xml: <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/NCT06008808</url>
    </required_header>
    <id_info>
      <org_study_id>23-x287</org_study_id>
      <nct_id>NCT06008808</nct_id>
    </id_info>
    <brief_title>Ruxolitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation</brief_title>
    <official_title>An Open-Label Phase II Study of JAK Inhibitor Ruxolitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Washington University School of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Incyte Corporation</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Washington University School of Medicine</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Allogeneic hematopoietic cell transplantation (HCT) is one of the only curative intent&#xD;
        therapies available for hematologic malignancies. HLA-matched sibling donors have&#xD;
        historically offered the best clinical results but are unavailable for the majority of&#xD;
        patients, while most patients do have readily available haploidentical donors. One of the&#xD;
        risks of a haploidentical HCT is graft vs. host disease (GVHD), but it is difficult to reduce&#xD;
        the incidence of GVHD without compromising the graft vs. leukemia (GVL) effect.&#xD;
  &#xD;
        The hypothesis of this study is that JAK inhibition with haploidentical HCT may mitigate GVHD&#xD;
        and cytokine release syndrome while retaining the GVL effect and improving engraftment.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 31, 2023</start_date>
    <completion_date type="Anticipated">May 11, 2026</completion_date>
    <primary_completion_date type="Anticipated">February 9, 2026</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>Cumulative incidence of graft failure</measure>
      <time_frame>Day 35</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Cumulative incidence of grades III-IV acute GVHD by MAGIC criteria</measure>
      <time_frame>Day 100</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of grades II-IV acute GVHD by MAGIC criteria</measure>
      <time_frame>Day 100</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of patients who experience cytokine release syndrome (CRS)</measure>
      <time_frame>Through Day 8</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Treatment-related mortality</measure>
      <time_frame>Day 180</time_frame>
      <description>Defined as death resulting from a transplant procedure-related complication rather than from relapse of the underlying disease or an unrelated cause</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">49</enrollment>
    <condition>Graft Vs Host Disease</condition>
    <condition>Graft-versus-host-disease</condition>
    <condition>Graft Versus Host Disease</condition>
    <arm_group>
      <arm_group_label>Ruxolitinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Ruxolitinib at 5 mg twice per day (BID) beginning on Day -3 and continuing until Day 180 followed by a taper (duration of taper depends on dose of ruxolitinib at Day 180). Once a patient's counts have reached ANC &gt; 1.5 K/cumm, hemoglobin &gt; 9.0 g/dL, and platelets &gt; 50 K/cumm, ruxolitinib dosing will escalate to 10 mg BID.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ruxolitinib</intervention_name>
      <description>Ruxolitinib is provided by Incyte Corporation.</description>
      <arm_group_label>Ruxolitinib</arm_group_label>
      <other_name>Jakafi</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Patients must meet the following criteria within 30 days prior to Day -3 unless otherwise&#xD;
          noted.&#xD;
  &#xD;
            -  Diagnosis of one of the hematological malignancies listed below:&#xD;
  &#xD;
                 -  Acute myelogenous leukemia (AML) in complete morphological remission, complete&#xD;
                    remission with incomplete hematologic recovery, and complete remission with&#xD;
                    partial hematologic recovery (based on ELN Criteria47).&#xD;
  &#xD;
                 -  Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD&#xD;
                    negative by flow cytometry with sensitivity to ≤ 10-4).&#xD;
  &#xD;
                 -  Myelodysplastic syndrome with ≤ 5% blasts in bone marrow.&#xD;
  &#xD;
                 -  Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HD) in second or greater complete&#xD;
                    or partial remission.&#xD;
  &#xD;
                 -  Myelofibrosis with ≤ 10% blasts in bone marrow.&#xD;
  &#xD;
            -  Planned treatment is T cell-replete peripheral blood haploidentical donor&#xD;
               transplantation.&#xD;
  &#xD;
            -  Available HLA-haploidentical donor who meets the following criteria:&#xD;
  &#xD;
