<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/NCT02251821</url>
  </required_header>
  <id_info>
    <org_study_id>9033</org_study_id>
    <secondary_id>NCI-2014-01882</secondary_id>
    <secondary_id>9033</secondary_id>
    <secondary_id>RG9214017</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <nct_id>NCT02251821</nct_id>
  </id_info>
  <brief_title>JAK Inhibitor Before Donor Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis</brief_title>
  <official_title>JAK Inhibitor Prior to Allogeneic Stem Cell Transplant for Patients With Primary and Secondary Myelofibrosis: A Prospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fred Hutchinson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Incyte Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</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 studies how well giving a JAK inhibitor before a donor stem cell&#xD;
      transplant works in treating patients with myelofibrosis that developed without another&#xD;
      condition (primary) or evolved from other bone marrow disorders (secondary). JAK inhibitors&#xD;
      are a class of drugs that may stop the growth of abnormal cells by blocking an enzyme needed&#xD;
      for cell growth. Giving a JAK inhibitor such as ruxolitinib before a donor stem cell&#xD;
      transplant may help reduce symptoms of myelofibrosis such as inflammation and enlargement of&#xD;
      the spleen, improve the patient's general physical condition, and prevent complications from&#xD;
      occurring after the transplant. Infusing healthy stem cells from a donor into the patient may&#xD;
      help the patient's bone marrow work normally and make stem cells, red blood cells, white&#xD;
      blood cells, and platelets. Giving a JAK inhibitor before a donor stem cell transplant may&#xD;
      help improve transplant outcomes in patients with myelofibrosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE:&#xD;
&#xD;
      PART 1: Patients receive ruxolitinib orally (PO) twice daily (BID) from at least 8 weeks&#xD;
      prior to the start of conditioning through day -4 before transplantation, with a taper&#xD;
      schedule reducing the dose every 2-3 days beginning after day -4.&#xD;
&#xD;
      PART 2: Patients are assigned to 1 of 2 conditioning regimens at the discretion of the&#xD;
      clinical provider and Clinical Coordinators Office (CCO).&#xD;
&#xD;
      MYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1&#xD;
      hour on days -8 to -6 (umbilical cord blood transplant recipients only), cyclophosphamide IV&#xD;
      on days -7 and -6, and busulfan IV over 3 hours on days -5 to -2.&#xD;
&#xD;
      REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 1 hour on days&#xD;
      -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. Patients also undergo&#xD;
      total-body irradiation (TBI) on day -1 (umbilical cord blood transplant recipients only).&#xD;
&#xD;
      TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant or umbilical cord&#xD;
      blood transplant on day 0.&#xD;
&#xD;
      GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously&#xD;
      (inpatients) or over 1-2 hours twice daily (BID) (outpatients) or orally (PO) BID on days -1&#xD;
      to +180 (patients receiving related or unrelated stem cells) or days -3 to +180 (patients&#xD;
      receiving umbilical cord blood) with taper beginning on day +56 (related donor recipients) or&#xD;
      +100 (unrelated donor or umbilical cord blood recipients) in the absence of GVHD. Patients&#xD;
      also receive methotrexate IV on days +1, +3, +6, and +11 (related and unrelated donor&#xD;
      recipients only) or mycophenolate mofetil IV or PO every 8 hours on days 0 to +40 with taper&#xD;
      to day +96 (umbilical cord blood transplant recipients only).&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 6 months, 1 year, and then&#xD;
      yearly for 4 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 20, 2014</start_date>
  <completion_date type="Anticipated">December 28, 2025</completion_date>
  <primary_completion_date type="Actual">December 28, 2022</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>Probability of 2-year survival in patients with myelofibrosis (MF) who receive treatment with a JAK inhibitor followed by an allogeneic transplant</measure>
    <time_frame>At 2 years</time_frame>
