<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/NCT03286530</url>
  </required_header>
  <id_info>
    <org_study_id>17-273</org_study_id>
    <nct_id>NCT03286530</nct_id>
  </id_info>
  <brief_title>Ruxolitinib + Allogeneic Stem Cell Transplantation in AML</brief_title>
  <official_title>Phase II Study of Maintenance Ruxolitinib After Allogeneic Stem Cell Transplantation for Older Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) in Complete Remission</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical College of Wisconsin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</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 research study is studying a drug that may help decrease the chances of relapse after&#xD;
      Allogeneic Stem Cell transplantation for Acute Myeloid Leukemia. The name of the study drug&#xD;
      involved in this study is:&#xD;
&#xD;
      • Ruxolitinib&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Phase II clinical trial. Phase II clinical trials test the safety&#xD;
      and effectiveness of an investigational drug to learn whether the drug works in treating a&#xD;
      specific disease. &quot;Investigational&quot; means that the drug is being studied.&#xD;
&#xD;
      The FDA (the U.S. Food and Drug Administration) has not approved ruxolitinib for this&#xD;
      specific disease but it has been approved for other blood diseases.&#xD;
&#xD;
      In this research study, investigators are trying to discover if ruxolitinib will decrease&#xD;
      chances of relapse after having an allogeneic stem cell transplantation.&#xD;
&#xD;
      Ruxolitinib is a medication that blocks certain proteins called tyrosine kinases.&#xD;
      Specifically, it blocks tyrosine kinases called JAK2. Many cancers have over active &quot;cell&#xD;
      signaling.&quot; What this means is that certain functions in the cancer cells never turn off and&#xD;
      this makes them grow in an uncontrolled way. Ruxolitinib, shuts down the pathway that depends&#xD;
      on the JAK2 tyrosine kinases. The JAK2 pathway is over active with acute myeloid leukemia.&#xD;
      Ruxolitinib has also been shown to lower the rates of graft versus host disease, a&#xD;
      complication of transplant. The exact way ruxolitinib does this is not yet clear but it may&#xD;
      have to do with its ability to block the JAK2 pathway since this pathway can also lead to&#xD;
      inflammation in the body.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 3, 2017</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2024</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>1-year GVHD/relapse free survival rate (GRFS rate)</measure>
    <time_frame>1 Year</time_frame>
    <description>The number of participants surviving after one year that have not experienced graft-versus-host disease (GVHD) or graft relapse (GRFS rate).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Until disease progression or death from any cause, approximately 5 years</time_frame>
    <description>Kaplan-Meier estimates of progression free survival (PFS) will be calculated, with patients without an event being censored at last date of contact</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Until death, approximately 5 years</time_frame>
    <description>Overall survival is measured as the time from the hematopoietic stem cell transplantation (HSCT) until death. Participants without an event will be censored at the date of last contact.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of drug related toxicities</measure>
    <time_frame>2 Years</time_frame>
    <description>Cumulative incidence of treatment related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE 4). Early deaths from all other causes are considered a competing risk.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Relapse</measure>
    <time_frame>2 Years</time_frame>
    <description>The amount of time from the hematopoietic stem cell transplantation (HSCT) until disease relapse. Relapse is the recurrence of cancer after having a bone marrow biopsy without evidence of cancer. Time to treatment-related mortality is considered a competing risk.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment-related mortality (TRM)</measure>
    <time_frame>2 Years</time_frame>
    <description>The amount of time between receiving the HSCT and death due to a treatment related cause. Time to relapse is considered a competing risk.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">64</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Acute Myeloid Leukemia in Remission</condition>
  <condition>Allogeneic Stem Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>Ruxolitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following a standard of care allogeneic stem cell transplantation, participants will be started on Ruxolitinib. Ruxolitinib is administered orally 2 times per day at a fixed dose. Each study treatment cycle lasts 28 days. Up to 24 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Patients who fulfill eligibility criteria will be entered into the trial to receive Ruxolitinib.&#xD;
After the screening procedures confirm participation in the research study. The participant will be given a drug diary. The participant will be asked to document information in the drug diary about the study treatment.</description>
    <arm_group_label>Ruxolitinib</arm_group_label>
    <other_name>Jakafi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must have pathologically confirmed AML in CR1 as defined by:&#xD;
&#xD;
               -  Bone marrow biopsy with &lt; 5% blasts&#xD;
&#xD;
               -  No clusters or collections of blast cells&#xD;
&#xD;
