<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/NCT01665677</url>
  </required_header>
  <id_info>
    <org_study_id>PRO00021090</org_study_id>
    <secondary_id>WVU 011012</secondary_id>
    <secondary_id>116837-IRG-09-061-01</secondary_id>
    <nct_id>NCT01665677</nct_id>
  </id_info>
  <brief_title>Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoietic Cell Transplantation</brief_title>
  <official_title>Phase II Study of Atorvastatin, Micro-dose Methotrexate and Tacrolimus Administered Only to Transplant Recipients for the Prophylaxis of Acute Graft-versus-host Disease Following Allogeneic Hematopoietic Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mehdi Hamadani</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>West Virginia University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical College of Wisconsin</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hematopoietic stem cell transplantation is a procedure in which a person receives blood&#xD;
      forming stem cells from a person called a &quot;donor.&quot; The stem cells can be obtained from the&#xD;
      hollow part of the hip bone or from blood.&#xD;
&#xD;
      A serious problem with this treatment is graft-versus-host disease (GVHD). This happens when&#xD;
      stem cells from the donor attack normal cells of the recipient. Currently, there is no&#xD;
      universal standard of care in the United States to prevent GVHD.&#xD;
&#xD;
      This study is being done to see if a medicine that is used to lower cholesterol can also help&#xD;
      in reducing GVHD.&#xD;
&#xD;
      Patients will receive atorvastatin daily by mouth starting 14 days before stem cell&#xD;
      transplant. They will continue to take atorvastatin until 180 days after transplant. This&#xD;
      medicine may be stopped earlier if there is a bad side effect or a severe GVHD. Patients will&#xD;
      also receive standard treatment to prevent GVHD. Patients will undergo many tests that are&#xD;
      standard for their treatment at West Virginia University (WVU), including blood tests to&#xD;
      check blood counts, kidney function and HIV status; blood test to check for pregnancy; Multi&#xD;
      Gated Acquisition Scan (MUGA scan)or echocardiogram to test heart function; lung function&#xD;
      testing; and bone marrow aspirate or biopsy. Patients will also have the option to provide&#xD;
      blood samples for optional research related to the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute graft-versus-host disease (GVHD) is one of the most frequent complications after&#xD;
      allogeneic hematopoietic stem cell transplantation (HSCT).(1) It develops in 30-75% of&#xD;
      recipients of allogeneic HSCT depending on the degree of histocompatibility between the donor&#xD;
      and the recipient, number of T-cells in the graft, recipient's age and GVHD prophylactic&#xD;
      regimen used. (2-4) Novel strategies designed to effectively prevent the development of this&#xD;
      life threatening complication of allogeneic transplantation are urgently needed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 20, 2014</start_date>
  <completion_date type="Actual">July 9, 2021</completion_date>
  <primary_completion_date type="Actual">July 9, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Matched Related Transplants Who Develop Grade II-IV Acute Graft Versus Host Disease (GVHD).</measure>
    <time_frame>Day 100</time_frame>
    <description>The number of subjects in the matched sibling cohort who develop grades II-IV acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched unrelated donors are not included in this analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Matched Unrelated Donors Transplants Who Develop Grade II-IV Acute GVHD.</measure>
    <time_frame>Day 100</time_frame>
    <description>The number of subjects in the matched unrelated donor cohort who develop grade II-IV acute GVHD. Acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched related donors are not included in this analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Matched Related Transplants Who Develop Grade II-IV Chronic GVHD.</measure>
    <time_frame>1 year</time_frame>
    <description>The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [&gt;15%] or esophageal dilation), liver (normal function to bilirubin or enzymes &gt;5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched unrelated donors are not included in this analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Matched Unrelated Donors Transplants Who Develop Grade II-IV Chronic GVHD.</measure>
    <time_frame>1 year</time_frame>
    <description>The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [&gt;15%] or esophageal dilation), liver (normal function to bilirubin or enzymes &gt;5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched related donors are not included.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">69</enrollment>
  <condition>Graft vs Host Disease</condition>
  <arm_group>
    <arm_group_label>Atorvastatin calcium (Lipitor)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Unrelated Donor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin calcium</intervention_name>
    <description>40 mg PO daily</description>
    <arm_group_label>Atorvastatin calcium (Lipitor)</arm_group_label>
    <arm_group_label>Unrelated Donor</arm_group_label>
    <other_name>Lipitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a history of a hematological malignancy or bone marrow failure syndrome&#xD;
             suitable for allogeneic stem cell transplantation in the opinion of treating&#xD;
             transplant physician.&#xD;
&#xD;
          -  Patients aged 18-75 years of age are eligible. Patients with age &gt; 18 and ≤ 50 years&#xD;
             will be eligible for myeloablative conditioning (MAC), while patients &gt; 50 years of&#xD;
             age, or those with previous history of autologous transplantation, high hematopoietic&#xD;
             cell transplant comorbidity index (HCT-CI) score (&gt;2), and baseline diagnosis of&#xD;
             hodgkin's lymphoma, chronic lymphocytic leukemia and follicular lymphoma will be&#xD;
