<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/NCT02215070</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00051736</org_study_id>
    <nct_id>NCT02215070</nct_id>
  </id_info>
  <brief_title>Pasireotide in Prevention of GI Toxicity</brief_title>
  <official_title>Prevention of Gastrointestinal Toxicity From Total Body Irradiation or High Dose Chemotherapy With Pasireotide</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Anthony Sung, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate if the drug, Pasireotide, is safe and effective in&#xD;
      reducing the gastrointestinal side effects of the drugs received to prepare for allogeneic&#xD;
      stem cell transplant. The study will also evaluate if Pasireotide is effective in reducing&#xD;
      acute and chronic Graft-versus-Host-Disease (GvHD) after transplant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study design will be a non-randomized phase II. Forty patients receiving an ablative&#xD;
      preparatory regimen will receive pasireotide subcutaneous (0.9 mg, b.i.d.) one day prior to&#xD;
      initiation of the preparatory regimen and continuing for eight days following the completion&#xD;
      of the preparatory regimen not to exceed 14 days total dosing. We select matched controls&#xD;
      from existing patients who did not take the drug to minimize the time it takes to complete&#xD;
      the trial.&#xD;
&#xD;
      Myeloablative preparatory regimens are defined as those including either TBI ≥ 1200 cGy or&#xD;
      busulfan ≥ 12.8 mg/kg. The most common regimens combine TBI with cyclophosphamide (TBI/Cy) or&#xD;
      busulfan with cyclophosphamide (Bu/Cy) (Appendix E). However, any regimen meeting the above&#xD;
      definition of myeloablative preparatory regimen may be used.&#xD;
&#xD;
      The study will collect data at screening, at baseline prior to initiation of the drug (day of&#xD;
      study drug start), transplant day 0, day +7, day +14 and weekly thereafter until day +100,&#xD;
      and on days +180, +270, and +365. The total days on pasireotide therapy will be recorded as&#xD;
      well as any SAE that is outside the expected for stem cell transplantation. We will also&#xD;
      follow the incidence and severity of acute and chronic GVHD.&#xD;
&#xD;
      At Duke only, a video capsule endoscopy will be performed in a subset of ten study patients&#xD;
      between transplant days +4 through +6. This substudy is descriptive in nature and only used&#xD;
      to collect a source of preliminary data that may suggest further study.&#xD;
&#xD;
      Patients must agree to participate in this portion of the study and will be asked to sign a&#xD;
      clinical consent for performance use of the video capsule endoscopy. Patients will be given&#xD;
      detailed instructions to prepare for the procedure. An investigator who is blinded to the&#xD;
      group allocation of the patients/volunteers separately will review the images obtained from&#xD;
      each of the capsule examinations. Images will be examined for evidence of the four following&#xD;
      types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis. Each of&#xD;
      these categories will be scored from 0-3 and summed to obtain an overall index that will&#xD;
      range from 0 (normal study) to 12 (severely abnormal in all categories).&#xD;
&#xD;
      Citrulline assay Measurement of citrulline concentration has been used as a marker for&#xD;
      cytotoxic treatment-induced intestinal damage and it is highly reproducible. The citrulline&#xD;
      concentration appears to be a quantitative parameter that is independent of the underlying&#xD;
      cause for epithelial cell loss and functions well in the post-SCT setting. Six mls of blood&#xD;
      will be collected in heparinized tubes on days 0, 7, and 14. Tubes will be centrifuged&#xD;
      according to manufacturer's instructions and the plasma will be collected and stored at -80C&#xD;
      until shipment to the laboratory performing the assay.&#xD;
&#xD;
      Calprotectin assay Calprotectin has been described as another biomarker of GI injury. During&#xD;
      radiation-induced inflammation, leucocytes infiltrate the mucosa and increase the level of&#xD;
      fecal calprotectin. At least 50 mg of stool specimen will be collected from patients on days&#xD;
      0, 7, and 14. Samples will be stored at -80C until shipment to the laboratory performing the&#xD;
      assay. Calprotectin will be measured with an ELISA kit (CALPRO, Oslo, Norway) in accordance&#xD;
      with the manufacturer's instructions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 21, 2015</start_date>
  <completion_date type="Actual">October 15, 2019</completion_date>
  <primary_completion_date type="Actual">February 28, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide</measure>
    <time_frame>30 Days</time_frame>
    <description>Number of participants who experience grades III-IV GI toxicity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Acute GVHD</measure>
    <time_frame>100 days</time_frame>
    <description>Number of participants who experience acute GVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Severity of Acute GVHD Compared to Historical Controls</measure>
    <time_frame>100 days</time_frame>
