<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/NCT02206035</url>
  </required_header>
  <id_info>
    <org_study_id>PRO00023000</org_study_id>
    <nct_id>NCT02206035</nct_id>
  </id_info>
  <brief_title>A Study of Tacrolimus/Methotrexate and Tocilizumab to Prevent Acute Graft-Versus-Host Disease (AGVD) After Allogeneic Hematopoietic Stem Cell Transplant</brief_title>
  <official_title>Phase II Open-Label Trial of Tacrolimus/Methotrexate and Tocilizumab for the Prevention of Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>William R. Drobyski, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical College of Wisconsin</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II open label trial designed to evaluate the efficacy of Tac/MTX/Toc in&#xD;
      preventing graft versus host disease (GVHD). Outcomes of patients on this clinical trial will&#xD;
      be compared to those of contemporary controls from the CIBMTR.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase II open label trial designed to evaluate the efficacy of Tacrolimus (Tac),&#xD;
      Methotrexate (MTX) and Tocilizumab (Toc) (combined Tac/MTX/Toc) in preventing graft versus&#xD;
      host disease (GVHD) after allogeneic hematopoietic stem cell transplantation compared to a&#xD;
      contemporary control cohort selected from the Center for International Bone Marrow Transplant&#xD;
      Research (CIBMTR) that is treated with standard methotrexate and tacrolimus for GVHD&#xD;
      prevention. The control group of patients will satisfy similar eligibility requirements as&#xD;
      the patients enrolled in the clinical trial and they will be matched for relevant clinical&#xD;
      variables (age, sex, conditioning regimen, disease, graft source, etc).&#xD;
&#xD;
      Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines&#xD;
      at doses to maintain therapeutic levels and continued until at least Day 90 post transplant.&#xD;
      Methotrexate will be dosed at 15 mg/m^2 Day +1 and 10mg/m^2 Days +3, +6 and +11. Tocilizumab&#xD;
      will be administered intravenously at a dose of 8 mg/kg at Day -1.&#xD;
&#xD;
      Ancillary Study:&#xD;
&#xD;
      The ancillary study will evaluate whether tocilizumab is effective at positively impacting&#xD;
      mood, fatigue, sleep, and pain in a group of individuals undergoing allogeneic hematopoietic&#xD;
      stem cell transplantation as compared to individuals not receiving tocilizumab. We will also&#xD;
      assess whether tocilizumab alters gene expression and Rap1 prenylation in a manner that may&#xD;
      reduce further progression or relapse of cancer after transplant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">September 2018</completion_date>
  <primary_completion_date type="Actual">September 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD)</measure>
    <time_frame>Day 180</time_frame>
    <description>This measure is the number of subjects who did not experience grade II-IV aGVHD at or before day 180 comparing recipients of tacrolimus (Tac), methotrexate (MTX), and tocilizumab (Toc) to a contemporary control population abstracted from a database maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR). The staging of aGVHD was according to the criteria of Przepiorka, et al., 1995 which assigns a score to the clinical status of multiple organ systems aggregated to determine the clinical stage. A higher stage indicates more severe aGVHD symptoms and poorer clinical outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument</measure>
    <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
    <description>The measure of depressive symptoms will be determined from the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. The IDAS contains 10 specific symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions (see Watson, 2007). The General Depression subscale of the IDAS and includes a subset of 20 five-item Likert-style questions (1= &quot;Not at All&quot; to 5-= &quot;Extremely&quot;) with a scoring range of 20-100. Higher scores indicate more severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument</measure>
    <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
    <description>Levels of anxiety symptoms will be measured using the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. (see Watson, 2007). Anxiety will be assessed combining two domain categories of the IDAS (panic and traumatic intrusions). There are seven 5-item, Likert-style questions responding symptom severity &quot;during the past 2 weeks, including today ...&quot; ranging from 'Not at all' to 'Extremely.' Scores range from 0 to 28 with higher scores indicating worse symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument</measure>
    <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
    <description>Levels of fatigue symptoms will be measured using the Fatigue Symptom Inventory instrument. The FSI comprises 13 eleven-item Likert-style questions ranging from 0 = &quot;Not at all fatigued&quot; to 10 -&quot;Extreme fatigue&quot;. The FSI score is the average of the individual question scores. The range of scores is 0 to 10 with higher scores indicate greater fatigue (Hann, 1998).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument</measure>
    <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
    <description>Levels of sleep symptoms will be measured using the Pittsburgh Sleep Quality Index instrument. The PSQI contains 19 four-item Likert-style questions conducted over a 30-day period and 5 questions rated by the bed partner or roommate. Responses range from 0 = Not in the past month to 3 = Three or more times a week. The bed partner/roommate questions were not assessed. The 19 self-rated questions are grouped into seven component domains including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. See Buysse (1989), for the scoring schema of the component domains. The PSQI score is the sum of the seven component scores and ranges from 0 to 21. Higher scores indicate poorer sleep quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)</measure>
