<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/NCT03288480</url>
  </required_header>
  <id_info>
    <org_study_id>PT-112-102</org_study_id>
    <nct_id>NCT03288480</nct_id>
  </id_info>
  <brief_title>A Phase 1/2a Dose-Finding Study of PT-112 in Patients With Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>A Phase 1/2a Dose-Finding Study of PT-112 in Patients With Relapsed or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Promontory Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Promontory Therapeutics Inc.</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>
      Study PT-112-102, a multicenter, open-label dose-finding and pharmacokinetic study of PT-112&#xD;
      in patients with relapsed or refractory multiple myeloma.&#xD;
&#xD;
      This is designed as a two-part study. In the first part of the study, cohorts of three&#xD;
      patients (expanded to six patients in the event of a dose-limiting toxicity) will receive&#xD;
      escalating doses of PT-112 until the MTD is reached, based on tolerability observed during&#xD;
      the first 28 days of treatment. In the second part of the study, an expansion cohort of 14&#xD;
      patients will be treated at the recommended dose to confirm the tolerability of treatment and&#xD;
      evaluate evidence of treatment efficacy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 15, 2017</start_date>
  <completion_date type="Actual">March 1, 2021</completion_date>
  <primary_completion_date type="Actual">September 30, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a multi-center, open-label study of PT-112 in patients with relapsed or refractory MM.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recommended dose (RD) of PT-112 for further studies in patients with relapsed or refractory multiple myeloma (MM)</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration (Cmax)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-limiting toxicities (DLTs)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with Adverse Events (AEs)</measure>
    <time_frame>18 months</time_frame>
    <description>Characterization of the type, incidence, severity, duration, reversibility and relationship to treatment of adverse events (AEs), and effects on vital signs and laboratory parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response, including assessment of minimal residual disease, according to the International Myeloma Working Group (IMWG) response criteria</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship between sensitivity/response to treatment and disease status including cytogenetic biomarkers</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>PT-112</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>This is a single arm study of PT-112, which is administered to patients with relapsed or refractory MM</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PT-112</intervention_name>
    <description>This is a single arm study</description>
    <arm_group_label>PT-112</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Previously diagnosed with MM requiring treatment based on IMWG diagnostic criteria;&#xD;
&#xD;
          2. Relapsed or refractory MM after adequate exposure to and therapeutic response&#xD;
             (following IMWG response criteria) to at least one line of treatment with one or more&#xD;
             active agents, including alkylating drugs, corticosteroids, immunomodulatory drugs&#xD;
             (IMiD: thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (bortezomib,&#xD;
             cartilzomib), and monoclonal antibodies (daratumumab, elotuzumab, ixazomab);&#xD;
&#xD;
          3. Evaluable MM with at least one of the following: (a) serum monoclonal component ≥ 0.5&#xD;
             g/dL; or (b) Bence Jones (BJ) proteinuria ≥ 200 mg/24h; or (c) measurable plasmacytoma&#xD;
             (not previously irradiated); or (d) involved serum free light chain ≥ 10 mg/dL with an&#xD;
             abnormal free light chain ratio;&#xD;
&#xD;
          4. ECOG Performance Status (PS) 0-2;&#xD;
&#xD;
          5. Life expectancy &gt; 3 months;&#xD;
&#xD;
          6. At least 2 weeks (or 5 half-lives, whichever is longer) wash-out since the end of&#xD;
             previously administered experimental therapy (6 weeks if previous nitrosourea&#xD;
             containing regimen) or 2 weeks for standard-of-care regimens. Concurrent&#xD;
             corticosteroids are allowed provided they are administered at an equivalent prednisone&#xD;
             dose of ≤ 10 mg/day, as prediction or blood products only;&#xD;
&#xD;
          7. Recovery from non-hematologic toxic effects of prior therapy to grade ≤ 1 (except&#xD;
             alopecia) by NCI CTCAE Version 4.03;&#xD;
&#xD;
          8. Adequate bone marrow (BM), renal, hepatic and metabolic function.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Any of the following concomitant diseases/conditions:&#xD;
&#xD;
               -  History or presence of myocardial infarction, clinically relevant valvular heart&#xD;
                  disease, or congestive heart failure within the last 12 months;&#xD;
&#xD;
               -  Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT&#xD;
                  interval (QTc) (Fridericia) to &gt;480 msec for males or &gt;500 msec for females,&#xD;
                  based on ECG at screening (patients with stable atrial fibrillation on treatment&#xD;
                  are allowed provided they do not meet any other cardiac or prohibited drug&#xD;
                  exclusion criterion);&#xD;
&#xD;
               -  Presence of current angina;&#xD;
&#xD;
               -  Active uncontrolled infection;&#xD;
&#xD;
               -  Morphological or cytological features of myelodysplasia and/or post-chemotherapy&#xD;
                  aplasia on BM assessment;&#xD;
&#xD;