             suitable for reduced intensity conditioning (RIC) transplantation (however intensity&#xD;
             of conditioning regimen will remain at the discretion of treating physician).&#xD;
&#xD;
          -  All patients must have at least one suitable human leukocyte antigen (HLA)-matched&#xD;
             sibling or unrelated donor according to transplant center's guidelines (for selection&#xD;
             of appropriate sibling donor).&#xD;
&#xD;
          -  Patient must provide informed consent.&#xD;
&#xD;
          -  Left ventricular ejection fraction ≥ 40%.&#xD;
&#xD;
          -  Bilirubin ≤ 2 x the upper limit of normal (ULN) and aspartate aminotransferase (AST),&#xD;
             and alanine aminotransferase (ALT) ≤ 3 x ULN; and absence of hepatic cirrhosis. For&#xD;
             patients with Gilbert's syndrome, bilirubin ≤ 3 x ULN is permitted.&#xD;
&#xD;
          -  Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal&#xD;
             calculated by Cockcroft-Gault equation.&#xD;
&#xD;
          -  Carbon monoxide diffusing capacity (DLCOcor) corrected for hemoglobin or forced&#xD;
             expiratory volume at one second (FEV1) or DL/VA ≥ 40% of predicted (a pulmonary&#xD;
             function test).&#xD;
&#xD;
          -  Karnofsky performance status &gt; 70.&#xD;
&#xD;
          -  A negative pregnancy test will be required for all women of child bearing potential.&#xD;
             Breast feeding is not permitted.&#xD;
&#xD;
          -  Patients with positive HIV serology are eligible.&#xD;
&#xD;
          -  Patients who have previously been taking atorvastatin or any other statin drug will be&#xD;
             eligible as long as there is no contraindication to switch to atorvastatin (40mg/day)&#xD;
             in the opinion of the treating physician.&#xD;
&#xD;
          -  Method of stem-cell collection from the sibling donor will be at the discretion of the&#xD;
             treating physician. Although it is anticipated that majority of sibling donors will&#xD;
             undergo Granulocyte colony-stimulating factor(G-CSF) induced stem cell mobilization;&#xD;
             however donors undergoing bone marrow harvest or stem cell mobilization with&#xD;
             experimental agents (e.g. plerixafor) will remain eligible for the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart&#xD;
             failure.&#xD;
&#xD;
          -  Evidence of active bacterial, viral or fungal infection at the time of transplant&#xD;
             conditioning.&#xD;
&#xD;
          -  History of intolerance or allergic reactions with atorvastatin will not be eligible.&#xD;
&#xD;
          -  Undergoing a T-cell depleted allogeneic transplantation&#xD;
&#xD;
          -  Receiving conditioning regimens containing anti-thymocyte globulin, and/or campath&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Craig, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>West Virginia University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mehdi Hamadani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>West Virginia University Hospitals Mary Babb Randolph Cancer Center</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Froedtert Hospital and the Medical College 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>
  <reference>
    <citation>Deeg HJ. How I treat refractory acute GVHD. Blood. 2007 May 15;109(10):4119-26. doi: 10.1182/blood-2006-12-041889. Epub 2007 Jan 18.</citation>
    <PMID>17234737</PMID>
  </reference>
  <reference>
    <citation>Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D, Fay JW, Nademanee A, Antin JH, Christiansen NP, van der Jagt R, Herzig RH, Litzow MR, Wolff SN, Longo WL, Petersen FB, Karanes C, Avalos B, Storb R, Buell DN, Maher RM, Fitzsimmons WE, Wingard JR. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998 Oct 1;92(7):2303-14.</citation>
    <PMID>9746768</PMID>
  </reference>
  <reference>
    <citation>Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM, Przepiorka D, Davies S, Petersen FB, Bartels P, Buell D, Fitzsimmons W, Anasetti C, Storb R, Ratanatharathorn V. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000 Sep 15;96(6):2062-8.</citation>
    <PMID>10979948</PMID>
  </reference>
  <reference>
    <citation>Antin JH, Kim HT, Cutler C, Ho VT, Lee SJ, Miklos DB, Hochberg EP, Wu CJ, Alyea EP, Soiffer RJ. Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood. 2003 Sep 1;102(5):1601-5. doi: 10.1182/blood-2003-02-0489. Epub 2003 May 1.</citation>
    <PMID>12730113</PMID>
  </reference>
  <reference>
    <citation>Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118. doi: 10.1146/annurev.pharmtox.45.120403.095748.</citation>
    <PMID>15822172</PMID>
  </reference>
  <reference>
    <citation>Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.</citation>
    <PMID>7581076</PMID>
  </reference>
  <results_reference>
    <citation>Kanate AS, Hari PN, Pasquini MC, Visotcky A, Ahn KW, Boyd J, Guru Murthy GS, Rizzo JD, Saber W, Drobyski W, Michaelis L, Atallah E, Carlson KS, D'Souza A, Fenske TS, Cumpston A, Bunner P, Craig M, Horowitz MM, Hamadani M. Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation. Biol Blood Marrow Transplant. 2017 Aug;23(8):1295-1302. doi: 10.1016/j.bbmt.2017.04.009. Epub 2017 Apr 12.</citation>
    <PMID>28412518</PMID>
  </results_reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2012</study_first_posted>
  <results_first_submitted>March 25, 2023</results_first_submitted>
  <results_first_submitted_qc>April 20, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 15, 2023</results_first_posted>
  <last_update_submitted>April 20, 2023</last_update_submitted>
  <last_update_submitted_qc>April 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Medical College of Wisconsin</investigator_affiliation>
    <investigator_full_name>Mehdi Hamadani</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Graft vs Host Disease</keyword>
  <keyword>GVHD</keyword>
  <keyword>Allogeneic hematopoietic stem cell transplantation</keyword>
  <keyword>HSCT</keyword>
  <keyword>Atorvastatin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atorvastatin</mesh_term>