    <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
    <description>Levels of interference in activities due to pain symptoms will be measured using the Brief Pain Inventory (BPI) instrument. The BPI Interference scale is a mean of 7 eleven-item Likert-style questions with a range of 0-10 (0 = Does not interfere to 10 = Completely interferes). Higher scores indicate greater interference in daily activities due to pain symptoms (see Cleeland 1994).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Hematopoietic Stem Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.</description>
    <arm_group_label>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</arm_group_label>
    <other_name>fujimycin</other_name>
    <other_name>FK506</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.</description>
    <arm_group_label>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</arm_group_label>
    <other_name>Trexall</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab</intervention_name>
    <description>Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
    <arm_group_label>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</arm_group_label>
    <other_name>Actemra</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 years&#xD;
&#xD;
          2. Patients with acute leukemia, chronic myelogenous leukemia, myeloproliferative disease&#xD;
             and myelodysplasia with less than 5% of blasts in the bone marrow&#xD;
&#xD;
          3. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, Non-Hodgkin&#xD;
             Lymphoma or Hodgkin Disease with chemosensitive disease at time of transplant&#xD;
&#xD;
          4. Planned conditioning regimens including combination of busulfan and fludarabine or&#xD;
             busulfan and cyclophosphamide&#xD;
&#xD;
          5. Transplantation with T-cell-replete grafts&#xD;
&#xD;
          6. Bone marrow or mobilized peripheral blood cell grafts&#xD;
&#xD;
          7. Patients must have either a sibling donor (6/6 match at human leukocyte antigens&#xD;
             (HLA-A, -B and -DRB1) or a unrelated donor (8/8 match at HLA-A, -B, -C and -DRB1)&#xD;
&#xD;
          8. Cardiac function: Ejection fraction at rest &gt;45% for myeloablative conditioning or&#xD;
             &gt;40% for reduced intensity conditioning&#xD;
&#xD;
          9. Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault&#xD;
             formula and actual body weight)&#xD;
&#xD;
         10. Pulmonary function: Diffusing Capacity of Lung for Carbon Monoxide (DLCO) ≥40%&#xD;
             (adjusted for hemoglobin) and FEV1≥50%&#xD;
&#xD;
         11. Liver function: total bilirubin &lt; 1.5 x the upper limit of normal and alanine&#xD;
             aminotransferase (ALT) / aspartate aminotransferase (AST) &lt; 2.5x the upper normal&#xD;
             limit&#xD;
&#xD;
         12. Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior allogeneic hematopoietic cell transplant (HCT)&#xD;
&#xD;
          2. Karnofsky Performance Score &lt;70%&#xD;
&#xD;
          3. Patients with uncontrolled bacterial, viral or fungal infections (currently taking&#xD;
             medication and with progression of infectious disease or no clinical improvement) at&#xD;
             time of enrollment&#xD;
&#xD;
          4. Prior intolerance or allergy to Tocilizumab&#xD;
&#xD;
          5. Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal&#xD;
             antibody at time of conditioning regimen&#xD;
&#xD;
          6. History of diverticulitis, Crohn's disease or ulcerative colitis&#xD;
&#xD;
          7. History of demyelinating disorder&#xD;
&#xD;
          8. Pregnant and lactating women&#xD;
&#xD;
          9. Patients with a history of rheumatologic disorders who have previously received&#xD;
             Tocilizumab&#xD;
&#xD;
        Eligibility for the Control Arm&#xD;
&#xD;
        Patients in the control arm will be identified from patients reported to the CIBMTR from&#xD;
        U.S centers. Control patients will be required to satisfy similar eligibility requirements&#xD;
        as patients being enrolled in the clinical trial. Patients will need to fulfill the same&#xD;
        inclusion criteria for the clinical trial according to Section 2.4.1, plus the following:&#xD;
&#xD;
          1. Receive Tac/MTX as the sole GVHD prophylaxis approach&#xD;
&#xD;
          2. Receive the same regimens as specified in Table 2.5&#xD;
&#xD;
          3. Year of transplant from 2010 to 2013&#xD;
&#xD;
        Exclusion criteria for the controls:&#xD;
&#xD;
        1. Karnofsky Performance Score &lt; 70%&#xD;
&#xD;
        Data for all eligible patients will be used to constitute the control database for this&#xD;
        study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William Drobyski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marcelo Pasquini, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jennifer Knight, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <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>Watson D, O'Hara MW, Simms LJ, Kotov R, Chmielewski M, McDade-Montez EA, Gamez W, Stuart S. Development and validation of the Inventory of Depression and Anxiety Symptoms (IDAS). Psychol Assess. 2007 Sep;19(3):253-68. doi: 10.1037/1040-3590.19.3.253.</citation>
    <PMID>17845118</PMID>
  </reference>
  <reference>