    <description>The exact benchmark that will be used for comparison will be determined from the mix of Dynamic International Prognostic Scoring System (DIPSS) categories among those enrolled and treated with JAK on the current trial. From this mix, an expected two-year survival will be created as a weighted average of the data cited above. This weighted average will be used as the benchmark to which the data from the current trial will be compared.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of acute graft versus host disease (GVHD)</measure>
    <time_frame>Up to 70 days post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of chronic GVHD</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of relapse</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-relapse mortality (NRM)</measure>
    <time_frame>Day 100</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-relapse mortality (NRM)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall incidence of primary graft failure/rejection</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall incidence of secondary graft failure/rejection</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">99</enrollment>
  <condition>Primary Myelofibrosis</condition>
  <condition>Secondary Myelofibrosis</condition>
  <arm_group>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive a ruxolitinib and undergo myeloablative or reduced-intensity conditioning followed by transplant and GVHD prophylaxis; see detailed description.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Undergo allogeneic hematopoietic stem cell transplant</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>Allogeneic Hematopoietic Cell Transplantation</other_name>
    <other_name>allogeneic stem cell transplantation</other_name>
    <other_name>HSC</other_name>
    <other_name>HSCT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Busulfan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>1, 4-Bis[methanesulfonoxy]butane</other_name>
    <other_name>BUS</other_name>
    <other_name>Bussulfam</other_name>
    <other_name>Busulfanum</other_name>
    <other_name>Busulfex</other_name>
    <other_name>Busulphan</other_name>
    <other_name>CB 2041</other_name>
    <other_name>CB-2041</other_name>
    <other_name>Glyzophrol</other_name>
    <other_name>GT 41</other_name>
    <other_name>GT-41</other_name>
    <other_name>Joacamine</other_name>
    <other_name>Methanesulfonic Acid Tetramethylene Ester</other_name>
    <other_name>Methanesulfonic acid, tetramethylene ester</other_name>
    <other_name>Mielucin</other_name>
    <other_name>Misulban</other_name>
    <other_name>Misulfan</other_name>
    <other_name>Mitosan</other_name>
    <other_name>Myeleukon</other_name>
    <other_name>Myeloleukon</other_name>
    <other_name>Myelosan</other_name>
    <other_name>Mylecytan</other_name>
    <other_name>Myleran</other_name>
    <other_name>Sulfabutin</other_name>
    <other_name>Tetramethylene Bis(methanesulfonate)</other_name>
    <other_name>Tetramethylene bis[methanesulfonate]</other_name>
    <other_name>WR-19508</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine Phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>2-F-ara-AMP</other_name>
    <other_name>9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-</other_name>
    <other_name>Beneflur</other_name>
    <other_name>Fludara</other_name>
    <other_name>SH T 586</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>Alanine Nitrogen Mustard</other_name>
    <other_name>CB-3025</other_name>
    <other_name>L-PAM</other_name>
    <other_name>L-Phenylalanine mustard</other_name>
    <other_name>L-Sarcolysin</other_name>
    <other_name>L-Sarcolysin Phenylalanine mustard</other_name>
    <other_name>L-Sarcolysine</other_name>
    <other_name>Melphalanum</other_name>
    <other_name>Phenylalanine Mustard</other_name>
    <other_name>Phenylalanine Nitrogen Mustard</other_name>
    <other_name>Sarcoclorin</other_name>
    <other_name>Sarkolysin</other_name>
    <other_name>WR-19813</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>Abitrexate</other_name>
    <other_name>Alpha-Methopterin</other_name>
    <other_name>Amethopterin</other_name>
    <other_name>Brimexate</other_name>
    <other_name>CL 14377</other_name>
    <other_name>CL-14377</other_name>
    <other_name>Emtexate</other_name>
