<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/NCT03797456</url>
  </required_header>
  <id_info>
    <org_study_id>ICP-CL-00104</org_study_id>
    <nct_id>NCT03797456</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate ICP-022 in Patients With R/R Marginal Zone Lymphoma (MZL)</brief_title>
  <official_title>A Multicenter, Open-label Study to Evaluate the Safety and Efficacy of ICP-022 in Patients With Relapsed/Refractory Marginal Zone Lymphoma (MZL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing InnoCare Pharma Tech Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing InnoCare Pharma Tech Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The phase II clinical study is to investigate the safety, tolerability, efficacy and&#xD;
      pharmacokinetics of ICP-022.&#xD;
&#xD;
      Safety, tolerability evaluation, and anti-tumor effects of ICP-022 in Chinese patients with&#xD;
      R/R MZL will be evaluated in approximately 110 subjects. Pharmacokinetics of ICP-022 will be&#xD;
      evaluated in approximately 20 subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The efficacy measured by overall response rate (ORR) in Part II according to the 2014 International Working Group NHL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The safety of ICP-022 measured by the occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progressioin free survival (PFS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Progression free survival (PFS) is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DR)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Duration of response as defined as the period from the first response (at least PR) to treatment until evidence of disease progression, relapse or death of any cause. Patients alive without progression and relapse will be censored at the latest tumor assessment date or the stopping date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Overall survival is defined as the period from the induction registration to death from any cause. Patients who have not died until the time of the analysis will be censored at their last contact date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration time curve up to the time &quot;t&quot; (AUC(0-t))</measure>
    <time_frame>up to 4 weeks</time_frame>
    <description>Area under the concentration time curve up to the time &quot;t&quot; (AUC(0-t)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma drug concentrations (Cmax)</measure>
    <time_frame>up to 4 weeks</time_frame>
    <description>Individual plasma concentrations of ICP-022 will be measured and Cmax will be calculated with noncompartmental analysis using WinNonlin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum plasma drug concentrations (Tmax)</measure>
    <time_frame>up to 4 weeks</time_frame>
    <description>Time of maximum plasma drug concentrations (Tmax) of ICP-022 will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent half-life for designated elimination phases (t½)</measure>
    <time_frame>up to 4 weeks</time_frame>
    <description>Apparent half-life for designated elimination phases (t½) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration time curve up to the last data point above LOQ (AUC(last))</measure>
    <time_frame>up to 4 weeks</time_frame>
    <description>Area under the concentration time curve up to the last data point above LOQ (AUC(last)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">111</enrollment>
  <condition>MZL</condition>
  <arm_group>
    <arm_group_label>ICP-022</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ICP-022</intervention_name>
    <description>ICP-022 (tablets, 50 mg) is given orally at the dose of 150 mg/day from day 1 to day 28 of each cycle for up to a total of 6 cycles or until progression.</description>
    <arm_group_label>ICP-022</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women between 18 and 75 years old&#xD;
&#xD;
          -  Histologically confirmed marginal zone lymphoma (MZL), and at least one measurable&#xD;
             tumor of greater than 1.5 centimeter outside of the spleen&#xD;
&#xD;
          -  Subjects with refractory or relapsed MZL who has received at least 1 but no more than&#xD;
             4 prior therapies for MZL&#xD;
&#xD;
          -  ECOG performance status of 0-2&#xD;
&#xD;
          -  Documented failure to achieve at least partial response (PR) or documented disease&#xD;
             progression after response to the most recent treatment regimen&#xD;
&#xD;
          -  Subjects who have indications for treatment (threatened end-organ function, bulky&#xD;
             disease &gt;5cm, symptoms, steady progression, wish to treat)&#xD;
&#xD;
          -  Subjects meet the following laboratory parameters:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥ 1.5×109/L Platelet count ≥ 75×109/L,&#xD;
                  independent of growth factor support within 7 days of the first dose with study&#xD;
                  drug, Hemoglobin ≥ 75 g/L; ANC ≥ 1.0×109/L, Platelet count ≥ 50×109/L, Hemoglobin&#xD;
                  ≥ 50 g/L; if bone marrow involvement&#xD;
&#xD;
               2. Total bilirubin ≤ 1.5× ULN; AST or ALT ≤ 2× ULN; Creatinine ≤ 1.5× ULN; Amylase ≤&#xD;
                  ULN and Lipase ≤ ULN&#xD;