    <description>Assess maximum severity of acute GVHD scored as stage 1 (least severe) through stage 4 (most severe) using BMT CTN, 2013 standards</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Chronic GVHD Compared to Historical Controls</measure>
    <time_frame>1 year</time_frame>
    <description>Measure the number of participants who experience chronic GVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Severity of Chronic GVHD Compared to Historical Controls</measure>
    <time_frame>1 year</time_frame>
    <description>Assess maximum severity of chronic GVHD scored as none, mild, moderate or severe using 2014 NIH Consensus Criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Compared to Historical Controls</measure>
    <time_frame>1 year</time_frame>
    <description>Rate of overall survival of participants at one year post transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival Compared to Historical Controls</measure>
    <time_frame>1 year</time_frame>
    <description>Rate of disease free survival of participants at one year post transplant</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Citrulline and Fecal Calprotectin Levels Will be Measured</measure>
    <time_frame>100 days</time_frame>
    <description>Exploratory outcome-These levels will be evaluated as biomarkers of GI tract health and function in SCT patients and the correlation between these biomarkers and GI toxicity.</description>
  </other_outcome>
  <other_outcome>
    <measure>Evaluate GI Toxicity Assessment by Video Capsule Endoscopy.</measure>
    <time_frame>14 days</time_frame>
    <description>Exploratory outcome-Video capsule endoscopy will be performed in a subset of ten study participants on the last day study drug is administered. Images will be examined for evidence of the four following types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Hematological Malignancies</condition>
  <arm_group>
    <arm_group_label>Pasireotide + Preparatory Regimen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pasireotide</intervention_name>
    <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
    <arm_group_label>Pasireotide + Preparatory Regimen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years of age or older at the time of study enrollment.&#xD;
&#xD;
          -  Histologically confirmed diagnosis for which an allogeneic transplant is utilized.&#xD;
&#xD;
          -  Plan to receive an allogeneic transplant from a 4-6/6 single or dual umbilical cord&#xD;
             blood graft, or a 7-8/8 HLA-matched sibling or unrelated donor (High resolution HLA-A,&#xD;
             B, C, DRB1).&#xD;
&#xD;
          -  Meet standard criteria as defined by the institution for a myeloablative allogeneic&#xD;
             stem cell transplantation, with myeloablative defined as using conditioning regimens&#xD;
             containing:&#xD;
&#xD;
               -  TBI ≥ 1200 cGy, or&#xD;
&#xD;
               -  Busulfan ≥ 12.8mg/kg&#xD;
&#xD;
          -  Patient must have given written informed consent according to FDA guidelines.&#xD;
&#xD;
          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory&#xD;
             tests and other study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female patients who are pregnant or lactating, or are of childbearing potential (FCBP,&#xD;
             defined as all women physiologically capable of becoming pregnant) and not practicing&#xD;
             an effective method of contraception/birth control&#xD;
&#xD;
          -  FCBP must have a current negative serum pregnancy test prior to transplant per&#xD;
             institutional practice.&#xD;
&#xD;
          -  Use of an investigational drug within 1 month prior to dosing. Concurrent enrollment&#xD;
             on other clinical research studies that contain an interventional therapy is not&#xD;
             permitted while subjects are receiving pasireotide or within 5 half-lives of finishing&#xD;
             pasireotide. However, subjects may concurrently enroll in non-interventional studies&#xD;
             (e.g. biobanking, mobile health tracking).&#xD;
&#xD;
          -  Active CNS disease (related to primary malignancy) at the time of enrollment.&#xD;
&#xD;
          -  Patients with existing grade 2 toxicities, except as approved by the investigator.&#xD;
&#xD;
          -  Any of the following diseases or conditions:&#xD;
&#xD;
        Cardiac:&#xD;
&#xD;
          -  History of unexplained syncope or family history of idiopathic sudden death.&#xD;
&#xD;
          -  Sustained or clinically significant cardiac arrhythmias.&#xD;
&#xD;
          -  Risk factors for Torsades de Pointes such as:&#xD;
&#xD;
               -  Uncontrolled hypokalemia&#xD;
&#xD;
               -  Uncontrolled hypomagnesemia or hypermagnesemia&#xD;
&#xD;
               -  Cardiac failure (New York Heart Association Class II or higher)&#xD;
&#xD;
               -  Clinically significant/symptomatic bradycardia (HR &lt; 50), or high-grade AV block.&#xD;
&#xD;
               -  Known diagnosis of QT prolongation (QTc ≥ 470) or family history of long QT&#xD;
                  syndrome&#xD;
&#xD;
               -  Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused&#xD;
                  by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism&#xD;