    <other_name>Emthexat</other_name>
    <other_name>Emthexate</other_name>
    <other_name>Farmitrexat</other_name>
    <other_name>Fauldexato</other_name>
    <other_name>Folex</other_name>
    <other_name>Folex PFS</other_name>
    <other_name>Lantarel</other_name>
    <other_name>Ledertrexate</other_name>
    <other_name>Lumexon</other_name>
    <other_name>Maxtrex</other_name>
    <other_name>Medsatrexate</other_name>
    <other_name>Metex</other_name>
    <other_name>Methoblastin</other_name>
    <other_name>Methotrexate LPF</other_name>
    <other_name>Methotrexate Methylaminopterin</other_name>
    <other_name>Methotrexatum</other_name>
    <other_name>Metotrexato</other_name>
    <other_name>Metrotex</other_name>
    <other_name>Mexate</other_name>
    <other_name>Mexate-AQ</other_name>
    <other_name>MTX</other_name>
    <other_name>Novatrex</other_name>
    <other_name>Rheumatrex</other_name>
    <other_name>Texate</other_name>
    <other_name>Tremetex</other_name>
    <other_name>Trexeron</other_name>
    <other_name>Trixilem</other_name>
    <other_name>WR-19039</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Given IV or PO</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>Cellcept</other_name>
    <other_name>MMF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>INCB-18424</other_name>
    <other_name>INCB18424</other_name>
    <other_name>Oral JAK Inhibitor INCB18424</other_name>
    <other_name>Jakafi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Given IV or PO</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>FK 506</other_name>
    <other_name>Fujimycin</other_name>
    <other_name>Hecoria</other_name>
    <other_name>Prograf</other_name>
    <other_name>Protopic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total-Body Irradiation</intervention_name>
    <description>Undergo TBI</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>TOTAL BODY IRRADIATION</other_name>
    <other_name>Whole-Body Irradiation</other_name>
    <other_name>SCT_TBI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Umbilical Cord Blood Transplantation</intervention_name>
    <description>Undergo umbilical cord blood transplant</description>
    <arm_group_label>Treatment (ruxolitinib, transplant)</arm_group_label>
    <other_name>Cord Blood Transplantation</other_name>
    <other_name>UCB transplantation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        PART 1:&#xD;
&#xD;
          -  PART 1: Disease criteria&#xD;
&#xD;
               -  Diagnosis of primary MF (PMF) as defined by the 2008 World Health Organization&#xD;
                  classification system or diagnosis of secondary MF as defined by the&#xD;
                  International Working Group (IWG) for Myeloproliferative Neoplasms Research and&#xD;
                  Treatment criteria&#xD;
&#xD;
               -  Patients meeting the criteria for intermediate-1, intermediate-2 or high-risk&#xD;
                  disease by the Dynamic International Prognostic Scoring System (DIPSS) or&#xD;
                  DIPSS-plus scoring system&#xD;
&#xD;
          -  PART 1: Ability to understand and the willingness to sign a written informed consent&#xD;
             document&#xD;
&#xD;
          -  PART 1: Patient must be a potential hematopoietic stem cell transplant candidate&#xD;
&#xD;
        PART 2:&#xD;
&#xD;
          -  PART 2: Meeting criteria for 1st phase as above, at time of initiation of JAK&#xD;
             inhibitor, including ability to understand and willingness to sign a written informed&#xD;
             consent; patients arriving to our institution for transplant and not enrolled in Part&#xD;
             1 may still be enrolled in Part 2 if Part 1 criteria met; these patients will have&#xD;
             Part 1 endpoints transcribed from medical records&#xD;
&#xD;
          -  PART 2: Received ruxolitinib for at least 8 weeks immediately prior to conditioning&#xD;
             and be able to continue until Day -4 pre-transplant&#xD;
&#xD;
          -  PART 2: Performance status score&#xD;
&#xD;
               -  Karnofsky &gt;= 70&#xD;
&#xD;
          -  PART 2: Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hr&#xD;
             urine creatinine clearance must be &gt; 60 ml/min&#xD;
&#xD;
          -  PART 2: Total serum bilirubin must be &lt; 3 mg/dL unless the elevation is thought to be&#xD;
