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/NCT05996627</url>
    </required_header>
    <id_info>
      <org_study_id>RG1123523</org_study_id>
      <secondary_id>NCI-2023-05293</secondary_id>
      <secondary_id>RG1123523</secondary_id>
      <nct_id>NCT05996627</nct_id>
    </id_info>
    <brief_title>Belumosudil for the Pre-emptive Treatment of Patients With Chronic Graft Versus Host Disease</brief_title>
    <official_title>Randomized Phase II Study of Belumosudil vs. Placebo for Preemptive Treatment of Chronic Graft Versus Host Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fred Hutchinson Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Sanofi</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Fred Hutchinson Cancer Center</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase II trial compares the effect of belumosudil to a placebo in treating patients with&#xD;
        chronic graft versus host disease. Chronic graft versus host disease remains a major&#xD;
        complication of stem cell transplantation and can involve multiple organ systems. Belumosudil&#xD;
        is a ROCK2 selective inhibitor that works to reduce the immune system response causing the&#xD;
        chronic graft versus host disease. Giving belumosudil may better treat patients with chronic&#xD;
        graft versus host disease and prevent the need for starting additional immune suppressive&#xD;
        medications.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
  &#xD;
        ARM I: Patients receive belumosudil orally (PO) daily (QD) or twice daily (BID) if taken with&#xD;
        strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles&#xD;
        repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to&#xD;
        discontinuation, in the absence of disease progression or unacceptable toxicity.&#xD;
  &#xD;
        ARM II: Patients receive a placebo PO QD or BID if taken with strong CYP3A inducers or proton&#xD;
        pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total&#xD;
        of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of&#xD;
        disease progression or unacceptable toxicity.&#xD;
  &#xD;
        Patients undergo blood sample collection on study.&#xD;
  &#xD;
        Patients follow up after completion of study medication at 30 days, and at 60 days if 12&#xD;
        cycles are completed.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">May 31, 2027</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>The study will be conducted in a double-blinded fashion</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Time to start of subsequent systemic immune suppressive treatment for chronic graft versus host disease (cGVHD)</measure>
      <time_frame>From first dose of study medication to starting a new systemic immunosuppressive agent for cGVHD therapy, up to 12 months</time_frame>
      <description>Systemic therapies include any systemic agent given for a cGVHD indication, including extracorporeal photopheresis. Will use Gray's test. Point estimates of new systemic immunosuppressive use will be obtained using cumulative incidence estimates.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Event-free survival</measure>
      <time_frame>From randomization to death, malignancy relapse or addition of a new systemic immune suppressive therapy, up to 12 months or end of study</time_frame>
      <description>Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>Up to 12 months or end of study</time_frame>
      <description>Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of relapse</measure>
      <time_frame>Up to 12 months or end of study</time_frame>
      <description>Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">82</enrollment>
    <condition>Chronic Graft Versus Host Disease</condition>
    <arm_group>
      <arm_group_label>Arm I (Belumosudil)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive belumosudil PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm II (Placebo)</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Patients receive a placebo PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Belumosudil</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Arm I (Belumosudil)</arm_group_label>
      <other_name>KD 025</other_name>
      <other_name>KD-025</other_name>
      <other_name>KD025</other_name>
      <other_name>Rho-associated Coiled-coil Kinase 2 Inhibitor KD025</other_name>
      <other_name>ROCK-II Inhibitor KD025</other_name>
      <other_name>ROCK2 Inhibitor KD025</other_name>
      <other_name>SLx 2119</other_name>
      <other_name>SLx-2119</other_name>
      <other_name>SLx2119</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Arm I (Belumosudil)</arm_group_label>
      <arm_group_label>Arm II (Placebo)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Electronic Health Record Review</intervention_name>
      <description>Ancillary study</description>
      <arm_group_label>Arm I (Belumosudil)</arm_group_label>
      <arm_group_label>Arm II (Placebo)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo Administration</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Arm II (Placebo)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  At least one diagnostic or distinctive cGVHD manifestation(s), but patients do not&#xD;