    <citation>D'Souza A, Lee S, Zhu X, Pasquini M. Current Use and Trends in Hematopoietic Cell Transplantation in the United States. Biol Blood Marrow Transplant. 2017 Sep;23(9):1417-1421. doi: 10.1016/j.bbmt.2017.05.035. Epub 2017 Jun 9.</citation>
    <PMID>28606646</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>
  <reference>
    <citation>Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.</citation>
    <PMID>25529383</PMID>
  </reference>
  <reference>
    <citation>Hann DM, Jacobsen PB, Azzarello LM, Martin SC, Curran SL, Fields KK, Greenberg H, Lyman G. Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory. Qual Life Res. 1998 May;7(4):301-10. doi: 10.1023/a:1024929829627.</citation>
    <PMID>9610214</PMID>
  </reference>
  <reference>
    <citation>Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.</citation>
    <PMID>2748771</PMID>
  </reference>
  <reference>
    <citation>Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.</citation>
    <PMID>8080219</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <results_first_submitted>December 19, 2022</results_first_submitted>
  <results_first_submitted_qc>February 10, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 9, 2023</results_first_posted>
  <last_update_submitted>February 10, 2023</last_update_submitted>
  <last_update_submitted_qc>February 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 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>William R. Drobyski, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <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>Methotrexate</mesh_term>
    <mesh_term>Tacrolimus</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>November 12, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/35/NCT02206035/Prot_SAP_002.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>January 28, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/35/NCT02206035/ICF_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The populations used for historical controls were not recruited by theses investigators. To obtain matched controls, the number of records analyzed exceeds the number recruited locally for the interventional arm.&#xD;
This investigation was conducted jointly by two research teams investigating the clinical effects, and the other investigating behavioral effects.. Each investigational team selected a population of matched historic controls appropriate to its outcome measures.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
          <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m^2 Day +1 and 10mg/m^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m^2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
        </group>
        <group group_id="P2">
          <title>Historical Control Arm (Primary Outcome Measure)</title>
          <description>This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017. (n=130)&#xD;
Race and ethnicity information was not collected for this control population.</description>
        </group>
        <group group_id="P3">
          <title>Historical Control Arm (Secondary Outcome Measures)</title>
          <description>This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant; BCNU/carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning; total body irradiation; anti-thymocyte globulin, sirolimus; cord blood transplant; or cyclosporine/mycophenolate mofetil prophylaxis for graft versus host disease were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="130"/>
                <participants group_id="P3" count="204"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="130"/>
                <participants group_id="P3" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="175"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="175"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
          <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m^2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
        </group>
        <group group_id="B2">
          <title>Historical Control Arm (Primary Outcome Measure)</title>
          <description>This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017. (n=130)&#xD;
Race and ethnicity information was not collected for this control population.</description>
        </group>
        <group group_id="B3">
          <title>Historical Control Arm (Secondary Outcome Measures)</title>
          <description>This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant; BCNU/carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning; total body irradiation; anti-thymocyte globulin; sirolimus; cord blood transplant; or cyclosporine/mycophenolate mofetil prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).</description>
        </group>
        <group group_id="B4">
          <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="35"/>
            <count group_id="B2" value="130"/>
            <count group_id="B3" value="29"/>
            <count group_id="B4" value="194"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="130"/>
                    <count group_id="B3" value="29"/>
                    <count group_id="B4" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66" lower_limit="22" upper_limit="76"/>
                    <measurement group_id="B2" value="64" lower_limit="23" upper_limit="74"/>
                    <measurement group_id="B3" value="54" lower_limit="44" upper_limit="64"/>
                    <measurement group_id="B4" value="62" lower_limit="22" upper_limit="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>Gender demographics was not collected for the Historical Control Arm (Primary Outcome Measure) population.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Known Gender</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="29"/>
                    <count group_id="B4" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B3" value="20"/>
