<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/NCT03779113</url>
  </required_header>
  <id_info>
    <org_study_id>2018-523-00US1</org_study_id>
    <nct_id>NCT03779113</nct_id>
  </id_info>
  <brief_title>An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma</brief_title>
  <official_title>A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 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>
      This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients&#xD;
      with relapsed or refractory lymphoma who have exhausted approved therapy options. This study&#xD;
      consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients&#xD;
      with relapsed or refractory lymphoma who have exhausted approved therapy options. This study&#xD;
      consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2).&#xD;
&#xD;
      Dose Escalation Stage (Stage 1)&#xD;
&#xD;
      Dosing will begin at 100 mg once daily (QD). A cycle of study treatment will be defined as 28&#xD;
      days of continuous dosing. The modified 3+3 design will be applied for dose escalation and&#xD;
      MTD determination to limit the number of patients exposed to potentially ineffective or&#xD;
      unsafe doses. The study will enroll 1 patient and the patient will be treated for a 28-day&#xD;
      cycle in the initial dose cohort. If there is no Dose Limiting Toxicity (DLT) and no more&#xD;
      than 2 treatment-emergent adverse events (TEAEs) of Common Terminology Criteria for Adverse&#xD;
      Events (CTCAE) Grade ≥2 in the first treatment cycle, the study will be escalated to the next&#xD;
      dose cohort and continue with the standard 3+3 design. Otherwise, the trial will revert to a&#xD;
      standard 3+3 design from the initial dose cohort. A minimum of 3 patients will be enrolled&#xD;
      and observed for toxicity in each successive dose cohort after the initial dose cohort. If&#xD;
      the 3 patients initially enrolled in a given dose cohort complete the DLT assessment window&#xD;
      (Cycle 1, Days 1-28) without experiencing a DLT, 3 patients will be enrolled at the next&#xD;
      higher dose level. If 2 or more of the initial 3 patients enrolled at any dose level&#xD;
      experience a DLT during the DLT assessment window, the dose escalation will be halted. If 1&#xD;
      of the initial 3 patients enrolled at any dose level experiences a DLT during the DLT&#xD;
      assessment window, additional patients will be enrolled at that dose level for a minimum of 6&#xD;
      evaluable patients for DLT. If a DLT is observed in 1 of the 6 valuable patients at this dose&#xD;
      level, dose escalation will proceed to the next pre- defined dose level. If DLTs are observed&#xD;
      in 2 or more of the 6 evaluable patients at a given dose level, the dose escalation will be&#xD;
      halted. If the dose escalation is completed due to 2 or more DLTs at a dose level and that&#xD;
      dose level is ≥50% higher than the previous dose level, then an intermediate dose level may&#xD;
      be evaluated for toxicity in the same manner as described above. If the dose level is &lt;50%&#xD;
      higher than the previous dose level, in which only 3 DLT evaluable patients were enrolled, 3&#xD;
      additional patients will be enrolled at that dose level to comprise 6 DLT evaluable patients.&#xD;
&#xD;
      The proposed dose escalation scheme comprises Cohorts 1 to 5 with dosing levels of 100 mg QD,&#xD;
      200 mg QD, 400 mg QD, 600 mg QD and 800 mg QD, respectively. The need for dose escalation&#xD;
      beyond 800 mg QD, the specific dose to be tested and the potential for twice-daily (BID)&#xD;
      dosing will be evaluated jointly by investigators and the sponsor based on the cumulative&#xD;
      clinical safety, pharmacokinetic, and preliminary efficacy data. Safety monitoring and&#xD;
      evaluation of dose escalation will be carried out by the Safety Review Committee, which will&#xD;
      be comprised of the sponsor's study team members (including medical monitor, safety monitor&#xD;
      and and Pharmacokinetic scientist) and the site principal investigators. The adverse event&#xD;
      profile and serum concentration of HMPL-523 data will be evaluated to determine whether it is&#xD;
      safe to continue the assigned HMPL-523 dose for dose escalation or whether the dose should be&#xD;
      de-escalated to the lower dose level.&#xD;
&#xD;
      Dose Expansion Stage (Stage 2)&#xD;
&#xD;
      The adverse event profile, serum concentration, and preliminary anti-tumor activity of&#xD;
      HMPL-523 at the maximum tolerated dose(MTD)/recommended phase 2 dose(RP2D) will be further&#xD;
      evaluated in approximately 50 patients with relapsed or refractory indolent B-cell&#xD;
      non-Hodgkin's lymphomas. The tumor types of the dose expansion stage are restricted to:&#xD;
&#xD;
        -  10 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma&#xD;
&#xD;
        -  20 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma post-BTK&#xD;
           exposure&#xD;
&#xD;
        -  10 patients with mantle cell lymphoma&#xD;
&#xD;
        -  20 patients with follicular lymphoma (Grade 1-3a)&#xD;
&#xD;
        -  10 patients with marginal zone lymphoma&#xD;
&#xD;
        -  10 patients with waldenström's macroglobulinemia/lymphoplasmacytic lymphoma&#xD;
&#xD;
        -  10 patients with peripheral T- cell lymphoma&#xD;
&#xD;
        -  10 patients with cutaneous B-cell lymphoma&#xD;
&#xD;
        -  10 patients with hodgkin lymphoma&#xD;
&#xD;
      Patients will receive HMPL-523 at the MTD/RP2D for continuous 28-day treatment cycles until&#xD;
      disease progression, death, intolerable toxicity, at investigator's discretion that the&#xD;
      patient can no longer benefit from the study treatment, patient withdrawal from the study, or&#xD;
      the end of study, whichever comes first.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 26, 2019</start_date>