               -  No extramedullary leukemia&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1000/µL (achieved post-induction at some point)&#xD;
&#xD;
               -  Please note that full platelet recovery is not necessary, and thus, patients&#xD;
                  achieving CRp are eligible.&#xD;
&#xD;
                  ---Or participants have pathologically confirmed MDS as defined by:&#xD;
&#xD;
               -  Bone marrow biopsy with &lt;10% blasts&#xD;
&#xD;
               -  Patients receiving MDS-directed therapy must be off treatment for &gt; 2 weeks prior&#xD;
                  to start of conditioning.&#xD;
&#xD;
          -  Participants must be designated to undergo reduced intensity allogeneic peripheral&#xD;
             blood hematopoietic stem cell transplantation (HCT). Consent will be obtained prior to&#xD;
             admission for HCT. The following HCT conditions must be planned:&#xD;
&#xD;
               -  Donors must be 8/8 HLA-matched (at the allele level) as defined by matching at&#xD;
                  HLA-A, -B, -DR and -C who pass institutional standard to serve as a peripheral&#xD;
                  blood stem cell donor&#xD;
&#xD;
               -  Donor grafts must be G-CSF mobilized peripheral blood stem cells with dose and&#xD;
                  apheresis logistics at the discretion of institutional standard&#xD;
&#xD;
               -  Conditioning therapy will be one of the following 3 options:&#xD;
&#xD;
                    -  Fludarabine / Melphalan where fludarabine is ≥ 90 mg/m2 IV total dose and&#xD;
                       melphalan is 100-140 mg/m2 IV total dose. Exact logistics of administration&#xD;
                       are at the discretion of institutional standard.&#xD;
&#xD;
                    -  Fludarabine / Busulfan where fludarabine is ≥ 90 mg/m2 IV total dose and&#xD;
                       busulfan = 6.4 mg/kg IV total dose. Exact logistics of administration are at&#xD;
                       the discretion of institutional standard.&#xD;
&#xD;
                    -  Fludarabine / Busulfan where fludarabine is ≥ 90 mg/m2 IV total dose and&#xD;
                       busulfan is dosed to achieve AUC of 4000 µmol/min based on a&#xD;
                       pharmacokinetics determined from a test dose. Exact logistics are at the&#xD;
                       discretion of institutional standard.&#xD;
&#xD;
                    -  GVHD prophylaxis is comprised of tacrolimus / short course methotrexate as&#xD;
                       defined by tacrolimus started prior to day 0 of HCT and methotrexate given&#xD;
                       after HCT on days +1, +3 and +6 ± +11 at a dose of 5-10 mg/m2 IV. Exact&#xD;
                       logistics are at the discretion of the treating institution.&#xD;
&#xD;
          -  Age ≥ 60 and ≤ 80 years old&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Male participants must agree to use an acceptable method for contraception during the&#xD;
             entire study treatment period and through 6 months after the last dose of treatment.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have had a prior allogeneic HSCT.&#xD;
&#xD;
          -  Patients without normal organ function defined as follows:&#xD;
&#xD;
               -  AST (SGOT), ALT (SGPT) and Alkaline Phosphatase &gt;3 × institutional Upper Limit of&#xD;
                  Normal (ULN)&#xD;
&#xD;
               -  Direct bilirubin &gt;2.0 mg/dL&#xD;
&#xD;
               -  Adequate renal function as defined by calculated creatinine clearance ≤ 40 mL/min&#xD;
                  (Cockcroft-Gault formula)&#xD;
&#xD;
          -  Have a history of other malignancy(ies) unless:&#xD;
&#xD;
               -  They have been disease-free for at least 5 years and are deemed by the treating&#xD;
                  investigator to be at low risk for recurrence of that malignancy,&#xD;
&#xD;
                  --- or&#xD;
&#xD;
               -  The only cancer they have had is cervical cancer in situ, or basal cell or&#xD;
                  squamous cell carcinoma of the skin&#xD;
&#xD;
          -  Have a chronic or active infection that requires systemic antibiotics, antifungal or&#xD;
             antiviral treatment.&#xD;
&#xD;
          -  Have current or a history of congestive heart failure New York Heart Association&#xD;
             (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction&#xD;
             (LVEF &lt; 40%, as measured by MUGA scan or echocardiogram)&#xD;
&#xD;
          -  Have an uncontrolled intercurrent illness including, but not limited to, ongoing&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Have active uncontrolled infection. An active uncontrolled infection is defined as&#xD;
             hemodynamic instability attributable to sepsis or new symptoms, worsening physical&#xD;
             signs, or radiographic findings attributable to infection. Persisting fever without&#xD;
             signs or symptoms will not be interpreted as an active uncontrolled infection.&#xD;
&#xD;
          -  Be HIV-positive&#xD;
&#xD;
          -  Have a systemic infection requiring IV antibiotic therapy, nor any other severe&#xD;
             infection&#xD;
&#xD;
          -  Planned use of ex vivo or in vivo T-cell depletion&#xD;
&#xD;
          -  Have current or a history of ventricular or life-threatening arrhythmias or diagnosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gabriell Hobbs, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gabriella Hobbs, MD</last_name>
    <phone>617-726-8747</phone>
    <email>Ghobbs@mgh.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ajoy Dias, MD</last_name>
      <phone>617-667-9920</phone>
    </contact>
    <investigator>
      <last_name>Ajoy Dias, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gabriella Hobbs, MD</last_name>