                    <measurement group_id="B4" value="42"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="130"/>
                    <count group_id="B3" value="29"/>
                    <count group_id="B4" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </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="28"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="24"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="130"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="140"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="130"/>
                    <count group_id="B3" value="29"/>
                    <count group_id="B4" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="130"/>
                    <measurement group_id="B3" value="29"/>
                    <measurement group_id="B4" value="194"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD)</title>
        <description>This measure is the number of subjects who did not experience grade II-IV aGVHD at or before day 180 comparing recipients of tacrolimus (Tac), methotrexate (MTX), and tocilizumab (Toc) to a contemporary control population abstracted from a database maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR). The staging of aGVHD was according to the criteria of Przepiorka, et al., 1995 which assigns a score to the clinical status of multiple organ systems aggregated to determine the clinical stage. A higher stage indicates more severe aGVHD symptoms and poorer clinical outcome.</description>
        <time_frame>Day 180</time_frame>
        <population>The Historical Control Arm (Secondary Outcome Measures) cohort was included in this study for comparison of the behavioral results (Outcome Measures 2-6). The occurrence of aGVHD was not collected for this population. The Historical Control Arm (Secondary Outcome Measures) cohort has no clinical outcome for comparison and is not included in the analysis of this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
            <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m^2 Day +1 and 10mg/m^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m^2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
          </group>
          <group group_id="O2">
            <title>Historical Control Arm (Primary Outcome Measure)</title>
            <description>This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)&#xD;
Race and ethnicity information was not collected for this control population.</description>
          </group>
          <group group_id="O3">
            <title>Historical Control Arm (Secondary Outcome Measures)</title>
            <description>This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD)</title>
          <description>This measure is the number of subjects who did not experience grade II-IV aGVHD at or before day 180 comparing recipients of tacrolimus (Tac), methotrexate (MTX), and tocilizumab (Toc) to a contemporary control population abstracted from a database maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR). The staging of aGVHD was according to the criteria of Przepiorka, et al., 1995 which assigns a score to the clinical status of multiple organ systems aggregated to determine the clinical stage. A higher stage indicates more severe aGVHD symptoms and poorer clinical outcome.</description>
          <population>The Historical Control Arm (Secondary Outcome Measures) cohort was included in this study for comparison of the behavioral results (Outcome Measures 2-6). The occurrence of aGVHD was not collected for this population. The Historical Control Arm (Secondary Outcome Measures) cohort has no clinical outcome for comparison and is not included in the analysis of this outcome measure.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument</title>
        <description>The measure of depressive symptoms will be determined from the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. The IDAS contains 10 specific symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions (see Watson, 2007). The General Depression subscale of the IDAS and includes a subset of 20 five-item Likert-style questions (1= &quot;Not at All&quot; to 5-= &quot;Extremely&quot;) with a scoring range of 20-100. Higher scores indicate more severe symptoms.</description>
        <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
        <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
            <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
          </group>
          <group group_id="O2">
            <title>Historical Control Arm (Primary Outcome Measure)</title>
            <description>This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)&#xD;
Race and ethnicity information was not collected for this control population.</description>
          </group>
          <group group_id="O3">
            <title>Historical Control Arm (Secondary Outcome Measures)</title>
            <description>This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument</title>
          <description>The measure of depressive symptoms will be determined from the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. The IDAS contains 10 specific symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions (see Watson, 2007). The General Depression subscale of the IDAS and includes a subset of 20 five-item Likert-style questions (1= &quot;Not at All&quot; to 5-= &quot;Extremely&quot;) with a scoring range of 20-100. Higher scores indicate more severe symptoms.</description>
          <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.8" spread="8.8"/>
                    <measurement group_id="O3" value="38.9" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.7" spread="10.2"/>