             due to Gilbert's disease or hemolysis&#xD;
&#xD;
          -  PART 2: Transaminases must be &lt; 3 x the upper limit of normal&#xD;
&#xD;
          -  PART 2: Patients with clinical or laboratory evidence of liver disease will be&#xD;
             evaluated for the cause of liver disease, its clinical severity in terms of liver&#xD;
             function, and the degree of portal hypertension; patients with fulminant liver&#xD;
             failure, cirrhosis with evidence of portal hypertension or bridging fibrosis,&#xD;
             alcoholic hepatitis, hepatic encephalopathy, or correctable hepatic synthetic&#xD;
             dysfunction evidenced by prolongation of the prothrombin time, ascites related to&#xD;
             portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral&#xD;
             hepatitis with total serum bilirubin &gt; 3 mg/dL, and symptomatic biliary disease will&#xD;
             be excluded&#xD;
&#xD;
          -  PART 2: Diffusing capacity of the lung for carbon monoxide (DLCO) corrected &gt; 60%&#xD;
             normal&#xD;
&#xD;
               -  May not be on supplemental oxygen&#xD;
&#xD;
          -  PART 2: Left ventricular ejection fraction &gt; 40% OR&#xD;
&#xD;
          -  PART 2: Shortening fraction &gt; 26%&#xD;
&#xD;
          -  PART 2: Comorbidity Index &lt; 5 at the time of pre-transplant evaluation&#xD;
&#xD;
        DONOR:&#xD;
&#xD;
          -  DONOR: Human leukocyte antigen (HLA)-matched or 1 antigen mismatched sibling donor&#xD;
&#xD;
          -  DONOR: 10 of 10 HLA-matched or 1 allele mismatched (9 of 10) unrelated donor&#xD;
&#xD;
          -  DONOR: Peripheral blood is preferred over bone marrow for non-umbilical cord blood&#xD;
             recipients&#xD;
&#xD;
          -  DONOR: Umbilical cord blood units will be selected according to the following&#xD;
             umbilical cord blood graft selection criteria; one or 2 cord blood (CB) units may be&#xD;
             used to achieve the required cell dose&#xD;
&#xD;
          -  DONOR: The CB graft(s) must be matched at 4-6 HLA-A, B, DR Beta 1 (DRB1) loci with the&#xD;
             recipient and therefore may include 0-2 mismatches at the A or B or DRB1 loci; unit&#xD;
             selection will be based on cryopreserved nucleated cell dose and intermediate&#xD;
             resolution A, B antigen and DRB1 allele typing for determination of HLA-match; while&#xD;
             HLA-C antigen/allele level typing is not considered in the matching criteria, if&#xD;
             available, it may be used to optimize unit selection&#xD;
&#xD;
          -  DONOR: Selection of two CB units is allowed to provide sufficient cell dose (see below&#xD;
             for algorithm to determine single versus double unit transplant); when multiple units&#xD;
             are selected, the following rules apply:&#xD;
&#xD;
               -  The CB unit with the least HLA disparity (with the patient) will be selected&#xD;
                  first (i.e., selection priority is 6/6 match &gt; 5/6 match &gt; 4/6 match); additional&#xD;
                  CB units then may be selected to achieve the required cell dose, as outlined&#xD;
                  below; if a second unit is required, this unit will be the unit that most closely&#xD;
                  HLA matches the patient and meets minimum size criteria outlined below of at&#xD;
                  least 1.5 x 10^7 total nucleated cells (TNC)/kg (i.e. a smaller, more closely&#xD;
                  matched unit will be selected over a larger, less well matched unit as long as&#xD;
                  minimum criteria are met)&#xD;
&#xD;
               -  If two CB units are used:&#xD;
&#xD;
                    -  The total cell dose of the combined units must be at least 3.0 x 10^7 TNC&#xD;
                       per kilogram recipient weight&#xD;
&#xD;
                    -  Each CB unit MUST contain at least 1.5 x 10^7 TNC per kilogram recipient&#xD;
                       weight&#xD;
&#xD;
               -  Algorithm for determining single versus double unit cord blood transplant:&#xD;
&#xD;
                    -  Match grade 6/6: TNC dose &gt;= 2.5 x 10^7/kg&#xD;
&#xD;
                    -  Match grade 5/6, 4/6: TNC dose &gt;= 4.0 (+/- 0.5) x 10^7/kg&#xD;
&#xD;
          -  DONOR: General comments:&#xD;
&#xD;
               -  Units will be selected first based on the TNC dose and HLA matching&#xD;