                 -  Blood-related family member, including (but not limited to) sibling, offspring,&#xD;
                    cousin, nephew, or parent. Younger donors should be prioritized.&#xD;
  &#xD;
                 -  At least 18 years of age.&#xD;
  &#xD;
                 -  HLA-haploidentical donor/recipient match by at least low-resolution typing per&#xD;
                    institutional standards.&#xD;
  &#xD;
                 -  In the investigator's opinion, is in general good health and medically able to&#xD;
                    tolerate leukapheresis required for harvesting hematopoietic stem cells.&#xD;
  &#xD;
                 -  No active hepatitis.&#xD;
  &#xD;
                 -  Negative for HTLV and HIV.&#xD;
  &#xD;
                 -  Not pregnant.&#xD;
  &#xD;
                 -  Donor selection will be in compliance with FDA guidelines as provided in 21 CFR&#xD;
                    1271 for donor eligibility&#xD;
                    https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatory&#xD;
                    Information/Guidances/Tissue/UCM091345.pdf&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.&#xD;
  &#xD;
            -  Adequate organ function as defined below:&#xD;
  &#xD;
                 -  Total bilirubin ≤ 1.5 x IULN.&#xD;
  &#xD;
                 -  AST (SGOT) and ALT (SGPT) ≤ 3.0 x IULN.&#xD;
  &#xD;
                 -  Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 45 mL/min/1.73 m2 by&#xD;
                    Cockcroft-Gault Formula.&#xD;
  &#xD;
                 -  Oxygen saturation ≥ 90% on room air.&#xD;
  &#xD;
                 -  LVEF ≥ 40%.&#xD;
  &#xD;
                 -  FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is &lt; 40%, patients&#xD;
                    will still be considered eligible if deemed safe after a pulmonary evaluation.&#xD;
  &#xD;
            -  Able to receive GVHD prophylaxis with tacrolimus, mycophenolate mofetil, and&#xD;
               cyclophosphamide.&#xD;
  &#xD;
            -  At least 18 years of age at the time of study registration&#xD;
  &#xD;
            -  The effects of ruxolitinib on the developing human fetus are unknown. For this reason,&#xD;
               women of childbearing potential and men must agree to use adequate contraception&#xD;
               (hormonal or barrier method of birth control, abstinence) prior to study entry and for&#xD;
               the duration of study participation. Should a woman become pregnant or suspect she is&#xD;
               pregnant while participating in this study, she must inform her treating physician&#xD;
               immediately. Men treated or enrolled on this protocol must also agree to use adequate&#xD;
               contraception prior to the study and for the duration of the study.&#xD;
  &#xD;
            -  Able to understand and willing to sign an IRB approved written informed consent&#xD;
               document (or that of legally authorized representative, if applicable).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior allogeneic transplant (regardless of whether donor was related, unrelated, or&#xD;
               cord). Prior autologous transplant is not exclusionary.&#xD;
  &#xD;
            -  Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of&#xD;
               ≥ 2000 as assessed by the single antigen bead assay.&#xD;
  &#xD;
            -  Known HIV or active hepatitis B or C infection. Known current and/or history of active&#xD;
               tuberculosis.&#xD;
  &#xD;
            -  Known hypersensitivity to one or more of the study agents.&#xD;
  &#xD;
            -  Planning to receive antithymocyte globulin as part of the pre-transplant conditioning&#xD;
               regimen.&#xD;
  &#xD;
            -  Currently receiving or has received any investigational drugs within the 14 days prior&#xD;
               to the first dose of study drug (Day -3).&#xD;
  &#xD;
            -  Pregnant and/or breastfeeding. Women of childbearing potential must have a negative&#xD;
               pregnancy test within 14 days of study entry.&#xD;
  &#xD;
            -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
               infection, autoimmune disease, symptomatic congestive heart failure, unstable angina&#xD;
               pectoris, or unstable cardiac arrhythmias.&#xD;
  &#xD;
            -  Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency&#xD;
               will not be excluded.&#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>Ramzi Abboud, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Washington University School of Medicine</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ramzi Abboud, M.D.</last_name>
      <phone>314-454-8304</phone>
      <email>rabboud@wustl.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Washington University School of Medicine</name>