                    <measurement group_id="O3" value="40.3" spread="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 100</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.5" spread="9.1"/>
                    <measurement group_id="O3" value="40.4" spread="14.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 180</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.6" spread="9.9"/>
                    <measurement group_id="O3" value="38.9" spread="13.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.95</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 28</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.26</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 100</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.63</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 180</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.76</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument</title>
        <description>Levels of anxiety symptoms will be measured using the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. (see Watson, 2007). Anxiety will be assessed combining two domain categories of the IDAS (panic and traumatic intrusions). There are seven 5-item, Likert-style questions responding symptom severity &quot;during the past 2 weeks, including today ...&quot; ranging from 'Not at all' to 'Extremely.' Scores range from 0 to 28 with higher scores indicating worse symptoms.</description>
        <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
        <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
            <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
          </group>
          <group group_id="O2">
            <title>Historical Control Arm (Primary Outcome Measure)</title>
            <description>This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)&#xD;
Race and ethnicity information was not collected for this control population.</description>
          </group>
          <group group_id="O3">
            <title>Historical Control Arm (Secondary Outcome Measures)</title>
            <description>This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument</title>
          <description>Levels of anxiety symptoms will be measured using the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. (see Watson, 2007). Anxiety will be assessed combining two domain categories of the IDAS (panic and traumatic intrusions). There are seven 5-item, Likert-style questions responding symptom severity &quot;during the past 2 weeks, including today ...&quot; ranging from 'Not at all' to 'Extremely.' Scores range from 0 to 28 with higher scores indicating worse symptoms.</description>
          <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0" spread="5.19"/>
                    <measurement group_id="O3" value="15.6" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.5" spread="4.3"/>
                    <measurement group_id="O3" value="16.9" spread="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 100</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.2" spread="6.0"/>
                    <measurement group_id="O3" value="17.4" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 180</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.6" spread="6.6"/>
                    <measurement group_id="O3" value="16.9" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.99</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 28</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.48</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.35</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 180</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.96</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument</title>
        <description>Levels of fatigue symptoms will be measured using the Fatigue Symptom Inventory instrument. The FSI comprises 13 eleven-item Likert-style questions ranging from 0 = &quot;Not at all fatigued&quot; to 10 -&quot;Extreme fatigue&quot;. The FSI score is the average of the individual question scores. The range of scores is 0 to 10 with higher scores indicate greater fatigue (Hann, 1998).</description>
        <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
        <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
            <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
          </group>
          <group group_id="O2">
            <title>Historical Control Arm (Primary Outcome Measure)</title>
            <description>This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)&#xD;
Race and ethnicity information was not collected for this control population.</description>
          </group>
          <group group_id="O3">
            <title>Historical Control Arm (Secondary Outcome Measures)</title>
            <description>This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument</title>
          <description>Levels of fatigue symptoms will be measured using the Fatigue Symptom Inventory instrument. The FSI comprises 13 eleven-item Likert-style questions ranging from 0 = &quot;Not at all fatigued&quot; to 10 -&quot;Extreme fatigue&quot;. The FSI score is the average of the individual question scores. The range of scores is 0 to 10 with higher scores indicate greater fatigue (Hann, 1998).</description>
          <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" spread="1.5"/>
                    <measurement group_id="O3" value="4.1" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="1.8"/>
                    <measurement group_id="O3" value="4.5" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 100</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7" spread="2.0"/>