&#xD;
               -  Cluster of differentiation (CD)34+ cell dose will not be used for unit selection&#xD;
                  unless 2 units of equal HLA-match grade are available; in this case, the unit&#xD;
                  with the larger CD34+ cell dose (if data available) should be selected&#xD;
&#xD;
               -  A CB unit that is 5/6 mismatched but homozygous at the locus of mismatch should&#xD;
                  be chosen over a 5/6 unit with bidirectional mismatch even if the latter unit is&#xD;
                  larger (has more cells); this also applies to 4/6 units; this is only applicable&#xD;
                  to choosing units within a given match grade&#xD;
&#xD;
               -  Other factors to be considered:&#xD;
&#xD;
                    -  Within the same HLA match grade, matching at DR takes preference&#xD;
&#xD;
                    -  Cord blood banks located in the United States are preferred&#xD;
&#xD;
               -  Up to 5% of the cord blood product(s), when ready for infusion, may be withheld&#xD;
                  for research purposes as long as thresholds for infused TNC dose are met; these&#xD;
                  products will be used to conduct studies involving the kinetics of engraftment&#xD;
                  and immunobiology of double cord transplantation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        PART 1:&#xD;
&#xD;
          -  PART 1: Evidence of human immunodeficiency virus (HIV) infection or known HIV positive&#xD;
             serology&#xD;
&#xD;
          -  PART 1: Uncontrolled viral, bacterial, or fungal infections at the time of study&#xD;
             enrollment&#xD;
&#xD;
          -  PART 1: History of prior allogeneic transplant&#xD;
&#xD;
          -  PART 1: Pregnant or breastfeeding (only if patients have not been started on&#xD;
             ruxolitinib [Rux] by their primary oncologist prior to enrollment)&#xD;
&#xD;
        PART 2:&#xD;
&#xD;
          -  PART 2: Uncontrolled viral or bacterial infection at the time of study enrollment&#xD;
&#xD;
          -  PART 2: Active or recent (prior 6 month) invasive fungal infection without infectious&#xD;
             disease (ID) consult and approval&#xD;
&#xD;
          -  PART 2: History of HIV infection&#xD;
&#xD;
          -  PART 2: Pregnant or breastfeeding&#xD;
&#xD;
          -  PART 2: Patients without an HLA-identical or 1-allele-mismatched related donor or&#xD;
             unrelated donor or umbilical cord blood units that meet transplant criteria&#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>Rachel B. Salit</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>January 10, 2023</last_update_submitted>
  <last_update_submitted_qc>January 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 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>Neoplasm Metastasis</mesh_term>
    <mesh_term>Primary Myelofibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Melphalan</mesh_term>
    <mesh_term>Busulfan</mesh_term>
    <mesh_term>Mechlorethamine</mesh_term>
    <mesh_term>Nitrogen Mustard Compounds</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02251821
org study id: 9033
secondary id: NCI-2014-01882
secondary id: 9033
secondary id: RG9214017
secondary id: P30CA015704
nct id: NCT02251821
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well giving a JAK inhibitor before a donor stem cell
      transplant works in treating patients with myelofibrosis that developed without another
      condition (primary) or evolved from other bone marrow disorders (secondary). JAK inhibitors
      are a class of drugs that may stop the growth of abnormal cells by blocking an enzyme needed
      for cell growth. Giving a JAK inhibitor such as ruxolitinib before a donor stem cell
      transplant may help reduce symptoms of myelofibrosis such as inflammation and enlargement of
      the spleen, improve the patient's general physical condition, and prevent complications from
      occurring after the transplant. Infusing healthy stem cells from a donor into the patient may
      help the patient's bone marrow work normally and make stem cells, red blood cells, white
      blood cells, and platelets. Giving a JAK inhibitor before a donor stem cell transplant may
      help improve transplant outcomes in patients with myelofibrosis.