                  or cardiac failure.&#xD;
&#xD;
               -  Concomitant medications known to prolong the QT interval during the same time as&#xD;
                  pasireotide is to be administered (unless approved by PI and QTc &lt; 470; standard&#xD;
                  transplant medications that are known to prolong the QT (e.g. azoles,&#xD;
                  ondansetron, etc.) are permitted but caution is advised and patients should be&#xD;
                  closely monitored).&#xD;
&#xD;
        Endocrine:&#xD;
&#xD;
          -  Uncontrolled diabetes at the time of cytoreduction. All patients with diabetes must be&#xD;
             optimized on their diabetes regimen prior to initiating pasireotide.&#xD;
&#xD;
             • If a patient is diabetic: uncontrolled diabetes as defined by HbA1c &gt; 8 per cent&#xD;
             despite adequate therapy&#xD;
&#xD;
          -  Patients who are not biochemically euthyroid. Patients with known history of&#xD;
             hypothyroidism are eligible if they are on adequate and stable replacement thyroid&#xD;
             hormone therapy for at least 3 months.&#xD;
&#xD;
          -  Known diagnosis of hypocortisolism&#xD;
&#xD;
          -  Known diagnosis of pituitary hormone deficiency.&#xD;
&#xD;
          -  Known hypersensitivity to somatostatin analogs or any component of the pasireotide LAR&#xD;
             or s.c. formulations.&#xD;
&#xD;
        Infectious:&#xD;
&#xD;
          -  Uncontrolled (not being treated) infections at the time of cytoreduction.&#xD;
&#xD;
          -  A positive HIV test result (ELISA and Western blot) or history of known HIV. An HIV&#xD;
             test will not be required; however, previous medical history will be reviewed.&#xD;
&#xD;
        Gastrointestinal:&#xD;
&#xD;
          -  Moderately impaired hepatic function (Child-Pugh B) or severe hepatic impairment&#xD;
             (Child-Pugh C)&#xD;
&#xD;
          -  Known gallbladder or bile duct disease, symptomatic cholelithiasis, acute or chronic&#xD;
             pancreatitis.&#xD;
&#xD;
          -  Known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by&#xD;
             specific therapeutic means.&#xD;
&#xD;
        Hematologic:&#xD;
&#xD;
          -  Abnormal coagulation (PT or aPTT &gt; 30% above normal limits).&#xD;
&#xD;
          -  Continuous anticoagulation therapy. Patients who were on anticoagulant therapy must&#xD;
             complete a washout period of at least 10 days and have confirmed normal coagulation&#xD;
             parameters before study inclusion.&#xD;
&#xD;
        Miscellaneous:&#xD;
&#xD;
          -  Major surgery/surgical therapy for any cause within 1 month prior to pasireotide&#xD;
             administration. Patients should have recovered and have a good clinical condition&#xD;
             before entering the study.&#xD;
&#xD;
          -  Any co-morbid condition which, in the view of the Principal Investigator, renders the&#xD;
             patient at high risk from treatment complications.&#xD;
&#xD;
        Patients with a history of non-compliance to medical regimens or who are considered&#xD;
        potentially unreliable or will not be able to complete the entire 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>Anthony Sung, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <results_first_submitted>February 27, 2020</results_first_submitted>
  <results_first_submitted_qc>February 27, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 11, 2020</results_first_posted>
  <last_update_submitted>October 19, 2021</last_update_submitted>
  <last_update_submitted_qc>October 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Anthony Sung, MD</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Allogeneic Stem Cell Transplantation</keyword>
  <keyword>Acute Myeloid Leukemia</keyword>
  <keyword>Acute Lymphoid Leukemia</keyword>
  <keyword>Acute Non-Lymphocytic Leukemia</keyword>
  <keyword>Myelodysplastic Syndrome</keyword>
  <keyword>Chronic Myeloid Leukemia</keyword>
  <keyword>Lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hematologic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pasireotide</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT02215070/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>5 enrolled participants screen failed, 5 withdrew, and 1 was withdrawn by physician decision.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pasireotide + Preparatory Regimen</title>
          <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
        </group>
        <group group_id="P2">
          <title>Historical Controls</title>
          <description>Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Pasireotide + Preparatory Regimen</title>
          <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
        </group>
        <group group_id="B2">
          <title>Historical Controls</title>
          <description>Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="26"/>
            <count group_id="B2" value="52"/>
            <count group_id="B3" value="78"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58" lower_limit="41" upper_limit="62"/>
                    <measurement group_id="B2" value="51" lower_limit="36" upper_limit="52"/>