                    <measurement group_id="O3" value="4.3" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 180</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="1.1"/>
                    <measurement group_id="O3" value="4.2" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 28</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.75</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 100</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.28</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 180</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.82</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument</title>
        <description>Levels of sleep symptoms will be measured using the Pittsburgh Sleep Quality Index instrument. The PSQI contains 19 four-item Likert-style questions conducted over a 30-day period and 5 questions rated by the bed partner or roommate. Responses range from 0 = Not in the past month to 3 = Three or more times a week. The bed partner/roommate questions were not assessed. The 19 self-rated questions are grouped into seven component domains including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. See Buysse (1989), for the scoring schema of the component domains. The PSQI score is the sum of the seven component scores and ranges from 0 to 21. Higher scores indicate poorer sleep quality.</description>
        <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
        <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
            <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
          </group>
          <group group_id="O2">
            <title>Historical Control Arm (Primary Outcome Measure)</title>
            <description>This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)&#xD;
Race and ethnicity information was not collected for this control population.</description>
          </group>
          <group group_id="O3">
            <title>Historical Control Arm (Secondary Outcome Measures)</title>
            <description>This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument</title>
          <description>Levels of sleep symptoms will be measured using the Pittsburgh Sleep Quality Index instrument. The PSQI contains 19 four-item Likert-style questions conducted over a 30-day period and 5 questions rated by the bed partner or roommate. Responses range from 0 = Not in the past month to 3 = Three or more times a week. The bed partner/roommate questions were not assessed. The 19 self-rated questions are grouped into seven component domains including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. See Buysse (1989), for the scoring schema of the component domains. The PSQI score is the sum of the seven component scores and ranges from 0 to 21. Higher scores indicate poorer sleep quality.</description>
          <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" spread="4.2"/>
                    <measurement group_id="O3" value="6.9" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" spread="4.4"/>
                    <measurement group_id="O3" value="7.8" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 100</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.9" spread="4.5"/>
                    <measurement group_id="O3" value="6.7" spread="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 180</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" spread="4.0"/>
                    <measurement group_id="O3" value="7.2" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.54</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 28</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.61</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 100</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.42</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 180</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.38</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)</title>
        <description>Levels of interference in activities due to pain symptoms will be measured using the Brief Pain Inventory (BPI) instrument. The BPI Interference scale is a mean of 7 eleven-item Likert-style questions with a range of 0-10 (0 = Does not interfere to 10 = Completely interferes). Higher scores indicate greater interference in daily activities due to pain symptoms (see Cleeland 1994).</description>
        <time_frame>Baseline, Day 28, Day 100 and Day 180</time_frame>
        <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
            <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.</description>
          </group>
          <group group_id="O2">
            <title>Historical Control Arm (Primary Outcome Measure)</title>
            <description>This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)&#xD;
Race and ethnicity information was not collected for this control population.</description>
          </group>
          <group group_id="O3">
            <title>Historical Control Arm (Secondary Outcome Measures)</title>
            <description>This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)</title>
          <description>Levels of interference in activities due to pain symptoms will be measured using the Brief Pain Inventory (BPI) instrument. The BPI Interference scale is a mean of 7 eleven-item Likert-style questions with a range of 0-10 (0 = Does not interfere to 10 = Completely interferes). Higher scores indicate greater interference in daily activities due to pain symptoms (see Cleeland 1994).</description>
          <population>The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure.&#xD;
Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="1.7"/>
                    <measurement group_id="O3" value="1.8" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="2.0"/>