OUTLINE:

      PART 1: Patients receive ruxolitinib orally (PO) twice daily (BID) from at least 8 weeks
      prior to the start of conditioning through day -4 before transplantation, with a taper
      schedule reducing the dose every 2-3 days beginning after day -4.

      PART 2: Patients are assigned to 1 of 2 conditioning regimens at the discretion of the
      clinical provider and Clinical Coordinators Office (CCO).

      MYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1
      hour on days -8 to -6 (umbilical cord blood transplant recipients only), cyclophosphamide IV
      on days -7 and -6, and busulfan IV over 3 hours on days -5 to -2.

      REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 1 hour on days
      -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. Patients also undergo
      total-body irradiation (TBI) on day -1 (umbilical cord blood transplant recipients only).

      TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant or umbilical cord
      blood transplant on day 0.

      GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously
      (inpatients) or over 1-2 hours twice daily (BID) (outpatients) or orally (PO) BID on days -1
      to +180 (patients receiving related or unrelated stem cells) or days -3 to +180 (patients
      receiving umbilical cord blood) with taper beginning on day +56 (related donor recipients) or
      +100 (unrelated donor or umbilical cord blood recipients) in the absence of GVHD. Patients
      also receive methotrexate IV on days +1, +3, +6, and +11 (related and unrelated donor
      recipients only) or mycophenolate mofetil IV or PO every 8 hours on days 0 to +40 with taper
      to day +96 (umbilical cord blood transplant recipients only).

      After completion of study treatment, patients are followed up at 6 months, 1 year, and then
      yearly for 4 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Probability of 2-year survival in patients with myelofibrosis (MF) who receive treatment with a JAK inhibitor followed by an allogeneic transplant
time frame: At 2 years
description: The exact benchmark that will be used for comparison will be determined from the mix of Dynamic International Prognostic Scoring System (DIPSS) categories among those enrolled and treated with JAK on the current trial. From this mix, an expected two-year survival will be created as a weighted average of the data cited above. This weighted average will be used as the benchmark to which the data from the current trial will be compared.
measure: Incidence and severity of acute graft versus host disease (GVHD)
time frame: Up to 70 days post-transplant
measure: Incidence and severity of chronic GVHD
time frame: Up to 2 years
measure: Incidence of relapse
time frame: 1 year
measure: Non-relapse mortality (NRM)
time frame: Day 100
measure: Non-relapse mortality (NRM)
time frame: 1 year
measure: Overall incidence of primary graft failure/rejection
time frame: Up to 5 years
measure: Overall incidence of secondary graft failure/rejection
time frame: Up to 5 years
arm group label: Treatment (ruxolitinib, transplant)
arm group type: Experimental
description: Patients receive a ruxolitinib and undergo myeloablative or reduced-intensity conditioning followed by transplant and GVHD prophylaxis; see detailed description.