  <completion_date type="Anticipated">January 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 1</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>Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0</measure>
    <time_frame>From first dose to within 30 days after the last dose</time_frame>
    <description>The safety and tolerability of HMPL-523 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, 5 min pre-dose 1st dose until Cycle 1, Day 28 8 hours post-dose.</time_frame>
    <description>To Characterize the pharmacokinetic properties of HMPL-523 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, 5 min pre-dose 1st dose until Cycle 1, Day 28 8 hours post-dose.</time_frame>
    <description>To characterize the pharmacokinetic properties of HMPL-523 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 after the last dose</time_frame>
    <description>To evaluate the anti-tumor activity of HMPL-523 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="Anticipated">140</enrollment>
  <condition>Non Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients to received study drug (HMPL-523)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HMPL-523</intervention_name>
    <description>Oral HMPL-523</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must meet the following criteria to be eligible for study entry:&#xD;
&#xD;
          1. Signed informed consent form (ICF).&#xD;
&#xD;
          2. Age ≥18 years.&#xD;
&#xD;
          3. ECOG performance status of 0 or 1.&#xD;
&#xD;
          4. Histologically confirmed lymphoma, including Hodgkin's lymphoma and non-Hodgkin's&#xD;
             lymphoma. In the dose expansion stage, the tumor types may be restricted to any or all&#xD;
             of the following tumor types. There may be approximately 10 patients in each cohort&#xD;
             depending on response signals suggesting efficacy, except for 2 identified cohorts&#xD;
             with approximately 20 patients per cohort: relapsed or refractory CLL/SLL, CLL/SLL&#xD;
             post-BTK exposure (n=20), MCL, FL (Grade 1-3a) (n=20), MZL, WM/LPL, PTCL,CBCL, and/or&#xD;
             HL&#xD;
&#xD;
          5. Patients with relapsed or refractory lymphoma who have exhausted all approved therapy&#xD;
             options.&#xD;
&#xD;
          6. In the dose expansion stage, patients must have measurable disease for an objective&#xD;
             response assessment, except for patients with CLL and WM/LPL&#xD;
&#xD;
          7. Availability of tumor sample for patients in dose expansion cohorts: This may be an&#xD;
             archival tissue sample obtained after most recent therapy or a fresh biopsy; if tumor&#xD;
             sample is not available, the Sponsor may waive the requirement after discussion&#xD;
&#xD;
          8. Expected survival of more than 24 weeks as determined by the investigator.&#xD;
&#xD;
          9. Male patients must agree to use a condom and female patients of childbearing potential&#xD;
             must agree to use highly effective contraceptive measures for 30 days after the last&#xD;
             dose of study drug. These include as combined hormonal contraception associated with&#xD;
             inhibition of ovulation (oral, intravaginal, and transdermal), progestogen-only&#xD;
             hormonal contraception associated with inhibition of ovulation (oral, injectable, and&#xD;
             implantable), intrauterine contraceptive device, intrauterine hormone release system,&#xD;
             bilateral tubal occlusion, or a vasectomized partner, provided that male partner is&#xD;
             the sole sexual partner of the female patient. Postmenopausal females (women who have&#xD;
             not had menses for at least 1 year without an alternative medical cause) are exempt&#xD;
             from this criterion.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Patients with 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: Total bilirubin &gt;1.5 times the&#xD;
             upper limit of normal (× ULN), aspartate aminotransferase and/or alanine&#xD;
             aminotransferase &gt;2.5 × ULN, Estimated Creatinine Clearance (CrCl) per Cockcroft-Gault&#xD;
             [Dose Escalation portion of trial (Stage 1) CrCl &lt; 40 mL/min, Dose Expansion portion&#xD;
             of trial (Stage 2) CrCl &lt; 30 mL/min], Serum amylase or lipase &gt;ULN, International&#xD;
             normalized ratio &gt;1.5 × ULN, or activated partial thromboplastin time &gt;1.5 × ULN&#xD;
&#xD;
          4. Patients with clinically detectable second primary malignant tumors at enrollment or&#xD;
             other malignant tumors within the last 2 years (with the exception of radically&#xD;
             treated basal cell or squamous cell carcinoma of the skin, in situ cervix, or in situ&#xD;
             breast cancer).&#xD;
&#xD;
          5. Any anticancer therapy, including chemotherapy, hormonal therapy, biologic therapy,&#xD;
             vaccine, or radiotherapy within 3 weeks prior to the initiation of study treatment.&#xD;
&#xD;
          6. Herbal therapy within 1 week prior to the initiation of study treatment.&#xD;
&#xD;
          7. Prior use of any anti-cancer vaccine&#xD;
&#xD;
          8. Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib)&#xD;
&#xD;
          9. Prior administration of radioimmunotherapy within 3 months before initiation of study&#xD;
             treatment.&#xD;
&#xD;
         10. Use of strong cytochrome P450 isoform 3A inhibitors and inducers and drugs metabolized&#xD;
             by cytochrome P450 isoform 3A, cytochrome P450 isoform 2B6, and cytochrome P450&#xD;
             isoform 1A2, and are identified as narrow therapeutic drugs within 7 days or 3&#xD;
             half-lives, whichever is longer, prior to initiation of study treatment&#xD;
&#xD;