        <address>
          <city>Saint Louis</city>
          <state>Missouri</state>
          <zip>63110</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Ramzi Abboud, M.D.</last_name>
        <phone>314-454-8304</phone>
        <email>rabboud@wustl.edu</email>
      </contact>
      <investigator>
        <last_name>Ramzi Abboud, M.D.</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Camille Abboud, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Kelly Bolton, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Amanda Cashen, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Matt Christopher, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Zachary Crees, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>John Dipersio, M.D., Ph.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Todd Fehniger, M.D., Ph.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Armin Ghobadi, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Meagan Jacoby, M.D., Ph.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Brad Kahl, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Iskra Pusic, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Mark Schroeder, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Keith Stockerl-Goldstein, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Geoffrey Uy, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Ravi Vij, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Matthew Walter, M.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Feng Gao, Ph.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://www.siteman.wustl.edu</url>
      <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 18, 2023</last_update_submitted>
    <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Haploidentical</keyword>
    <keyword>GVHD</keyword>
    <keyword>CRS</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Graft vs Host Disease</mesh_term>
      <mesh_term>Cytokine Release Syndrome</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06008808
  org study id: 23-x287
  nct id: NCT06008808
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  Allogeneic hematopoietic cell transplantation (HCT) is one of the only curative intent
        therapies available for hematologic malignancies. HLA-matched sibling donors have
        historically offered the best clinical results but are unavailable for the majority of
        patients, while most patients do have readily available haploidentical donors. One of the
        risks of a haploidentical HCT is graft vs. host disease (GVHD), but it is difficult to reduce
        the incidence of GVHD without compromising the graft vs. leukemia (GVL) effect.
  
        The hypothesis of this study is that JAK inhibition with haploidentical HCT may mitigate GVHD
        and cytokine release syndrome while retaining the GVL effect and improving engraftment.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Cumulative incidence of graft failure
  time frame: Day 35
  measure: Cumulative incidence of grades III-IV acute GVHD by MAGIC criteria
  time frame: Day 100
  measure: Cumulative incidence of grades II-IV acute GVHD by MAGIC criteria
  time frame: Day 100
  measure: Number of patients who experience cytokine release syndrome (CRS)
  time frame: Through Day 8
  measure: Treatment-related mortality
  time frame: Day 180
  description: Defined as death resulting from a transplant procedure-related complication rather than from relapse of the underlying disease or an unrelated cause
  arm group label: Ruxolitinib
  arm group type: Experimental
  description: Ruxolitinib at 5 mg twice per day (BID) beginning on Day -3 and continuing until Day 180 followed by a taper (duration of taper depends on dose of ruxolitinib at Day 180). Once a patient's counts have reached ANC > 1.5 K/cumm, hemoglobin > 9.0 g/dL, and platelets > 50 K/cumm, ruxolitinib dosing will escalate to 10 mg BID.
  intervention type: Drug
  intervention name: Ruxolitinib
  description: Ruxolitinib is provided by Incyte Corporation.
  arm group label: Ruxolitinib
  other name: Jakafi
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Ramzi Abboud, M.D.
  role: Principal Investigator
  affiliation: Washington University School of Medicine
  last name: Ramzi Abboud, M.D.
  phone: 314-454-8304
  email: rabboud@wustl.edu
  facility: 
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
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  investigator: 
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  investigator: 
  country: United States
  url: http://www.siteman.wustl.edu
  description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
  responsible party type: Sponsor
  mesh term: Graft vs Host Disease
  mesh term: Cytokine Release Syndrome
  sharing ipd: No