    <mesh_term>Calcium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>July 3, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT01665677/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 20, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT01665677/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>75 subjects signed consent. Six did not meet eligibility criteria and were not treated.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Matched Related Donor</title>
          <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
        </group>
        <group group_id="P2">
          <title>Matched Unrelated Donor</title>
          <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Atorvastatin Calcium (Lipitor)</title>
          <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
        </group>
        <group group_id="B2">
          <title>Unrelated Donor</title>
          <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
            <count group_id="B2" value="39"/>
            <count group_id="B3" value="69"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </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="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Matched Related Transplants Who Develop Grade II-IV Acute Graft Versus Host Disease (GVHD).</title>
        <description>The number of subjects in the matched sibling cohort who develop grades II-IV acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched unrelated donors are not included in this analysis.</description>
        <time_frame>Day 100</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Matched Related Donor</title>
            <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
          </group>
        </group_list>
        <measure>
          <title>Matched Related Transplants Who Develop Grade II-IV Acute Graft Versus Host Disease (GVHD).</title>
          <description>The number of subjects in the matched sibling cohort who develop grades II-IV acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched unrelated donors are not included in this analysis.</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="30"/>
              </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>Primary</type>
        <title>Matched Unrelated Donors Transplants Who Develop Grade II-IV Acute GVHD.</title>
        <description>The number of subjects in the matched unrelated donor cohort who develop grade II-IV acute GVHD. Acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched related donors are not included in this analysis.</description>
        <time_frame>Day 100</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Matched Unrelated Donor</title>
            <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
          </group>
        </group_list>
        <measure>
          <title>Matched Unrelated Donors Transplants Who Develop Grade II-IV Acute GVHD.</title>
          <description>The number of subjects in the matched unrelated donor cohort who develop grade II-IV acute GVHD. Acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched related donors are not included in this analysis.</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="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Matched Related Transplants Who Develop Grade II-IV Chronic GVHD.</title>
        <description>The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [&gt;15%] or esophageal dilation), liver (normal function to bilirubin or enzymes &gt;5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched unrelated donors are not included in this analysis.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Matched Related Donor</title>
            <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
          </group>
        </group_list>
        <measure>
          <title>Matched Related Transplants Who Develop Grade II-IV Chronic GVHD.</title>
          <description>The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [&gt;15%] or esophageal dilation), liver (normal function to bilirubin or enzymes &gt;5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched unrelated donors are not included in this analysis.</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="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Matched Unrelated Donors Transplants Who Develop Grade II-IV Chronic GVHD.</title>
        <description>The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [&gt;15%] or esophageal dilation), liver (normal function to bilirubin or enzymes &gt;5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched related donors are not included.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Matched Unrelated Donor</title>
            <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
          </group>
        </group_list>
        <measure>
          <title>Matched Unrelated Donors Transplants Who Develop Grade II-IV Chronic GVHD.</title>
          <description>The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [&gt;15%] or esophageal dilation), liver (normal function to bilirubin or enzymes &gt;5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched related donors are not included.</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="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Atorvastatin Calcium (Lipitor)</title>
          <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
        </group>
        <group group_id="E2">
          <title>Unrelated Donor</title>
          <description>Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.&#xD;
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.&#xD;
Atorvastatin calcium: 40 mg PO daily</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCA 4.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE 4.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="13" subjects_at_risk="30"/>