         11. Adverse events from prior anticancer therapy that have not resolved to Grade ≤1,&#xD;
             except for alopecia.&#xD;
&#xD;
         12. Prior autologous stem cell transplant within 6 months prior to the initiation of study&#xD;
             treatment.&#xD;
&#xD;
         13. Prior allogeneic stem cell transplant within 6 months prior to the initiation of study&#xD;
             treatment or with any evidence of active graft versus host disease or requirement for&#xD;
             immunosuppressants within 28 days prior to the initiation of study treatment.&#xD;
&#xD;
         14. Clinically significant active infection (eg, pneumonia).&#xD;
&#xD;
         15. Major surgical procedure within 4 weeks prior to the initiation of study treatment.&#xD;
&#xD;
         16. Clinically significant history of liver disease, including cirrhosis, current alcohol&#xD;
             abuse, or current known active infection with human immunodeficiency virus, hepatitis&#xD;
             B virus, or hepatitis C virus.&#xD;
&#xD;
         17. Pregnant (positive serum beta human chorionic gonadotropin test) or lactating women.&#xD;
&#xD;
         18. New York Heart Association Class II or greater congestive heart failure.&#xD;
&#xD;
         19. Congenital long QT syndrome or correct QT interval using Fridericia's formula (QTcF)&#xD;
             &gt;480 msec&#xD;
&#xD;
         20. Current use of medication known to cause QT prolongation or Torsades de Pointes&#xD;
&#xD;
         21. History of myocardial infarction or unstable angina within 6 months prior to the&#xD;
             initiation of study treatment.&#xD;
&#xD;
         22. History of stroke or transient ischemic attack within 6 months prior to the initiation&#xD;
             of study treatment.&#xD;
&#xD;
         23. Inability to take oral medication, prior surgical procedures affecting absorption, or&#xD;
             active peptic ulcer disease.&#xD;
&#xD;
         24. Treatment in a clinical study within 30 days prior to the initiation of study&#xD;
             treatment.&#xD;
&#xD;
         25. 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, may&#xD;
             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>Hutchmed</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Vijay Jayaprakash, MD</last_name>
    <phone>9739006617</phone>
    <email>vijayj@hmplglobal.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rathi Pillai, MD</last_name>
    <phone>973-421-5002</phone>
    <email>rathip@hutch-med.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Pacific Cancer Medical Center, Inc.</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Veena Charu</last_name>
    </contact>
    <investigator>
      <last_name>Veena Charu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute</name>
      <address>
        <city>Downey</city>
        <state>California</state>
        <zip>90241</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Richy Agajanian</last_name>
    </contact>
    <investigator>
      <last_name>Richy Agajanian, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Recruiting</status>
    <contact>
      <last_name>Lynn Kong</last_name>
    </contact>
    <investigator>
      <last_name>Lynn Kong, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Summit Medical Group</name>
      <address>
        <city>Florham Park</city>
        <state>New Jersey</state>
        <zip>07932</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Gallinson</last_name>
    </contact>
    <investigator>
      <last_name>David Gallinson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clinical Research Alliance</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Morton Coleman, MD</last_name>
      <phone>516-216-1979</phone>
      <email>mcoleman@researchcra.com</email>
    </contact>
    <investigator>
      <last_name>Morton Colman, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Leo Jenkins Cancer Center/ECU School of Medicine</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Darla Liles</last_name>
    </contact>
    <investigator>
      <last_name>Darla Liles</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Greenville Health System</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>The University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gloria Martinez</last_name>
      <phone>877-632-6789</phone>
      <email>gkmartinez@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Paolo Strati, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Renovatio Clinical</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan Lu</last_name>
    </contact>
    <investigator>
      <last_name>Jonathan Lu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Francesco D Amore</last_name>
    </contact>
    <investigator>
      <last_name>Francesco D Amore</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Helsingin yliopistollinen keskussairaala</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sirpa Leppa, MD</last_name>
      <phone>+358504270820</phone>
      <email>sirpa.leppa@hus.fi</email>
    </contact>
    <investigator>
      <last_name>Sirpa Leppa, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Tampereen yliopistollinen sairaala</name>
      <address>
        <city>Tampere</city>
        <zip>33520</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marjukka Pollari, MD</last_name>
      <phone>+3583311611</phone>
      <email>marjukka.pollari@pshp.fi</email>
    </contact>
    <investigator>
      <last_name>Marjukka Pollari, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Clermont Ferrand - Hôpital d'Estaing</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier Tournilhac</last_name>
    </contact>
    <investigator>
      <last_name>Olivier Tournilhac</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Henri Mondor</name>
      <address>
        <city>Créteil</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Corinne Haioun</last_name>
