<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/NCT03786926</url>
  </required_header>
  <id_info>
    <org_study_id>2018-689-00US1</org_study_id>
    <nct_id>NCT03786926</nct_id>
  </id_info>
  <brief_title>Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas</brief_title>
  <official_title>A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-689 in Patients With Relapsed or Refractory Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hutchmed</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hutchmed</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>
      An open-label, dose escalation and expansion clinical trial to evaluate the safety,&#xD;
      tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients&#xD;
      with relapsed or refractory lymphoma.&#xD;
&#xD;
      HMPL-689 is a selective and potent small molecule inhibitor targeting the isoform&#xD;
      phosphoinositide 3'-kinase delta (PI3Kδ), a key component in the B-cell receptor signaling&#xD;
      pathway&#xD;
&#xD;
      This study will consist of a dose escalation stage (Stage 1) and a dose expansion stage&#xD;
      (Stage 2).&#xD;
&#xD;
      Dose Escalation Stage (Stage 1):&#xD;
&#xD;
      This stage will end when any of the following criteria is met:&#xD;
&#xD;
        -  The dose level 1 demonstrates an excessive toxicity, ie, 3 dose limiting toxicities&#xD;
           (DLTs) are observed out of the first 3 patients at dose level 1.&#xD;
&#xD;
        -  The maximum sample size is reached.&#xD;
&#xD;
        -  The MTD and/or RP2D is confirmed.&#xD;
&#xD;
      Dose Expansion Stage (Stage 2):&#xD;
&#xD;
      To further characterize the safety and explore the preliminary anti-tumor activity of&#xD;
      HMPL-689 at RP2D, patients with B cell lymphoma will be enrolled in the dose expansion stage.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 26, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of adverse events as evaluated by the NCI CTCAE v5.0 grade</measure>
    <time_frame>From first dose to within 30 days after last dose</time_frame>
    <description>The safety and tolerability of HMPL-689 dose will be evaluated based on adverse events data</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>maximum plasma concentration (Cmax)</measure>
    <time_frame>from cycle 1 day 1 30 min pre-dose until cycle 2 day 1 30 min pre dose (escalation) from cycle 1 day 1 30 min pre-dose to Cycle 5 day 1 pre-dose 30 min (expansion) (cycle is 28 days)</time_frame>
    <description>To characterize the pharmacokinetic (PK) properties of HMPL-689 in patients with relapsed or refractory lymphoma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve in a selected time interval (AUC0-t)</measure>
    <time_frame>from cycle 1 day 1 30 min pre-dose until cycle 2 day 1 30 min pre dose (escalation) from cycle 1 day 1 30 min pre-dose to Cycle 5 day 1 pre-dose 30 min (expansion) (cycle is 28 days)</time_frame>
    <description>To characterize the pharmacokinetic (PK) properties of HMPL-689 in patients with relapsed or refractory lymphoma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) defined as the proportion of patients who have a CR or PR</measure>
    <time_frame>from first dose to within 30 days of last dose</time_frame>
    <description>To evaluate the anti-tumor activity of HMPL-689 in patients with relapsed or refractory lymphoma according to: (1) Chronic Lymphocytic Leukemia (CLL) - modified International Workshop on CLL guidelines, (2) Waldenstrom's Macroglobulinemia (WM) - consensus of international workshops on WM, (3) Lymphomas other than CLL or WM: Lugano Response Criteria for Hodgkin and Non-Hodgkin's Lymphoma</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients take HMPL-689 taken daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HMPL-689</intervention_name>
    <description>HMPL-689 is a PI3Kδ inhibitor</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. (ECOG) performance status of 0 or 1;&#xD;
&#xD;
          2. Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade&#xD;
             1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);&#xD;
&#xD;
          3. Patients with relapsed or refractory NHL for whom:&#xD;
&#xD;
               -  Standard of care treatment options no longer exist (Stage 1 only);&#xD;
&#xD;
               -  Standard of care treatment options no longer exist with the exception of&#xD;
                  PI3K-delta inhibitors (Stage 2 only);&#xD;
&#xD;
          4. Expected survival of more than 24 weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients who meet any of the following criteria will be excluded from study entry:&#xD;
&#xD;
          1. Primary central nervous system (CNS) lymphoma;&#xD;
&#xD;
          2. Any of the following laboratory abnormalities Absolute neutrophil count; &lt;1.0×10^9/L,&#xD;
             Hemoglobin &lt;80 g/L Platelets &lt;50 ×10^9/L&#xD;
&#xD;
          3. Inadequate organ function, defined by the following:&#xD;
&#xD;
               -  Total bilirubin ≥1.5 times the upper limit of normal (× ULN);&#xD;
&#xD;
               -  AST or ALT &gt; 2.5 × ULN;&#xD;
&#xD;
               -  Estimated creatinine clearance (CrCl) per Cockcroft-Gault;&#xD;
&#xD;
               -  Dose Escalation stage of trial (Stage 1) - CrCl &lt; 40 mL/min;&#xD;
&#xD;
               -  Dose Expansion stage of trial (Stage 2) - CrCl &lt;30 mL/min;&#xD;
&#xD;
          4. International normalized ratio (INR) &gt; 1.5 × ULN, activated partial thromboplastin&#xD;
             time (aPTT) &gt; 1.5 × ULN;&#xD;
&#xD;
          5. Serum amylase or lipase &gt; ULN at screening or known medical history of serum amylase&#xD;
             or lipase &gt; ULN;&#xD;
&#xD;
          6. Patients with presence of second primary malignant tumors within the last 2 years;&#xD;
&#xD;
          7. Clinically significant history of liver disease;&#xD;
&#xD;
          8. Prior treatment with any PI3Kδ inhibitors;&#xD;
&#xD;
          9. Any prior use of the following: cancer therapy within 3 weeks of study treatment, GCSF&#xD;