                <counts group_id="E2" events="35" subjects_affected="23" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <description>Carotid artery disease</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vestibular disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Glaucoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <description>Neck lesion biopsy</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Multi-organ failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pollen allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Catheter related infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Endocarditis infective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hepatitis viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Scabies</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Small intestine infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Large intestine infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Multiple drug resistant infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Otitis externa</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Breast infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Injury, poisoning and procedural complications - Other, specify</sub_title>
                <description>Transfusion reaction</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT corrected interval prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dyslipidemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Ferritin increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Red blood cell count decreased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="30"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Chloride increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Blood urea nitrogen increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Total protein decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lactate dehydrogenase decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hematocrit decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypercholesterolemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Monocyte count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Monocyte count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Red blood cell count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Chloride decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Bicarbonate decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Blood Urea Nitrogen decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Eosinophils decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Anion gap high</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="30"/>
                <counts group_id="E2" events="14" subjects_affected="14" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="17" subjects_affected="17" subjects_at_risk="30"/>
                <counts group_id="E2" events="17" subjects_affected="17" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="30"/>
                <counts group_id="E2" events="15" subjects_affected="15" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="30"/>
                <counts group_id="E2" events="17" subjects_affected="17" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="30"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Obesity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Joint effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased lumbar spine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Drug-induced myopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Uterine polyps</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Renal calculi</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Erectile dysfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Premature menopause</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Adult respiratory distress syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Chronic occlusive pulmonary disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Sleep apnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Appendectomy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cholesystectomy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cardiac stent placed</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nissen fundoplication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Skin grafts trunk arm leg 100 cm^2 or less</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Inferior vena cava filter placed</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="30"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="39"/>
              </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>Dr. Medhi Hamadani</name_or_title>
      <organization>Medical College of Wisconsin</organization>
      <phone>414-805-6800</phone>
      <email>mhamadani@mcw.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/NCT01665677
org study id: PRO00021090
secondary id: WVU 011012
secondary id: 116837-IRG-09-061-01
nct id: NCT01665677
lead sponsor: 
collaborator: 
has dmc: Yes
Hematopoietic stem cell transplantation is a procedure in which a person receives blood
      forming stem cells from a person called a "donor." The stem cells can be obtained from the
      hollow part of the hip bone or from blood.

      A serious problem with this treatment is graft-versus-host disease (GVHD). This happens when
      stem cells from the donor attack normal cells of the recipient. Currently, there is no
      universal standard of care in the United States to prevent GVHD.

      This study is being done to see if a medicine that is used to lower cholesterol can also help
      in reducing GVHD.

      Patients will receive atorvastatin daily by mouth starting 14 days before stem cell
      transplant. They will continue to take atorvastatin until 180 days after transplant. This
      medicine may be stopped earlier if there is a bad side effect or a severe GVHD. Patients will
      also receive standard treatment to prevent GVHD. Patients will undergo many tests that are
      standard for their treatment at West Virginia University (WVU), including blood tests to
      check blood counts, kidney function and HIV status; blood test to check for pregnancy; Multi
      Gated Acquisition Scan (MUGA scan)or echocardiogram to test heart function; lung function
      testing; and bone marrow aspirate or biopsy. Patients will also have the option to provide
      blood samples for optional research related to the study.