               need to meet National Institute of Health (NIH) criteria for cGVHD&#xD;
  &#xD;
            -  If eye involvement only, cGVHD must be confirmed on exam by an ophthalmologist or&#xD;
               optometrist&#xD;
  &#xD;
            -  No new immune suppressive therapy added within preceding 2 weeks prior to study&#xD;
               enrollment for any indication&#xD;
  &#xD;
                 -  Continuation of agents previously given as either GVHD prophylaxis or acute/late&#xD;
                    acute GVHD therapy are permitted. Modification of dose of these agents for&#xD;
                    targeting of therapeutic drug levels is permitted, as are decreases in existing&#xD;
                    prednisone dose based on routine clinical tapering practices. Increases in&#xD;
                    prednisone are not allowed in the 2 weeks prior to enrollment&#xD;
  &#xD;
            -  Age 18 and older&#xD;
  &#xD;
            -  Karnofsky performance score &gt;= 70&#xD;
  &#xD;
            -  Able to take oral medications&#xD;
  &#xD;
            -  Signed informed consent&#xD;
  &#xD;
            -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 3 x upper limit&#xD;
               of normal (ULN)&#xD;
  &#xD;
            -  Total bilirubin =&lt; 1.5 x ULN&#xD;
  &#xD;
            -  Glomerular filtration rate (GFR) &gt;= 30 mL/min/1.73 m^2&#xD;
  &#xD;
            -  Female subjects of childbearing potential have a negative serum or urine pregnancy&#xD;
               test at screening. Females of childbearing potential are defined as sexually mature&#xD;
               females without prior hysterectomy or who have had any evidence of menses in the past&#xD;
               12 months. However, females who have been amenorrheic for 12 or more months are still&#xD;
               considered to be of childbearing potential if the amenorrhea is possibly due to prior&#xD;
               chemotherapy, anti-estrogens, or ovarian suppression&#xD;
  &#xD;
            -  Sexually active females of childbearing potential enrolled in the study must agree to&#xD;
               use two forms of accepted methods of contraception during the course of the study and&#xD;
               for 3 months after their last dose of study drug. Effective birth control includes:&#xD;
  &#xD;
                 -  Intrauterine device (IUD) plus one barrier method&#xD;
  &#xD;
                 -  Stable doses of hormonal contraception for at least 3 months (eg, oral,&#xD;
                    injectable, implant, transdermal) plus one barrier method&#xD;
  &#xD;
                 -  2 barrier methods. Effective barrier methods are male or female condoms,&#xD;
                    diaphragms, and spermicides (creams or gel that contain a chemical to kill&#xD;
                    sperm); or&#xD;
  &#xD;
                 -  A vasectomized partner&#xD;
  &#xD;
            -  For male subjects who are sexually active and who are partners of females of&#xD;
               childbearing potential: Agreement to use two forms of contraception as per above and&#xD;
               to not donate sperm during the treatment period and for at least 3 months after the&#xD;
               last dose of study drug&#xD;
  &#xD;
            -  No evidence of active malignancy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Any systemic immune suppressive treatment for cGVHD (topical or local therapies are&#xD;
               allowed)&#xD;
  &#xD;
            -  Plan to start systemic immune suppressive therapy for cGVHD or increase steroid dose&#xD;
               within 14 days after planned start of study medication&#xD;
  &#xD;
            -  0.25 mg/kg/day or higher prednisone dose at time of screening&#xD;
  &#xD;
            -  History of non-compliance that in the investigator's opinion would interfere with&#xD;
               study participation&#xD;
  &#xD;
            -  Uncontrolled psychiatric illness&#xD;
  &#xD;
            -  Female subject who is pregnant or breast feeding&#xD;
  &#xD;
            -  Previous therapy with belumosudil&#xD;
  &#xD;
            -  Known allergy/sensitivity to belumosudil or any other ROCK2 inhibitor&#xD;
  &#xD;
            -  Treatment with another investigational agent within 28 days (or 5 half-lives,&#xD;
               whichever is greater) of enrollment&#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>Stephanie Lee, MD, MPH</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Chloe Te</last_name>
      <phone>206-667-4196</phone>
      <email>cte@fredhutch.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>Moffitt Cancer Center</name>
        <address>
          <city>Tampa</city>
          <state>Florida</state>
          <zip>33612</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Joseph Pidala, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Mass General Cancer Center</name>
        <address>
          <city>Boston</city>
          <state>Massachusetts</state>
          <zip>02114</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Zachariah DeFilipp, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Dana Farber Cancer Institute</name>
        <address>
          <city>Boston</city>
          <state>Massachusetts</state>