    </contact>
    <investigator>
      <last_name>Corinne Haioun</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitie-Salpetriere</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sylvain Choquet</last_name>
    </contact>
    <investigator>
      <last_name>Sylvain Choquet</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Poitiers - Hôpital la Milétrie</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephanie Guidez</last_name>
    </contact>
    <investigator>
      <last_name>Stephanie Guidez</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <state>Milano</state>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniela DeLorenzo</last_name>
      <email>delorenzo.daniela@hsr.it</email>
    </contact>
    <investigator>
      <last_name>Andres Ferreri, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)</name>
      <address>
        <city>Bergamo</city>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giuseppe Gritti, MD</last_name>
      <phone>390352673684</phone>
      <email>g.gritti@asst-pg23.it</email>
    </contact>
    <investigator>
      <last_name>Giuseppe Gritti, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carlo Gambacorti-Passerini</last_name>
    </contact>
    <investigator>
      <last_name>Carlo Gambacorti-Passerini</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>KO-MED Centra Kliniczne</name>
      <address>
        <city>Biała Podlaska</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dominika Chwedoruk</last_name>
      <email>dominika.chwedoruk@komed-ck.pl</email>
    </contact>
    <investigator>
      <last_name>Piotr Centkowski, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne</name>
      <address>
        <city>Gdańsk</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michal Taszner</last_name>
      <email>mtaszner@uck.gda.pl</email>
    </contact>
    <investigator>
      <last_name>Michal Taszner, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>BioResearch Group Sp. Z. o. o.</name>
      <address>
        <city>Kajetany</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Nasz Lekarz Przychodnie Medyczne</name>
      <address>
        <city>Toruń</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Judyta Rudzinska</last_name>
      <email>j.rudzinska@naszlekarz.pl</email>
    </contact>
    <investigator>
      <last_name>Dominik Chraniuk</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego</name>
      <address>
        <city>Wrocław</city>
        <zip>50566</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tomasz Wrobel, MD</last_name>
      <phone>48717842754</phone>
      <email>tomasz_wrobel@wp.pl</email>
    </contact>
    <investigator>
      <last_name>Tomasz Wrobel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mafalda Rodrigues</last_name>
      <email>amafaldanrodrigues@vhio.net</email>
    </contact>
    <investigator>
      <last_name>Pau Abrisqueta, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ICO Badalona - Hospital Universitari Germans Trias i Pujol</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laura Abril Sabater</last_name>
    </contact>
    <investigator>
      <last_name>Laura Abril Sabater</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Català d'Oncologia</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Valer Serra</last_name>
    </contact>
    <contact_backup>
      <last_name>avaler@iconcologia.net</last_name>
    </contact_backup>
    <investigator>
      <last_name>Eva Gonzalez Barca, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Javier Lopez Jimenez, MD</last_name>
    </contact>
    <investigator>
      <last_name>Javier Lopez, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adriana Armellini</last_name>
      <email>adriana.armellini@startmadrid.com</email>
    </contact>
    <investigator>
      <last_name>Raul Cordoba, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Infanta Leonor</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jose Angel Hernandez Rivas</last_name>
    </contact>
    <investigator>
      <last_name>Jose Angel Hernandez Rivas</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Quironsalud Madrid</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carmen Martinez Chamorro,</last_name>
    </contact>
    <investigator>
      <last_name>Carmen Martinez Chamorro,</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Centre</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adolfo de la Fuente Burguera</last_name>
    </contact>
    <investigator>
      <last_name>Adolfo de la Fuente Burguera</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luis de la Cruz Merino</last_name>
    </contact>
    <investigator>
      <last_name>Luis de la Cruz Merino</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Seville</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fatima De la Cruz Vicente</last_name>
    </contact>
    <investigator>
      <last_name>Fatima De la Cruz Vicente</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Finland</country>
    <country>France</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>February 22, 2023</last_update_submitted>
  <last_update_submitted_qc>February 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>lymphoma</keyword>
  <keyword>chronic lymphocytic leukemia</keyword>
  <keyword>Hodgkin lymphoma</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/NCT03779113
org study id: 2018-523-00US1
nct id: NCT03779113
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients
      with relapsed or refractory lymphoma who have exhausted approved therapy options. This study
      consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2).
This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients
      with relapsed or refractory lymphoma who have exhausted approved therapy options. This study
      consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2).