             within 7 days of screening, steroid therapy or targeted anti-neoplastic intent within&#xD;
             7 days of treatment, any use of strong CYP3A4 inducers within 2 weeks prior to&#xD;
             initiation of study treatment, prior autologous transplant within 6 months of study&#xD;
             treatment, prior allogenic stem cell transplant within 6 months of study treatment;&#xD;
&#xD;
         10. Clinically significant active infection or interstitial lung diseases (including drug&#xD;
             induced pneumonitis);&#xD;
&#xD;
         11. Major surgical procedure within 4 weeks prior to initiation of study treatment;&#xD;
&#xD;
         12. Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less&#xD;
             than or equal to 1, except for alopecia;&#xD;
&#xD;
         13. New York Heart Association (NYHA) Class II or greater congestive heart failure;&#xD;
&#xD;
         14. Congenital long QT syndrome or QTc &gt;470 msec;&#xD;
&#xD;
         15. Currently use medication known to cause QT prolongation or torsades de pointes;&#xD;
&#xD;
         16. History of myocardial infarction or unstable angina within 6 months prior to&#xD;
             initiation of study treatment;&#xD;
&#xD;
         17. History of stroke or transient ischemic attack within 6 months prior to initiation of&#xD;
             study treatment;&#xD;
&#xD;
         18. Inability to take oral medication, prior surgical procedures affecting absorption, or&#xD;
             active peptic ulcer disease;&#xD;
&#xD;
         19. History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);&#xD;
&#xD;
         20. Patients with ongoing chronic gastrointestinal diseases;&#xD;
&#xD;
         21. Any other diseases, metabolic dysfunction, physical examination finding, or clinical&#xD;
             laboratory finding that, in the investigator's opinion, gives reasonable suspicion of&#xD;
             a disease or condition that contraindicates the use of an investigational drug or that&#xD;
             may affect the interpretation of the results or renders the patient at high risk from&#xD;
             treatment complications.&#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>Vijay Jayaprakash, MD</last_name>
    <role>Study Director</role>
    <affiliation>Hutchison Medipharma Limited</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nilanjan Ghosh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Atrium Health Levine Cancer Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jonathan B Cohen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory Winship Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Cancer Medical Center</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ventura County Hematology-Oncology Specialists</name>
      <address>
        <city>Oxnard</city>
        <state>California</state>
        <zip>93030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute of Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Alliance, Inc</name>
      <address>
        <city>Westbury</city>
        <state>New York</state>
        <zip>11590</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute- Atrium Health</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott and White Research Institute</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renovatio Clinical</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77339</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology Associates, P.S.</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsingin yliopistollinen keskussairaala</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tampereen yliopistollinen sairaala</name>
      <address>
        <city>Tampere</city>
        <zip>33520</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Henri Mondor</name>
      <address>
        <city>Créteil Cedex</city>
        <state>Val De Marne</state>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes - Hotel Dieu</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Bordeaux - Hôpital Haut-Lévêque</name>
      <address>
        <city>Pessac</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KO-MED Centra Kliniczne</name>
      <address>
        <city>Biała Podlaska</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne</name>
      <address>
        <city>Gdańsk</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BioResearch Group Sp. Z. o. o.</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NASZ LEKARZ Osrodek Badan Klinicznych</name>
      <address>
        <city>Toruń</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego</name>
      <address>
        <city>Wroclaw</city>
        <zip>50-566</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO Badalona - Hospital Universitari Germans Trias i Pujol</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO l'Hospitalet - Hospital Duran i Reynals</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Seville</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena</name>
      <address>
        <city>Seville</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
    <country>France</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Denmark</country>
  </removed_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 23, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>January 11, 2023</last_update_submitted>
  <last_update_submitted_qc>January 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CLL</keyword>
  <keyword>SLL</keyword>
  <keyword>FL</keyword>
  <keyword>MZL</keyword>
  <keyword>LPL</keyword>
  <keyword>WM</keyword>
  <keyword>MCL</keyword>
  <keyword>PTCL</keyword>
  <keyword>CBCL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</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/NCT03786926
org study id: 2018-689-00US1
nct id: NCT03786926
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
An open-label, dose escalation and expansion clinical trial to evaluate the safety,
      tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas
This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients
      with relapsed or refractory lymphoma.