          <zip>02215</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Corey Cutler, MD, MPH</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Cancer Center</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Doris Ponce, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Fred Hutch/University of Washington Cancer Consortium</name>
        <address>
          <city>Seattle</city>
          <state>Washington</state>
          <zip>98109</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Chloe Te</last_name>
        <phone>206-667-4196</phone>
        <email>cte@fredhutch.org</email>
      </contact>
      <investigator>
        <last_name>Stephanie Lee, MD, MPH</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>August 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Bronchiolitis Obliterans Syndrome</mesh_term>
      <mesh_term>Graft vs Host Disease</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Belumosudil</mesh_term>
    </intervention_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/NCT05996627
  org study id: RG1123523
  secondary id: NCI-2023-05293
  secondary id: RG1123523
  nct id: NCT05996627
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase II trial compares the effect of belumosudil to a placebo in treating patients with
        chronic graft versus host disease. Chronic graft versus host disease remains a major
        complication of stem cell transplantation and can involve multiple organ systems. Belumosudil
        is a ROCK2 selective inhibitor that works to reduce the immune system response causing the
        chronic graft versus host disease. Giving belumosudil may better treat patients with chronic
        graft versus host disease and prevent the need for starting additional immune suppressive
        medications.
  OUTLINE: Patients are randomized to 1 of 2 arms.
  
        ARM I: Patients receive belumosudil orally (PO) daily (QD) or twice daily (BID) if taken with
        strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles
        repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to
        discontinuation, in the absence of disease progression or unacceptable toxicity.
  
        ARM II: Patients receive a placebo PO QD or BID if taken with strong CYP3A inducers or proton
        pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total
        of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of
        disease progression or unacceptable toxicity.
  
        Patients undergo blood sample collection on study.
  
        Patients follow up after completion of study medication at 30 days, and at 60 days if 12
        cycles are completed.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: The study will be conducted in a double-blinded fashion
  measure: Time to start of subsequent systemic immune suppressive treatment for chronic graft versus host disease (cGVHD)
  time frame: From first dose of study medication to starting a new systemic immunosuppressive agent for cGVHD therapy, up to 12 months
  description: Systemic therapies include any systemic agent given for a cGVHD indication, including extracorporeal photopheresis. Will use Gray's test. Point estimates of new systemic immunosuppressive use will be obtained using cumulative incidence estimates.
  measure: Event-free survival
  time frame: From randomization to death, malignancy relapse or addition of a new systemic immune suppressive therapy, up to 12 months or end of study
  description: Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.
  measure: Overall survival
  time frame: Up to 12 months or end of study
  description: Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.
  measure: Rate of relapse
  time frame: Up to 12 months or end of study
  description: Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.
  arm group label: Arm I (Belumosudil)
  arm group type: Experimental
  description: Patients receive belumosudil PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.
  arm group label: Arm II (Placebo)
  arm group type: Placebo Comparator
  description: Patients receive a placebo PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.
  intervention type: Drug
  intervention name: Belumosudil
  description: Given PO
  arm group label: Arm I (Belumosudil)
  other name: KD 025
  other name: KD-025
  other name: KD025
  other name: Rho-associated Coiled-coil Kinase 2 Inhibitor KD025
  other name: ROCK-II Inhibitor KD025
  other name: ROCK2 Inhibitor KD025
  other name: SLx 2119
  other name: SLx-2119
  other name: SLx2119
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Arm I (Belumosudil)
  arm group label: Arm II (Placebo)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Other
  intervention name: Electronic Health Record Review
  description: Ancillary study
  arm group label: Arm I (Belumosudil)
  arm group label: Arm II (Placebo)
  intervention type: Drug
  intervention name: Placebo Administration
  description: Given PO
  arm group label: Arm II (Placebo)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Stephanie Lee, MD, MPH
  role: Principal Investigator
  affiliation: Fred Hutch/University of Washington Cancer Consortium
  last name: Chloe Te
  phone: 206-667-4196
  email: cte@fredhutch.org
  facility: 
  investigator: 
  facility: 
  investigator: 
  facility: 
  investigator: 
  facility: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Bronchiolitis Obliterans Syndrome
  mesh term: Graft vs Host Disease
  mesh term: Belumosudil
  sharing ipd: No