                    <measurement group_id="B3" value="52" lower_limit="40" upper_limit="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Gender</title>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="72"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide</title>
        <description>Number of participants who experience grades III-IV GI toxicity</description>
        <time_frame>30 Days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pasireotide + Preparatory Regimen</title>
            <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide</title>
          <description>Number of participants who experience grades III-IV GI toxicity</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Acute GVHD</title>
        <description>Number of participants who experience acute GVHD</description>
        <time_frame>100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pasireotide + Preparatory Regimen</title>
            <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Acute GVHD</title>
          <description>Number of participants who experience acute GVHD</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Severity of Acute GVHD Compared to Historical Controls</title>
        <description>Assess maximum severity of acute GVHD scored as stage 1 (least severe) through stage 4 (most severe) using BMT CTN, 2013 standards</description>
        <time_frame>100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pasireotide + Preparatory Regimen</title>
            <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Severity of Acute GVHD Compared to Historical Controls</title>
          <description>Assess maximum severity of acute GVHD scored as stage 1 (least severe) through stage 4 (most severe) using BMT CTN, 2013 standards</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="1" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Chronic GVHD Compared to Historical Controls</title>
        <description>Measure the number of participants who experience chronic GVHD</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pasireotide + Preparatory Regimen</title>
            <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
          </group>
          <group group_id="O2">
            <title>Historical Controls</title>
            <description>Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Chronic GVHD Compared to Historical Controls</title>
          <description>Measure the number of participants who experience chronic GVHD</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.12</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Severity of Chronic GVHD Compared to Historical Controls</title>
        <description>Assess maximum severity of chronic GVHD scored as none, mild, moderate or severe using 2014 NIH Consensus Criteria</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pasireotide + Preparatory Regimen</title>
            <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
          </group>
          <group group_id="O2">
            <title>Historical Controls</title>
            <description>Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Severity of Chronic GVHD Compared to Historical Controls</title>
          <description>Assess maximum severity of chronic GVHD scored as none, mild, moderate or severe using 2014 NIH Consensus Criteria</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival Compared to Historical Controls</title>
        <description>Rate of overall survival of participants at one year post transplant</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pasireotide + Preparatory Regimen</title>
            <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
          </group>
          <group group_id="O2">
            <title>Historical Controls</title>
            <description>Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival Compared to Historical Controls</title>
          <description>Rate of overall survival of participants at one year post transplant</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63" lower_limit="47" upper_limit="86"/>
                    <measurement group_id="O2" value="82" lower_limit="72" upper_limit="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.006</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Free Survival Compared to Historical Controls</title>
        <description>Rate of disease free survival of participants at one year post transplant</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pasireotide + Preparatory Regimen</title>
            <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
          </group>
          <group group_id="O2">
            <title>Historical Controls</title>
            <description>Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Free Survival Compared to Historical Controls</title>
          <description>Rate of disease free survival of participants at one year post transplant</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40" lower_limit="25" upper_limit="65"/>
                    <measurement group_id="O2" value="78" lower_limit="68" upper_limit="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.002</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Citrulline and Fecal Calprotectin Levels Will be Measured</title>