      Dose Escalation Stage (Stage 1)

      Dosing will begin at 100 mg once daily (QD). A cycle of study treatment will be defined as 28
      days of continuous dosing. The modified 3+3 design will be applied for dose escalation and
      MTD determination to limit the number of patients exposed to potentially ineffective or
      unsafe doses. The study will enroll 1 patient and the patient will be treated for a 28-day
      cycle in the initial dose cohort. If there is no Dose Limiting Toxicity (DLT) and no more
      than 2 treatment-emergent adverse events (TEAEs) of Common Terminology Criteria for Adverse
      Events (CTCAE) Grade ≥2 in the first treatment cycle, the study will be escalated to the next
      dose cohort and continue with the standard 3+3 design. Otherwise, the trial will revert to a
      standard 3+3 design from the initial dose cohort. A minimum of 3 patients will be enrolled
      and observed for toxicity in each successive dose cohort after the initial dose cohort. If
      the 3 patients initially enrolled in a given dose cohort complete the DLT assessment window
      (Cycle 1, Days 1-28) without experiencing a DLT, 3 patients will be enrolled at the next
      higher dose level. If 2 or more of the initial 3 patients enrolled at any dose level
      experience a DLT during the DLT assessment window, the dose escalation will be halted. If 1
      of the initial 3 patients enrolled at any dose level experiences a DLT during the DLT
      assessment window, additional patients will be enrolled at that dose level for a minimum of 6
      evaluable patients for DLT. If a DLT is observed in 1 of the 6 valuable patients at this dose
      level, dose escalation will proceed to the next pre- defined dose level. If DLTs are observed
      in 2 or more of the 6 evaluable patients at a given dose level, the dose escalation will be
      halted. If the dose escalation is completed due to 2 or more DLTs at a dose level and that
      dose level is ≥50% higher than the previous dose level, then an intermediate dose level may
      be evaluated for toxicity in the same manner as described above. If the dose level is <50%
      higher than the previous dose level, in which only 3 DLT evaluable patients were enrolled, 3
      additional patients will be enrolled at that dose level to comprise 6 DLT evaluable patients.