                    <measurement group_id="O3" value="1.7" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 100</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" spread="1.8"/>
                    <measurement group_id="O3" value="2.2" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 180</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" spread="2.4"/>
                    <measurement group_id="O3" value="2.3" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.10</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 28</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.32</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 100</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.63</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison at Day 180</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.30</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <desc>Adverse events information was not collected for the historical control groups.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)</title>
          <description>Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1&#xD;
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.&#xD;
Methotrexate: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.&#xD;
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.&#xD;
The adverse events reported (serious and non-serious) include only those events experienced by subjects enrolled at the Medical College of Wisconsin site. Adverse events and serious adverse events were not abstracted from the databases for the two historical control populations.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE 4.03</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="13" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain - Cardiac</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </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="35"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE 4.03</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="35" subjects_at_risk="35"/>
              </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="23" subjects_affected="23" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="27" subjects_affected="27" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="35"/>
              </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="7" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="16" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>William Drobyski, MD</name_or_title>
      <organization>Froedtert and the Medical college of Wisconsin</organization>
      <phone>414-456-4941</phone>
      <email>wdrobysk@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/NCT02206035
org study id: PRO00023000
nct id: NCT02206035
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a phase II open label trial designed to evaluate the efficacy of Tac/MTX/Toc in
      preventing graft versus host disease (GVHD). Outcomes of patients on this clinical trial will
      be compared to those of contemporary controls from the CIBMTR.
This is a Phase II open label trial designed to evaluate the efficacy of Tacrolimus (Tac),
      Methotrexate (MTX) and Tocilizumab (Toc) (combined Tac/MTX/Toc) in preventing graft versus
      host disease (GVHD) after allogeneic hematopoietic stem cell transplantation compared to a
      contemporary control cohort selected from the Center for International Bone Marrow Transplant
      Research (CIBMTR) that is treated with standard methotrexate and tacrolimus for GVHD
      prevention. The control group of patients will satisfy similar eligibility requirements as
      the patients enrolled in the clinical trial and they will be matched for relevant clinical
      variables (age, sex, conditioning regimen, disease, graft source, etc).

      Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines
      at doses to maintain therapeutic levels and continued until at least Day 90 post transplant.
      Methotrexate will be dosed at 15 mg/m^2 Day +1 and 10mg/m^2 Days +3, +6 and +11. Tocilizumab
      will be administered intravenously at a dose of 8 mg/kg at Day -1.

      Ancillary Study:

      The ancillary study will evaluate whether tocilizumab is effective at positively impacting
      mood, fatigue, sleep, and pain in a group of individuals undergoing allogeneic hematopoietic
      stem cell transplantation as compared to individuals not receiving tocilizumab. We will also
      assess whether tocilizumab alters gene expression and Rap1 prenylation in a manner that may
      reduce further progression or relapse of cancer after transplant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD)
time frame: Day 180
description: This measure is the number of subjects who did not experience grade II-IV aGVHD at or before day 180 comparing recipients of tacrolimus (Tac), methotrexate (MTX), and tocilizumab (Toc) to a contemporary control population abstracted from a database maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR). The staging of aGVHD was according to the criteria of Przepiorka, et al., 1995 which assigns a score to the clinical status of multiple organ systems aggregated to determine the clinical stage. A higher stage indicates more severe aGVHD symptoms and poorer clinical outcome.
measure: Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
time frame: Baseline, Day 28, Day 100 and Day 180
description: The measure of depressive symptoms will be determined from the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. The IDAS contains 10 specific symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions (see Watson, 2007). The General Depression subscale of the IDAS and includes a subset of 20 five-item Likert-style questions (1= "Not at All" to 5-= "Extremely") with a scoring range of 20-100. Higher scores indicate more severe symptoms.
