<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/NCT02973711</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2015.103</org_study_id>
    <secondary_id>HUM00122063</secondary_id>
    <nct_id>NCT02973711</nct_id>
  </id_info>
  <brief_title>A Study of Ruxolitinib in Combination With Nilotinib in Patients With Chronic Phase CML</brief_title>
  <official_title>A Phase I/II Study of Ruxolitinib in Combination With Nilotinib in Patients With Chronic Phase CML Who Have Achieved a Complete Hematologic Remission, Complete Cytogenetic Remission, and Major Molecular Remission, But Not a Complete Molecular Remission on a Tyrosine Kinase Inhibitor Alone.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel 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 study combines two drugs (ruxolitinib and the tyrosine kinase inhibitor, nilotinib) in&#xD;
      an attempt to eliminate the CML (Chronic Myeloid Leukemia) stem cell population and thus&#xD;
      allow for the deepest and most durable response possible in patients with CML in chronic&#xD;
      phase who have achieved a complete hematologic remission (CHR), complete cytogenetic&#xD;
      remission (CCyR), and major molecular remission (MMR), but not a complete molecular remission&#xD;
      (CMR). The study will look at safety and tolerability of ruxolitinib when combined with&#xD;
      nilotinib in a phase I study and will help establish the MTD (Maximum Tolerated Dose) of&#xD;
      ruxolitinib when combined with nilotinib. Once the optimal dose of ruxolitinib is established&#xD;
      in the phase I setting, a phase II evaluation will seek to establish the efficacy of this&#xD;
      combination.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    lack of funding&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 2018</start_date>
  <completion_date type="Anticipated">August 2021</completion_date>
  <primary_completion_date type="Anticipated">August 2021</primary_completion_date>
  <phase>Phase 1/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>Maximum Tolerated Dose (MTD) of ruxolitinib when combined with nilotinib</measure>
    <time_frame>2 Years</time_frame>
    <description>Maximum Tolerated Dose (MTD) of ruxolitinib when combined with nilotinib</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The number of patients that achieve a Complete Molecular Response (CMR)</measure>
    <time_frame>2 Years</time_frame>
    <description>CMR is defined as an absence of the BCR-ABL1 transcript by qPCR performed on peripheral blood or bone marrow aspirate.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Leukemia, Chronic Myeloid</condition>
  <arm_group>
    <arm_group_label>Nilotinib + Ruxolitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The first part of the trial will be Phase I and will enroll 25 participants. Participants will receive nilotinib BID and either 10, 15 or 20 mg of ruxolitinib BID. Maximum tolerated dose (MTD) of ruxolitinib will be determined.&#xD;
The second part of the trial will be a Phase II and will enroll 25 subjects. Participants will receive nilotinib and the MTD of ruxolitinib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nilotinib</intervention_name>
    <description>Nilotinib 300 mg BID</description>
    <arm_group_label>Nilotinib + Ruxolitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Ruxolitinib, 10, 15 or 20mg BID</description>
    <arm_group_label>Nilotinib + Ruxolitinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ≥ 18 years of age&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Oncology Group) Performance Status 0, 1, or 2&#xD;
&#xD;
          -  Must have a diagnosis of Philadelphia chromosome positive (Ph+) chronic myeloid&#xD;
             leukemia (CML) in chronic phase, with no previous evidence of accelerated or&#xD;
             blast-phase disease.&#xD;
&#xD;
          -  Must be actively receiving treatment for their CML with a tyrosine kinase inhibitor&#xD;
             (TKI): imatinib, dasatinib, nilotinib or bosutinib, and must be on stable dose for &gt; 1&#xD;
             year.&#xD;
&#xD;
          -  Must have an ongoing complete hematologic response (CHR) on a TKI&#xD;
&#xD;
          -  Must have an ongoing complete cytogenetic response (CCyR) on a TKI&#xD;
&#xD;
          -  Must be in a major molecular remission (MMR) on a TKI for a minimum of 1 year leading&#xD;
             up to enrollment.&#xD;
&#xD;
          -  Adequate end organ function&#xD;
&#xD;
          -  Adequate electrolytes&#xD;
&#xD;
          -  Adequate platelet count&#xD;
&#xD;
          -  Adequate neutrophil count&#xD;
&#xD;
          -  Written informed consent prior to any screening procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients in complete molecular remission (CMR) on a TKI.&#xD;