      The proposed dose escalation scheme comprises Cohorts 1 to 5 with dosing levels of 100 mg QD,
      200 mg QD, 400 mg QD, 600 mg QD and 800 mg QD, respectively. The need for dose escalation
      beyond 800 mg QD, the specific dose to be tested and the potential for twice-daily (BID)
      dosing will be evaluated jointly by investigators and the sponsor based on the cumulative
      clinical safety, pharmacokinetic, and preliminary efficacy data. Safety monitoring and
      evaluation of dose escalation will be carried out by the Safety Review Committee, which will
      be comprised of the sponsor's study team members (including medical monitor, safety monitor
      and and Pharmacokinetic scientist) and the site principal investigators. The adverse event
      profile and serum concentration of HMPL-523 data will be evaluated to determine whether it is
      safe to continue the assigned HMPL-523 dose for dose escalation or whether the dose should be
      de-escalated to the lower dose level.

      Dose Expansion Stage (Stage 2)

      The adverse event profile, serum concentration, and preliminary anti-tumor activity of
      HMPL-523 at the maximum tolerated dose(MTD)/recommended phase 2 dose(RP2D) will be further
      evaluated in approximately 50 patients with relapsed or refractory indolent B-cell
      non-Hodgkin's lymphomas. The tumor types of the dose expansion stage are restricted to:

        -  10 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

        -  20 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma post-BTK
           exposure

        -  10 patients with mantle cell lymphoma

        -  20 patients with follicular lymphoma (Grade 1-3a)

        -  10 patients with marginal zone lymphoma

        -  10 patients with waldenström's macroglobulinemia/lymphoplasmacytic lymphoma

        -  10 patients with peripheral T- cell lymphoma

        -  10 patients with cutaneous B-cell lymphoma

        -  10 patients with hodgkin lymphoma

      Patients will receive HMPL-523 at the MTD/RP2D for continuous 28-day treatment cycles until
      disease progression, death, intolerable toxicity, at investigator's discretion that the
      patient can no longer benefit from the study treatment, patient withdrawal from the study, or
      the end of study, whichever comes first.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
time frame: From first dose to within 30 days after the last dose
description: The safety and tolerability of HMPL-523 will be evaluated based on adverse events data.
measure: Maximum plasma concentration (Cmax)
time frame: From Cycle 1, Day 1, 5 min pre-dose 1st dose until Cycle 1, Day 28 8 hours post-dose.
description: To Characterize the pharmacokinetic properties of HMPL-523 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, 5 min pre-dose 1st dose until Cycle 1, Day 28 8 hours post-dose.
description: To characterize the pharmacokinetic properties of HMPL-523 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 after the last dose
description: To evaluate the anti-tumor activity of HMPL-523 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 to received study drug (HMPL-523)
intervention type: Drug
intervention name: HMPL-523
description: Oral HMPL-523
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: Hutchmed
last name: Vijay Jayaprakash, MD
phone: 9739006617
email: vijayj@hmplglobal.com
last name: Rathi Pillai, MD
phone: 973-421-5002
email: rathip@hutch-med.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Denmark
country: Finland
country: France
country: Italy
country: Poland
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
sharing ipd: No