      <phone>617-726-8748</phone>
    </contact>
    <investigator>
      <last_name>Gabriella Hobbs, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mark Schroeder, MD</last_name>
      <email>markschroeder@wustl.edu</email>
    </contact>
    <investigator>
      <last_name>Mark Schroeder, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sumithira Vasu, MBBS</last_name>
      <email>Sumithira.Vasu@osumc.edu</email>
    </contact>
    <investigator>
      <last_name>Sumithira Vasu, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37235</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bhagirathbhai Dholaria, MD</last_name>
      <email>Bhagirathbhai.r.dholaria@vumc.org</email>
    </contact>
    <investigator>
      <last_name>Bhagirathbhai Dholaria, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Wauwatosa</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sameem Abedin, MD</last_name>
      <email>sabedin@mcw.edu</email>
    </contact>
    <investigator>
      <last_name>Sameem Abedin, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>March 24, 2023</last_update_submitted>
  <last_update_submitted_qc>March 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Gabriela Hobbs</investigator_full_name>
    <investigator_title>Prinicipal Investigator</investigator_title>
  </responsible_party>
  <keyword>Acute Myeloid Leukemia</keyword>
  <keyword>Acute Myeloid Leukemia in Remission</keyword>
  <keyword>Allogenic Stem Cell Transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03286530
org study id: 17-273
nct id: NCT03286530
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study is studying a drug that may help decrease the chances of relapse after
      Allogeneic Stem Cell transplantation for Acute Myeloid Leukemia. The name of the study drug
      involved in this study is:

      • Ruxolitinib
This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved ruxolitinib for this
      specific disease but it has been approved for other blood diseases.

      In this research study, investigators are trying to discover if ruxolitinib will decrease
      chances of relapse after having an allogeneic stem cell transplantation.

      Ruxolitinib is a medication that blocks certain proteins called tyrosine kinases.
      Specifically, it blocks tyrosine kinases called JAK2. Many cancers have over active "cell
      signaling." What this means is that certain functions in the cancer cells never turn off and
      this makes them grow in an uncontrolled way. Ruxolitinib, shuts down the pathway that depends
      on the JAK2 tyrosine kinases. The JAK2 pathway is over active with acute myeloid leukemia.
      Ruxolitinib has also been shown to lower the rates of graft versus host disease, a
      complication of transplant. The exact way ruxolitinib does this is not yet clear but it may
      have to do with its ability to block the JAK2 pathway since this pathway can also lead to
      inflammation in the body.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 1-year GVHD/relapse free survival rate (GRFS rate)
time frame: 1 Year
description: The number of participants surviving after one year that have not experienced graft-versus-host disease (GVHD) or graft relapse (GRFS rate).
measure: Progression Free Survival
time frame: Until disease progression or death from any cause, approximately 5 years
description: Kaplan-Meier estimates of progression free survival (PFS) will be calculated, with patients without an event being censored at last date of contact
measure: Overall Survival
time frame: Until death, approximately 5 years
description: Overall survival is measured as the time from the hematopoietic stem cell transplantation (HSCT) until death. Participants without an event will be censored at the date of last contact.
measure: Cumulative incidence of drug related toxicities
time frame: 2 Years
description: Cumulative incidence of treatment related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE 4). Early deaths from all other causes are considered a competing risk.
measure: Time to Relapse
time frame: 2 Years
description: The amount of time from the hematopoietic stem cell transplantation (HSCT) until disease relapse. Relapse is the recurrence of cancer after having a bone marrow biopsy without evidence of cancer. Time to treatment-related mortality is considered a competing risk.
measure: Time to treatment-related mortality (TRM)
time frame: 2 Years
description: The amount of time between receiving the HSCT and death due to a treatment related cause. Time to relapse is considered a competing risk.
arm group label: Ruxolitinib
arm group type: Experimental
description: Following a standard of care allogeneic stem cell transplantation, participants will be started on Ruxolitinib. Ruxolitinib is administered orally 2 times per day at a fixed dose. Each study treatment cycle lasts 28 days. Up to 24 cycles.
intervention type: Drug
intervention name: Ruxolitinib
description: Patients who fulfill eligibility criteria will be entered into the trial to receive Ruxolitinib.
After the screening procedures confirm participation in the research study. The participant will be given a drug diary. The participant will be asked to document information in the drug diary about the study treatment.
arm group label: Ruxolitinib
other name: Jakafi
criteria: 
gender: All
minimum age: 60 Years
maximum age: 80 Years
healthy volunteers: No
last name: Gabriell Hobbs, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Gabriella Hobbs, MD
phone: 617-726-8747
email: Ghobbs@mgh.harvard.edu
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Gabriela Hobbs
investigator title: Prinicipal Investigator
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
sharing ipd: No