&#xD;
          -  Patients who have failed nilotinib or not tolerated nilotinib in the past&#xD;
&#xD;
          -  Certain cardiovascular disorders&#xD;
&#xD;
          -  Currently receiving treatment with strong CYP3A4 inhibitors which cannot be&#xD;
             discontinued prior to starting study drug&#xD;
&#xD;
          -  Actively receiving herbal medicines that are strong CYP3A4 inhibitors and/or inducers&#xD;
             and treatment cannot be discontinued prior to starting study drug&#xD;
&#xD;
          -  Currently receiving treatment with any medications that have the potential to prolong&#xD;
             the QT interval that cannot be discontinued prior to starting study drug&#xD;
&#xD;
          -  Impaired gastrointestinal (GI) function or GI disease that may significantly alter the&#xD;
             absorption of the drug&#xD;
&#xD;
          -  Acute or chronic pancreatic disease within the last year&#xD;
&#xD;
          -  Cytopathologically confirmed Central Nervous System (CNS) infiltration&#xD;
&#xD;
          -  Another primary malignancy that requires systemic chemotherapy or radiation&#xD;
&#xD;
          -  Acute or chronic liver disease or severe renal disease considered unrelated to the&#xD;
             cancer&#xD;
&#xD;
          -  History of significant congenital or acquired bleeding disorder unrelated to cancer&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered&#xD;
             from prior surgery&#xD;
&#xD;
          -  Past treatment with ruxolitinib&#xD;
&#xD;
          -  Treatment with other investigational agent within 30 days of Day 1&#xD;
&#xD;
          -  Inability to grant consent or history of non-compliance to medical regimens&#xD;
&#xD;
          -  Women who are breastfeeding&#xD;
&#xD;
          -  Women of child-bearing potential, unless they are using highly effective contraception&#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>Patrick Burke, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>February 11, 2021</last_update_submitted>
  <last_update_submitted_qc>February 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2021</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>Leukemia, Myeloid, Chronic-Phase</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
  </condition_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/NCT02973711
org study id: UMCC 2015.103
secondary id: HUM00122063
nct id: NCT02973711
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study combines two drugs (ruxolitinib and the tyrosine kinase inhibitor, nilotinib) in
      an attempt to eliminate the CML (Chronic Myeloid Leukemia) stem cell population and thus
      allow for the deepest and most durable response possible in patients with CML in chronic
      phase who have achieved a complete hematologic remission (CHR), complete cytogenetic
      remission (CCyR), and major molecular remission (MMR), but not a complete molecular remission
      (CMR). The study will look at safety and tolerability of ruxolitinib when combined with
      nilotinib in a phase I study and will help establish the MTD (Maximum Tolerated Dose) of
      ruxolitinib when combined with nilotinib. Once the optimal dose of ruxolitinib is established
      in the phase I setting, a phase II evaluation will seek to establish the efficacy of this
      combination.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) of ruxolitinib when combined with nilotinib
time frame: 2 Years
description: Maximum Tolerated Dose (MTD) of ruxolitinib when combined with nilotinib
measure: The number of patients that achieve a Complete Molecular Response (CMR)
time frame: 2 Years
description: CMR is defined as an absence of the BCR-ABL1 transcript by qPCR performed on peripheral blood or bone marrow aspirate.
arm group label: Nilotinib + Ruxolitinib
arm group type: Experimental
description: The first part of the trial will be Phase I and will enroll 25 participants. Participants will receive nilotinib BID and either 10, 15 or 20 mg of ruxolitinib BID. Maximum tolerated dose (MTD) of ruxolitinib will be determined.
The second part of the trial will be a Phase II and will enroll 25 subjects. Participants will receive nilotinib and the MTD of ruxolitinib.
intervention type: Drug
intervention name: Nilotinib
description: Nilotinib 300 mg BID
arm group label: Nilotinib + Ruxolitinib
intervention type: Drug
intervention name: Ruxolitinib
description: Ruxolitinib, 10, 15 or 20mg BID
arm group label: Nilotinib + Ruxolitinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrick Burke, M.D.
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia, Myeloid, Chronic-Phase
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive