or Grade III-IV Acute GVHD</title>
        <description>Participants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Grade II-IV or Grade III-IV Acute GVHD</title>
          <description>Participants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Chronic GVHD at One Year</title>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Chronic GVHD at One Year</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant</title>
        <description>CBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC &gt; 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant</title>
          <description>CBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC &gt; 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential.</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.85" lower_limit="14" upper_limit="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants That Were GVHD Free, Relapse Free Survival (GRFS)</title>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Transplant</title>
            <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
          </group>
        </group_list>
        <measure>
          <title>Participants That Were GVHD Free, Relapse Free Survival (GRFS)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Bone Marrow Transplant</title>
          <description>Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35&#xD;
Bone marrow transplant: Day 0&#xD;
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7&#xD;
Fludarabine: 30 mg/M2 IV on days -6 to -2&#xD;
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4&#xD;
TBI: 200 cGy on day -1&#xD;
Mesna: 40 mg/kg IV on days 3, 4&#xD;
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present&#xD;
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35</description>
        </group>
      </group_list>
      <serious_events>
        <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="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Persistent Fevers</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>dysuria/hematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Respiratory Distress Syndrom</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Acute Hypoxic Respiratory Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Intracranial Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Retroperitoneal Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hemorrhagic Shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Amy DeZern</name_or_title>
      <organization>Johns Hopkins University</organization>
      <phone>4105027208</phone>
      <email>Adezern1@jhmi.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/NCT02224872
org study id: J1424
secondary id: IRB00031590
nct id: NCT02224872
lead sponsor: 
has dmc: Yes
Our primary objective is to determine if it is feasible for SAA patients to be transplanted
      using non-myeloablative conditioning and post transplantation cyclophosphamide with partially
      HLA-mismatched donors.
This research is being done to find out if bone marrow transplantation (BMT) followed by
      chemotherapy will help people with aplastic anemia who have failed other treatments.

      You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow.
      Your disease has come back or not responded after receiving one or more immunosuppressive
      treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been
      used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD)
      and graft failure have limited the survival for those people.

      A small study done at Johns Hopkins has shown that in subjects with other diseases (blood
      cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects
      had complications of GVHD and engraftment failure.

      People with aplastic anemia who have refractory disease (not responding to standard
      treatment) may join.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?
time frame: 1 year
description: Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).
measure: Number of Patients That Have Survived at One Year
time frame: 1 year
measure: Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant
time frame: 60 days
description: Donor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with >5% donor chimerism around day 60 will be considered as having engrafted.
measure: Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant
time frame: 1 year
measure: Number of Participants With Major Toxicities Related to Transplant
time frame: 1 year
measure: Number of Patients That Expired Due to Transplant Related Mortality
time frame: 1 year
measure: Number of Patients With Primary or Secondary Graft Failure Following Transplant
time frame: 1 year
description: Graft failure: < 5% donor chimerism in blood and/or bone marrow on ~Day 30 or after and on all subsequent measurements.
Primary graft failure: < 5% donor chimerism in blood and/or bone marrow by ~ Day 56 Secondary graft failure: achievement of > 5% donor chimerism, followed by sustained <5% donor chimerism in blood and/or bone marrow.
measure: Number of Participants With Grade II-IV or Grade III-IV Acute GVHD
time frame: 1 year
description: Participants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement
measure: Participants With Chronic GVHD at One Year
time frame: 1 year
measure: Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant
time frame: 1 year
description: CBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC > 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential.
measure: Participants That Were GVHD Free, Relapse Free Survival (GRFS)
time frame: 1 year
arm group label: Bone marrow transplant
arm group type: Experimental
description: Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
intervention type: Procedure
intervention name: Bone marrow transplant
description: Day 0
arm group label: Bone marrow transplant
intervention type: Drug
intervention name: Thymoglobulin
description: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
arm group label: Bone marrow transplant
intervention type: Drug
intervention name: Fludarabine
description: 30 mg/M2 IV on days -6 to -2
arm group label: Bone marrow transplant
intervention type: Drug
intervention name: Cyclophosphamide
description: 14.5 mg/kg IV on days -6, -5, 3, 4
arm group label: Bone marrow transplant
other name: CTX
intervention type: Radiation
intervention name: TBI
description: 200 cGy on day -1
arm group label: Bone marrow transplant
intervention type: Drug
intervention name: Mesna
description: 40 mg/kg IV on days 3, 4
arm group label: Bone marrow transplant
intervention type: Drug
intervention name: Tacrolimus
description: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
arm group label: Bone marrow transplant
intervention type: Drug
intervention name: Mycophenolic acid mofetil
description: 15 mg/kg PO/IV TID beginning on day 5 through day 35
arm group label: Bone marrow transplant
other name: MMF
criteria: 
gender: All
minimum age: N/A
maximum age: 73 Years
healthy volunteers: No
last name: Amy DeZern, MD
role: Principal Investigator
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia
mesh term: Anemia, Aplastic
mesh term: Bone Marrow Failure Disorders
mesh term: Pancytopenia
mesh term: Hemoglobinuria, Paroxysmal
mesh term: Syndrome
mesh term: Mycophenolic Acid
mesh term: Cyclophosphamide
mesh term: Fludarabine
mesh term: Tacrolimus
mesh term: Thymoglobulin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 