Acute graft-versus-host disease (GVHD) is one of the most frequent complications after
      allogeneic hematopoietic stem cell transplantation (HSCT).(1) It develops in 30-75% of
      recipients of allogeneic HSCT depending on the degree of histocompatibility between the donor
      and the recipient, number of T-cells in the graft, recipient's age and GVHD prophylactic
      regimen used. (2-4) Novel strategies designed to effectively prevent the development of this
      life threatening complication of allogeneic transplantation are urgently needed.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Matched Related Transplants Who Develop Grade II-IV Acute Graft Versus Host Disease (GVHD).
time frame: Day 100
description: The number of subjects in the matched sibling cohort who develop grades II-IV acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched unrelated donors are not included in this analysis.
measure: Matched Unrelated Donors Transplants Who Develop Grade II-IV Acute GVHD.
time frame: Day 100
description: The number of subjects in the matched unrelated donor cohort who develop grade II-IV acute GVHD. Acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched related donors are not included in this analysis.
measure: Matched Related Transplants Who Develop Grade II-IV Chronic GVHD.
time frame: 1 year
description: The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [>15%] or esophageal dilation), liver (normal function to bilirubin or enzymes >5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched unrelated donors are not included in this analysis.
measure: Matched Unrelated Donors Transplants Who Develop Grade II-IV Chronic GVHD.
time frame: 1 year
description: The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [>15%] or esophageal dilation), liver (normal function to bilirubin or enzymes >5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched related donors are not included.
arm group label: Atorvastatin calcium (Lipitor)
arm group type: Experimental
description: Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.
arm group label: Unrelated Donor
arm group type: Experimental
description: Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning.
Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.
intervention type: Drug
intervention name: Atorvastatin calcium
description: 40 mg PO daily
arm group label: Atorvastatin calcium (Lipitor)
arm group label: Unrelated Donor
other name: Lipitor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Michael Craig, MD
role: Principal Investigator
affiliation: West Virginia University
last name: Mehdi Hamadani, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
facility: 
facility: 
country: United States
citation: Deeg HJ. How I treat refractory acute GVHD. Blood. 2007 May 15;109(10):4119-26. doi: 10.1182/blood-2006-12-041889. Epub 2007 Jan 18.
PMID: 17234737
citation: Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D, Fay JW, Nademanee A, Antin JH, Christiansen NP, van der Jagt R, Herzig RH, Litzow MR, Wolff SN, Longo WL, Petersen FB, Karanes C, Avalos B, Storb R, Buell DN, Maher RM, Fitzsimmons WE, Wingard JR. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998 Oct 1;92(7):2303-14.
PMID: 9746768
citation: Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM, Przepiorka D, Davies S, Petersen FB, Bartels P, Buell D, Fitzsimmons W, Anasetti C, Storb R, Ratanatharathorn V. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000 Sep 15;96(6):2062-8.
PMID: 10979948
citation: Antin JH, Kim HT, Cutler C, Ho VT, Lee SJ, Miklos DB, Hochberg EP, Wu CJ, Alyea EP, Soiffer RJ. Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood. 2003 Sep 1;102(5):1601-5. doi: 10.1182/blood-2003-02-0489. Epub 2003 May 1.
PMID: 12730113
citation: Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118. doi: 10.1146/annurev.pharmtox.45.120403.095748.
PMID: 15822172
citation: Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.
PMID: 7581076
citation: Kanate AS, Hari PN, Pasquini MC, Visotcky A, Ahn KW, Boyd J, Guru Murthy GS, Rizzo JD, Saber W, Drobyski W, Michaelis L, Atallah E, Carlson KS, D'Souza A, Fenske TS, Cumpston A, Bunner P, Craig M, Horowitz MM, Hamadani M. Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation. Biol Blood Marrow Transplant. 2017 Aug;23(8):1295-1302. doi: 10.1016/j.bbmt.2017.04.009. Epub 2017 Apr 12.
PMID: 28412518
responsible party type: Sponsor-Investigator
investigator affiliation: Medical College of Wisconsin
investigator full name: Mehdi Hamadani
investigator title: Professor
mesh term: Graft vs Host Disease
mesh term: Atorvastatin
mesh term: Calcium
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 