        <description>Exploratory outcome-These levels will be evaluated as biomarkers of GI tract health and function in SCT patients and the correlation between these biomarkers and GI toxicity.</description>
        <time_frame>100 days</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Evaluate GI Toxicity Assessment by Video Capsule Endoscopy.</title>
        <description>Exploratory outcome-Video capsule endoscopy will be performed in a subset of ten study participants on the last day study drug is administered. Images will be examined for evidence of the four following types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis.</description>
        <time_frame>14 days</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were reported from the day Pasireotide started to day 30 after transplant (Day +30).</time_frame>
      <desc>Adverse event collection is not applicable for historical controls. Adverse events after Day 30 were not expected to be related to the intervention. However, HCT is a fraught process, with significant morbidity, and 10-20% of patients die from transplant-related complications. To determine if the study intervention would improve survival, overall survival was collected at year 1 (efficacy) and adverse events between Day 30-Year 1 were not collected.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pasireotide + Preparatory Regimen</title>
          <description>Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.</description>
        </group>
        <group group_id="E2">
          <title>Historical Controls</title>
          <description>Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Mobitz - Type II AV Block</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>VOD</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, specify; blood stream</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="26" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Afib</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sinus Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>2nd deg AVB</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pulmonary Edema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Eyes</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Floaters</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Mucositis</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bowel Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Myalgias</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Toe Trauma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>VOD</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>AST Elevation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>ALT Elevation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Alk Phos Elevation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bilirubin Elevation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Infusion Reaction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>HSV Reactivation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Otitis Media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Joint Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Catheter-Related Infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Thrush</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>UTI</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Viremia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Intracranial Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>PRES</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Inreased Creatinine</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bladder Spasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Prostatic Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>URI</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Acne Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Anthony Sung</name_or_title>
      <organization>Duke University</organization>
      <phone>919-668-1000</phone>
      <email>anthony.sung@duke.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/NCT02215070
org study id: Pro00051736
nct id: NCT02215070
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate if the drug, Pasireotide, is safe and effective in
      reducing the gastrointestinal side effects of the drugs received to prepare for allogeneic
      stem cell transplant. The study will also evaluate if Pasireotide is effective in reducing
      acute and chronic Graft-versus-Host-Disease (GvHD) after transplant.
The study design will be a non-randomized phase II. Forty patients receiving an ablative
      preparatory regimen will receive pasireotide subcutaneous (0.9 mg, b.i.d.) one day prior to
      initiation of the preparatory regimen and continuing for eight days following the completion
      of the preparatory regimen not to exceed 14 days total dosing. We select matched controls
      from existing patients who did not take the drug to minimize the time it takes to complete
      the trial.

      Myeloablative preparatory regimens are defined as those including either TBI ≥ 1200 cGy or
      busulfan ≥ 12.8 mg/kg. The most common regimens combine TBI with cyclophosphamide (TBI/Cy) or
      busulfan with cyclophosphamide (Bu/Cy) (Appendix E). However, any regimen meeting the above
      definition of myeloablative preparatory regimen may be used.

