<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/NCT02992483</url>
  </required_header>
  <id_info>
    <org_study_id>CMIK665X2101</org_study_id>
    <secondary_id>2016-003624-22</secondary_id>
    <nct_id>NCT02992483</nct_id>
  </id_info>
  <brief_title>Phase I Study of MIK665, a Mcl-1 Inhibitor, in Patients With Refractory or Relapsed Lymphoma or Multiple Myeloma</brief_title>
  <official_title>Phase I Open Label, Multi-center Study to Characterize the Safety, Tolerability and Pharmacokinetics of Intravenously Administered MIK665, a Mcl-1 Inhibitor, in Patients With Refractory or Relapsed Lymphoma or Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</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>
      The purpose of this first in human study is to assess safety, tolerability, PK and&#xD;
      preliminary clinical activity and to estimate the MTD(s)/RDE(s) of MIK665 (also referred as&#xD;
      S64315) as single agent administered intravenously (i.v.) in adult patients with refractory&#xD;
      or relapsed lymphoma or multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The design of this phase I, open label, dose finding study was chosen in order to&#xD;
      characterize the safety and tolerability of MIK665 and to determine the Maximal Tolerated&#xD;
      Dose(s) (MTD(s)) and/or Recommended Dose(s) for Expansion (RDE(s)).&#xD;
&#xD;
      This study will utilize a Bayesian Hierarchical model to guide dose escalation and estimate&#xD;
      the MTD(s) based on the dose-DLT relationship(s) for MIK665 in the indications.&#xD;
&#xD;
      The expansion part of the study will employ an open-label multiple arm design. The purpose of&#xD;
      the expansion part is to further assess safety, tolerability, PK, PD and the anti-tumor&#xD;
      activity of MIK665 at the selected RDE/s for Multiple Myeloma (MM) and MYC positive Diffuse&#xD;
      large B-Cell Lymphoma (DLBCL) identified in the dose-escalation part.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 12, 2017</start_date>
  <completion_date type="Actual">June 7, 2019</completion_date>
  <primary_completion_date type="Actual">June 7, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and severity of AEs and SAEs, incl. changes in laboratory parameters, vital signs and ECGs.</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of DLTs during the first cycle of treatment with single agent MIK665 during the dose escalation phase only</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tolerability: Dose interruptions</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tolerability: Dose reductions</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tolerability: Dose intensity</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best Overall response (BOR) per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under Curve (AUC)</measure>
    <time_frame>2 years</time_frame>
    <description>Plasma PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>2 years</time_frame>
    <description>Plasma PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life (T1/2)</measure>
    <time_frame>2 years</time_frame>
    <description>Plasma PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution (Vz)</measure>
    <time_frame>2 years</time_frame>
    <description>Plasma PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL)</measure>
    <time_frame>2 years</time_frame>
    <description>Plasma PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Multiple Myeloma (MM), Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma</condition>
  <arm_group>
    <arm_group_label>MIK665</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MIK665</intervention_name>
    <description>MIK665</description>
    <arm_group_label>MIK665</arm_group_label>
    <other_name>S64315</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Histologically confirmed lymphoma (WHO classification), or confirmed MM (IMWG), that&#xD;
             is relapsed and/or refractory.&#xD;
&#xD;
          -  Other Inclusion Criteria May Apply.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Known history of chronic liver disease&#xD;
&#xD;
          -  History of chronic pancreatitis.&#xD;
&#xD;
          -  Prior treatment with Mcl-1 inhibitor.&#xD;
&#xD;
          -  Other Exclusion Criteria May Apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>MD Anderson Cancer Center/University of Texas MD Anderson CC</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nantes Cedex 1</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rozzano</city>
        <state>MI</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fukuoka-city</city>
        <state>Fukuoka</state>
        <zip>811-1395</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Salamanca</city>
        <state>Castilla Y Leon</state>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Korea, Republic of</country>
  </removed_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17854</url>
    <description>Study Results</description>
  </link>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>December 12, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>July 27, 2021</last_update_submitted>
  <last_update_submitted_qc>July 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>multiple myeloma</keyword>
  <keyword>lymphoma</keyword>
  <keyword>dlbcl</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</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/NCT02992483
org study id: CMIK665X2101
secondary id: 2016-003624-22
nct id: NCT02992483
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this first in human study is to assess safety, tolerability, PK and
      preliminary clinical activity and to estimate the MTD(s)/RDE(s) of MIK665 (also referred as
      S64315) as single agent administered intravenously (i.v.) in adult patients with refractory
      or relapsed lymphoma or multiple myeloma.
The design of this phase I, open label, dose finding study was chosen in order to
      characterize the safety and tolerability of MIK665 and to determine the Maximal Tolerated
      Dose(s) (MTD(s)) and/or Recommended Dose(s) for Expansion (RDE(s)).

      This study will utilize a Bayesian Hierarchical model to guide dose escalation and estimate
      the MTD(s) based on the dose-DLT relationship(s) for MIK665 in the indications.

      The expansion part of the study will employ an open-label multiple arm design. The purpose of
      the expansion part is to further assess safety, tolerability, PK, PD and the anti-tumor
      activity of MIK665 at the selected RDE/s for Multiple Myeloma (MM) and MYC positive Diffuse
      large B-Cell Lymphoma (DLBCL) identified in the dose-escalation part.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence and severity of AEs and SAEs, incl. changes in laboratory parameters, vital signs and ECGs.
time frame: 2 years
measure: Incidence of DLTs during the first cycle of treatment with single agent MIK665 during the dose escalation phase only
time frame: 2 years
measure: Tolerability: Dose interruptions
time frame: 2 years
measure: Tolerability: Dose reductions
time frame: 2 years
measure: Tolerability: Dose intensity
time frame: 2 years
measure: Best Overall response (BOR) per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma
time frame: 2 years
measure: Area Under Curve (AUC)
time frame: 2 years
description: Plasma PK parameter
measure: Maximum Plasma Concentration (Cmax)
time frame: 2 years
description: Plasma PK parameter
measure: Terminal elimination half-life (T1/2)
time frame: 2 years
description: Plasma PK parameter
measure: Apparent volume of distribution (Vz)
time frame: 2 years
description: Plasma PK parameter
measure: Clearance (CL)
time frame: 2 years
description: Plasma PK parameter
measure: Duration of Response (DOR)per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma
time frame: 2 years
measure: Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma
time frame: 2 years
arm group label: MIK665
arm group type: Experimental
intervention type: Drug
intervention name: MIK665
description: MIK665
arm group label: MIK665
other name: S64315
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: France
country: Germany
country: Italy
country: Japan
country: Spain
country: United States
country: Korea, Republic of
url: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17854
description: Study Results
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
sharing ipd: No