intervention type: Procedure
intervention name: Allogeneic Hematopoietic Stem Cell Transplantation
description: Undergo allogeneic hematopoietic stem cell transplant
arm group label: Treatment (ruxolitinib, transplant)
other name: Allogeneic Hematopoietic Cell Transplantation
other name: allogeneic stem cell transplantation
other name: HSC
other name: HSCT
intervention type: Drug
intervention name: Busulfan
description: Given IV
arm group label: Treatment (ruxolitinib, transplant)
other name: 1, 4-Bis[methanesulfonoxy]butane
other name: BUS
other name: Bussulfam
other name: Busulfanum
other name: Busulfex
other name: Busulphan
other name: CB 2041
other name: CB-2041
other name: Glyzophrol
other name: GT 41
other name: GT-41
other name: Joacamine
other name: Methanesulfonic Acid Tetramethylene Ester
other name: Methanesulfonic acid, tetramethylene ester
other name: Mielucin
other name: Misulban
other name: Misulfan
other name: Mitosan
other name: Myeleukon
other name: Myeloleukon
other name: Myelosan
other name: Mylecytan
other name: Myleran
other name: Sulfabutin
other name: Tetramethylene Bis(methanesulfonate)
other name: Tetramethylene bis[methanesulfonate]
other name: WR-19508
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Treatment (ruxolitinib, transplant)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Drug
intervention name: Fludarabine Phosphate
description: Given IV
arm group label: Treatment (ruxolitinib, transplant)
other name: 2-F-ara-AMP
other name: 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
other name: Beneflur
other name: Fludara
other name: SH T 586
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (ruxolitinib, transplant)
intervention type: Drug
intervention name: Melphalan
description: Given IV
arm group label: Treatment (ruxolitinib, transplant)
other name: Alanine Nitrogen Mustard
other name: CB-3025
other name: L-PAM
other name: L-Phenylalanine mustard
other name: L-Sarcolysin
other name: L-Sarcolysin Phenylalanine mustard
other name: L-Sarcolysine
other name: Melphalanum
other name: Phenylalanine Mustard
other name: Phenylalanine Nitrogen Mustard
other name: Sarcoclorin
other name: Sarkolysin
other name: WR-19813
intervention type: Drug
intervention name: Methotrexate
description: Given IV
arm group label: Treatment (ruxolitinib, transplant)
other name: Abitrexate
other name: Alpha-Methopterin
other name: Amethopterin
other name: Brimexate
other name: CL 14377
other name: CL-14377
other name: Emtexate
other name: Emthexat
other name: Emthexate
other name: Farmitrexat
other name: Fauldexato
other name: Folex
other name: Folex PFS
other name: Lantarel
other name: Ledertrexate
other name: Lumexon
other name: Maxtrex
other name: Medsatrexate
other name: Metex
other name: Methoblastin
other name: Methotrexate LPF
other name: Methotrexate Methylaminopterin
other name: Methotrexatum
other name: Metotrexato
other name: Metrotex
other name: Mexate
other name: Mexate-AQ
other name: MTX
other name: Novatrex
other name: Rheumatrex
other name: Texate
other name: Tremetex
other name: Trexeron
other name: Trixilem
other name: WR-19039
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Given IV or PO
arm group label: Treatment (ruxolitinib, transplant)
other name: Cellcept
other name: MMF
intervention type: Drug
intervention name: Ruxolitinib
description: Given PO
arm group label: Treatment (ruxolitinib, transplant)
other name: INCB-18424
other name: INCB18424
other name: Oral JAK Inhibitor INCB18424
other name: Jakafi
intervention type: Drug
intervention name: Tacrolimus
description: Given IV or PO
arm group label: Treatment (ruxolitinib, transplant)
other name: FK 506
other name: Fujimycin
other name: Hecoria
other name: Prograf
other name: Protopic
intervention type: Radiation
intervention name: Total-Body Irradiation
description: Undergo TBI
arm group label: Treatment (ruxolitinib, transplant)
other name: TOTAL BODY IRRADIATION
other name: Whole-Body Irradiation
other name: SCT_TBI
intervention type: Procedure
intervention name: Umbilical Cord Blood Transplantation
description: Undergo umbilical cord blood transplant
arm group label: Treatment (ruxolitinib, transplant)
other name: Cord Blood Transplantation
other name: UCB transplantation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rachel B. Salit
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Primary Myelofibrosis
mesh term: Mycophenolic Acid
mesh term: Cyclophosphamide
mesh term: Melphalan
mesh term: Busulfan
mesh term: Mechlorethamine
mesh term: Nitrogen Mustard Compounds
mesh term: Methotrexate
mesh term: Fludarabine
mesh term: Fludarabine phosphate
mesh term: Tacrolimus