      The study will collect data at screening, at baseline prior to initiation of the drug (day of
      study drug start), transplant day 0, day +7, day +14 and weekly thereafter until day +100,
      and on days +180, +270, and +365. The total days on pasireotide therapy will be recorded as
      well as any SAE that is outside the expected for stem cell transplantation. We will also
      follow the incidence and severity of acute and chronic GVHD.

      At Duke only, a video capsule endoscopy will be performed in a subset of ten study patients
      between transplant days +4 through +6. This substudy is descriptive in nature and only used
      to collect a source of preliminary data that may suggest further study.

      Patients must agree to participate in this portion of the study and will be asked to sign a
      clinical consent for performance use of the video capsule endoscopy. Patients will be given
      detailed instructions to prepare for the procedure. An investigator who is blinded to the
      group allocation of the patients/volunteers separately will review the images obtained from
      each of the capsule examinations. Images will be examined for evidence of the four following
      types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis. Each of
      these categories will be scored from 0-3 and summed to obtain an overall index that will
      range from 0 (normal study) to 12 (severely abnormal in all categories).

      Citrulline assay Measurement of citrulline concentration has been used as a marker for
      cytotoxic treatment-induced intestinal damage and it is highly reproducible. The citrulline
      concentration appears to be a quantitative parameter that is independent of the underlying
      cause for epithelial cell loss and functions well in the post-SCT setting. Six mls of blood
      will be collected in heparinized tubes on days 0, 7, and 14. Tubes will be centrifuged
      according to manufacturer's instructions and the plasma will be collected and stored at -80C
      until shipment to the laboratory performing the assay.

      Calprotectin assay Calprotectin has been described as another biomarker of GI injury. During
      radiation-induced inflammation, leucocytes infiltrate the mucosa and increase the level of
      fecal calprotectin. At least 50 mg of stool specimen will be collected from patients on days
      0, 7, and 14. Samples will be stored at -80C until shipment to the laboratory performing the
      assay. Calprotectin will be measured with an ELISA kit (CALPRO, Oslo, Norway) in accordance
      with the manufacturer's instructions.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide
time frame: 30 Days
description: Number of participants who experience grades III-IV GI toxicity
measure: Percentage of Acute GVHD
time frame: 100 days
description: Number of participants who experience acute GVHD
measure: Maximum Severity of Acute GVHD Compared to Historical Controls
time frame: 100 days
description: Assess maximum severity of acute GVHD scored as stage 1 (least severe) through stage 4 (most severe) using BMT CTN, 2013 standards
measure: Incidence of Chronic GVHD Compared to Historical Controls
time frame: 1 year
description: Measure the number of participants who experience chronic GVHD
measure: Maximum Severity of Chronic GVHD Compared to Historical Controls
time frame: 1 year
description: Assess maximum severity of chronic GVHD scored as none, mild, moderate or severe using 2014 NIH Consensus Criteria
measure: Overall Survival Compared to Historical Controls
time frame: 1 year
description: Rate of overall survival of participants at one year post transplant
measure: Disease Free Survival Compared to Historical Controls
time frame: 1 year
description: Rate of disease free survival of participants at one year post transplant
measure: Citrulline and Fecal Calprotectin Levels Will be Measured
time frame: 100 days
description: Exploratory outcome-These levels will be evaluated as biomarkers of GI tract health and function in SCT patients and the correlation between these biomarkers and GI toxicity.
measure: Evaluate GI Toxicity Assessment by Video Capsule Endoscopy.
time frame: 14 days
description: Exploratory outcome-Video capsule endoscopy will be performed in a subset of ten study participants on the last day study drug is administered. Images will be examined for evidence of the four following types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis.
arm group label: Pasireotide + Preparatory Regimen
arm group type: Experimental
description: Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.
intervention type: Drug
intervention name: Pasireotide
description: Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.
arm group label: Pasireotide + Preparatory Regimen
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anthony Sung, MD
role: Principal Investigator
affiliation: Duke University
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Anthony Sung, MD
investigator title: Professor of Medicine
mesh term: Hematologic Neoplasms
mesh term: Pasireotide
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point of contact: 