               -  Myopathy &gt; grade 2 or any clinical situation that causes significant and&#xD;
                  persistent elevation of CPK (&gt;2.5 x ULN in two different determinations performed&#xD;
                  one week apart);&#xD;
&#xD;
               -  Peripheral neuropathy &gt; grade 1, except for grade 2 without limitations on&#xD;
                  instrumental daily life activities;&#xD;
&#xD;
               -  POEMS syndrome or active plasma cell leukemia;&#xD;
&#xD;
               -  Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the&#xD;
                  control of GVHD;&#xD;
&#xD;
               -  History or presence within the last 3 months of Deep Vein Thrombosis (DVT) or a&#xD;
                  pulmonary embolism (PE);- Uncontrolled leptomeningeal disease;&#xD;
&#xD;
               -  Uncontrolled disease-related metabolic disorder (e.g., hypercalcemia);&#xD;
&#xD;
               -  Acute or chronic infections requiring systemic therapy, including, among others:&#xD;
&#xD;
               -  active infection requiring systemic therapy;&#xD;
&#xD;
               -  history of testing positive to human immunodeficiency virus (HIV) or known&#xD;
                  acquired immunodeficiency syndrome;&#xD;
&#xD;
               -  hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening&#xD;
                  (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is&#xD;
                  positive);&#xD;
&#xD;
               -  active tuberculosis (history of exposure or history of positive TB test with&#xD;
                  presence of clinical symptoms, physical or radiographic finding);&#xD;
&#xD;
               -  Any other major illness that, in the Investigator's judgment, may substantially&#xD;
                  increase the risk associated with the patient's participation in this study;&#xD;
&#xD;
          2. History of prior malignancy other than those previously treated with a curative intent&#xD;
             more than 5 years ago and without relapse (any tumor) or basal cell skin cancer, in&#xD;
             situ cervical cancer, superficial bladder cancer, or high grade intestinal polyps&#xD;
             treated adequately, regardless of the disease-free interval;&#xD;
&#xD;
          3. Prior irradiation to &gt; 30% of BM reserves (including total body irradiation),&#xD;
             regardless of the washout period;&#xD;
&#xD;
          4. High dose chemotherapy followed by autologous stem cell transplantation within 90 days&#xD;
             prior to initiating study treatment;&#xD;
&#xD;
          5. Bisphosphonate treatment within 7 days prior to initiating study treatment (while on&#xD;
             study, bisphosphonates can be administered only once a month, between Days 18 to 21 of&#xD;
             the 28-day treatment cycle)&#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>Leif Bergsagel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic Cancer Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Cancer Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Cancer Center</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology San Antonio Medical Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>April 19, 2022</last_update_submitted>
  <last_update_submitted_qc>April 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2022</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>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03288480
org study id: PT-112-102
nct id: NCT03288480
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Study PT-112-102, a multicenter, open-label dose-finding and pharmacokinetic study of PT-112
      in patients with relapsed or refractory multiple myeloma.

      This is designed as a two-part study. In the first part of the study, cohorts of three
      patients (expanded to six patients in the event of a dose-limiting toxicity) will receive
      escalating doses of PT-112 until the MTD is reached, based on tolerability observed during
      the first 28 days of treatment. In the second part of the study, an expansion cohort of 14
      patients will be treated at the recommended dose to confirm the tolerability of treatment and
      evaluate evidence of treatment efficacy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a multi-center, open-label study of PT-112 in patients with relapsed or refractory MM.
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended dose (RD) of PT-112 for further studies in patients with relapsed or refractory multiple myeloma (MM)
time frame: 18 months
measure: Peak Plasma Concentration (Cmax)
time frame: 18 months
measure: Area under the plasma concentration versus time curve (AUC)
time frame: 18 months
measure: Dose-limiting toxicities (DLTs)
time frame: 18 months
measure: Number of patients with Adverse Events (AEs)
time frame: 18 months
description: Characterization of the type, incidence, severity, duration, reversibility and relationship to treatment of adverse events (AEs), and effects on vital signs and laboratory parameters.
measure: Tumor response, including assessment of minimal residual disease, according to the International Myeloma Working Group (IMWG) response criteria
time frame: 18 months
measure: Duration of response
time frame: 18 months
measure: Progression free survival
time frame: 18 months
measure: Relationship between sensitivity/response to treatment and disease status including cytogenetic biomarkers
time frame: 18 months
arm group label: PT-112
arm group type: Other
description: This is a single arm study of PT-112, which is administered to patients with relapsed or refractory MM
intervention type: Drug
intervention name: PT-112
description: This is a single arm study
arm group label: PT-112
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Leif Bergsagel, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
sharing ipd: Undecided