measure: Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
time frame: Baseline, Day 28, Day 100 and Day 180
description: Levels of anxiety symptoms will be measured using the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. (see Watson, 2007). Anxiety will be assessed combining two domain categories of the IDAS (panic and traumatic intrusions). There are seven 5-item, Likert-style questions responding symptom severity "during the past 2 weeks, including today ..." ranging from 'Not at all' to 'Extremely.' Scores range from 0 to 28 with higher scores indicating worse symptoms.
measure: Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument
time frame: Baseline, Day 28, Day 100 and Day 180
description: Levels of fatigue symptoms will be measured using the Fatigue Symptom Inventory instrument. The FSI comprises 13 eleven-item Likert-style questions ranging from 0 = "Not at all fatigued" to 10 -"Extreme fatigue". The FSI score is the average of the individual question scores. The range of scores is 0 to 10 with higher scores indicate greater fatigue (Hann, 1998).
measure: Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument
time frame: Baseline, Day 28, Day 100 and Day 180
description: Levels of sleep symptoms will be measured using the Pittsburgh Sleep Quality Index instrument. The PSQI contains 19 four-item Likert-style questions conducted over a 30-day period and 5 questions rated by the bed partner or roommate. Responses range from 0 = Not in the past month to 3 = Three or more times a week. The bed partner/roommate questions were not assessed. The 19 self-rated questions are grouped into seven component domains including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. See Buysse (1989), for the scoring schema of the component domains. The PSQI score is the sum of the seven component scores and ranges from 0 to 21. Higher scores indicate poorer sleep quality.
measure: Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)
time frame: Baseline, Day 28, Day 100 and Day 180
description: Levels of interference in activities due to pain symptoms will be measured using the Brief Pain Inventory (BPI) instrument. The BPI Interference scale is a mean of 7 eleven-item Likert-style questions with a range of 0-10 (0 = Does not interfere to 10 = Completely interferes). Higher scores indicate greater interference in daily activities due to pain symptoms (see Cleeland 1994).
arm group label: Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
arm group type: Experimental
description: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
intervention type: Drug
intervention name: Tacrolimus
description: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
arm group label: Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
other name: fujimycin
other name: FK506
intervention type: Drug
intervention name: Methotrexate
description: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.
arm group label: Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
other name: Trexall
intervention type: Drug
intervention name: Tocilizumab
description: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
arm group label: Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
other name: Actemra
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: William Drobyski, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
last name: Marcelo Pasquini, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
last name: Jennifer Knight, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
facility: 
country: United States
citation: Watson D, O'Hara MW, Simms LJ, Kotov R, Chmielewski M, McDade-Montez EA, Gamez W, Stuart S. Development and validation of the Inventory of Depression and Anxiety Symptoms (IDAS). Psychol Assess. 2007 Sep;19(3):253-68. doi: 10.1037/1040-3590.19.3.253.
PMID: 17845118
citation: D'Souza A, Lee S, Zhu X, Pasquini M. Current Use and Trends in Hematopoietic Cell Transplantation in the United States. Biol Blood Marrow Transplant. 2017 Sep;23(9):1417-1421. doi: 10.1016/j.bbmt.2017.05.035. Epub 2017 Jun 9.
PMID: 28606646
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: Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.
PMID: 25529383
citation: Hann DM, Jacobsen PB, Azzarello LM, Martin SC, Curran SL, Fields KK, Greenberg H, Lyman G. Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory. Qual Life Res. 1998 May;7(4):301-10. doi: 10.1023/a:1024929829627.
PMID: 9610214
citation: Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
PMID: 2748771
citation: Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.
PMID: 8080219
responsible party type: Sponsor-Investigator
investigator affiliation: Medical College of Wisconsin
investigator full name: William R. Drobyski, MD
investigator title: Professor
mesh term: Graft vs Host Disease
mesh term: Methotrexate
mesh term: Tacrolimus
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 