      HMPL-689 is a selective and potent small molecule inhibitor targeting the isoform
      phosphoinositide 3'-kinase delta (PI3Kδ), a key component in the B-cell receptor signaling
      pathway

      This study will consist of a dose escalation stage (Stage 1) and a dose expansion stage
      (Stage 2).

      Dose Escalation Stage (Stage 1):

      This stage will end when any of the following criteria is met:

        -  The dose level 1 demonstrates an excessive toxicity, ie, 3 dose limiting toxicities
           (DLTs) are observed out of the first 3 patients at dose level 1.

        -  The maximum sample size is reached.

        -  The MTD and/or RP2D is confirmed.

      Dose Expansion Stage (Stage 2):

      To further characterize the safety and explore the preliminary anti-tumor activity of
      HMPL-689 at RP2D, patients with B cell lymphoma will be enrolled in the dose expansion stage.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of adverse events as evaluated by the NCI CTCAE v5.0 grade
time frame: From first dose to within 30 days after last dose
description: The safety and tolerability of HMPL-689 dose will be evaluated based on adverse events data
measure: maximum plasma concentration (Cmax)
time frame: from cycle 1 day 1 30 min pre-dose until cycle 2 day 1 30 min pre dose (escalation) from cycle 1 day 1 30 min pre-dose to Cycle 5 day 1 pre-dose 30 min (expansion) (cycle is 28 days)
description: To characterize the pharmacokinetic (PK) properties of HMPL-689 in patients with relapsed or refractory lymphoma
measure: Area under the concentration-time curve in a selected time interval (AUC0-t)
time frame: from cycle 1 day 1 30 min pre-dose until cycle 2 day 1 30 min pre dose (escalation) from cycle 1 day 1 30 min pre-dose to Cycle 5 day 1 pre-dose 30 min (expansion) (cycle is 28 days)
description: To characterize the pharmacokinetic (PK) properties of HMPL-689 in patients with relapsed or refractory lymphoma
measure: Objective response rate (ORR) defined as the proportion of patients who have a CR or PR
time frame: from first dose to within 30 days of last dose
description: To evaluate the anti-tumor activity of HMPL-689 in patients with relapsed or refractory lymphoma according to: (1) Chronic Lymphocytic Leukemia (CLL) - modified International Workshop on CLL guidelines, (2) Waldenstrom's Macroglobulinemia (WM) - consensus of international workshops on WM, (3) Lymphomas other than CLL or WM: Lugano Response Criteria for Hodgkin and Non-Hodgkin's Lymphoma
arm group label: Treatment
arm group type: Experimental
description: All patients take HMPL-689 taken daily
intervention type: Drug
intervention name: HMPL-689
description: HMPL-689 is a PI3Kδ inhibitor
arm group label: Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Vijay Jayaprakash, MD
role: Study Director
affiliation: Hutchison Medipharma Limited
last name: Nilanjan Ghosh, MD
role: Principal Investigator
affiliation: Atrium Health Levine Cancer Institute
last name: Jonathan B Cohen, MD
role: Principal Investigator
affiliation: Emory Winship Cancer Institute
facility: 
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country: Finland
country: France
country: Italy
country: Poland
country: Spain
country: United States
country: Denmark
responsible party type: Sponsor
mesh term: Lymphoma
sharing ipd: No