&#xD;
               3. International normalized ratio (INR) ≤ 1.5 ULN&#xD;
&#xD;
          -  Life expectancy ≥ 3 months&#xD;
&#xD;
          -  Able to provide signed written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of other active malignancies within 5 years of study entry, unless cured&#xD;
             without evidence of relapse or metastasis&#xD;
&#xD;
          -  Current or history of lymphoma involved central nervous system&#xD;
&#xD;
          -  Prior corticosteroids (at dosages equivalent to prednisone &gt; 20 mg/day) given with&#xD;
             anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, radiation&#xD;
             therapy, or antibody-based therapies or anti-cancer TCM within 4 weeks of the start of&#xD;
             study drug&#xD;
&#xD;
          -  Non-hematological toxicity must recover to ≤ Grade 1 from prior anti-cancer therapy&#xD;
             (except for alopecia)&#xD;
&#xD;
          -  Current clinically significant cardiovascular disease including:&#xD;
&#xD;
               -  Any class 3 or 4 cardiac disease such as arrhythmia, congestive heart failure or&#xD;
                  myocardial infarction defined by the New York Heart Association Functional&#xD;
                  Classification, or left ventricular ejection fraction (LVEF) &lt; 50%&#xD;
&#xD;
               -  Primary cardiomyopathy&#xD;
&#xD;
               -  Clinical significant QTc prolong history or QTc&gt;470ms (female) QTc&gt;450ms (male)&#xD;
&#xD;
               -  Uncontrolled hypertension&#xD;
&#xD;
          -  Known active bleeding within 2 months of screening or currently taking&#xD;
             anticoagulant/antiplatelet drugs&#xD;
&#xD;
          -  Urine protein ≥ 2+ and quantitation ≥ 2g/24hours&#xD;
&#xD;
          -  History of deep vein thrombosis or pulmonary embolism&#xD;
&#xD;
          -  Toxicity must be recovered to ≤ Grade 1 from prior anti-cancer therapy&#xD;
&#xD;
          -  Disease significantly affecting gastrointestinal function such as dysphagia, chronic&#xD;
             diarrhea, intestinal obstruction, or resection of the stomach&#xD;
&#xD;
          -  Prior organ or hematopoietic stem cell transplant&#xD;
&#xD;
          -  Major surgery within 6 weeks of screening, except for diagnostic test or vascular&#xD;
             access setup&#xD;
&#xD;
          -  Known active infection with HBV, HCV or HIV or any uncontrolled active systemic&#xD;
             infection&#xD;
&#xD;
          -  Any history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation&#xD;
             pneumonitis, drug-related pneumonia, severe lung function impairment&#xD;
&#xD;
          -  Prior exposure to a BTK or BCR pathway inhibitor (PI3K or Syk) and BCL-2 inhibitor&#xD;
&#xD;
          -  Suitable and ready for allogeneic stem cell transplant&#xD;
&#xD;
          -  Inability to comply with study procedures&#xD;
&#xD;
          -  Drug abuser or alcoholics&#xD;
&#xD;
          -  Lactating or pregnant women, or women who will not use contraception during the study&#xD;
             and for 180 days after the last dose of study drug if sexually active and able to bear&#xD;
             children&#xD;
&#xD;
          -  Requires treatment with moderate or strong cytochrome P450 family 3, subfamily A&#xD;
             (CYP3A) inhibitors or strong CYP3A inducers.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jun Zhu, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>102206</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>October 10, 2022</last_update_submitted>
  <last_update_submitted_qc>October 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 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>Lymphoma, B-Cell, Marginal Zone</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/NCT03797456
org study id: ICP-CL-00104
nct id: NCT03797456
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The phase II clinical study is to investigate the safety, tolerability, efficacy and
      pharmacokinetics of ICP-022.

      Safety, tolerability evaluation, and anti-tumor effects of ICP-022 in Chinese patients with
      R/R MZL will be evaluated in approximately 110 subjects. Pharmacokinetics of ICP-022 will be
      evaluated in approximately 20 subjects.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR)
time frame: Up to 3 years
description: The efficacy measured by overall response rate (ORR) in Part II according to the 2014 International Working Group NHL
measure: Occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I
time frame: Up to 3 years
description: The safety of ICP-022 measured by the occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I
measure: Progressioin free survival (PFS)
time frame: Up to 3 years
description: Progression free survival (PFS) is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.
measure: Duration of Response (DR)
time frame: Up to 3 years
description: Duration of response as defined as the period from the first response (at least PR) to treatment until evidence of disease progression, relapse or death of any cause. Patients alive without progression and relapse will be censored at the latest tumor assessment date or the stopping date.
measure: Overall survival (OS)
time frame: Up to 3 years
description: Overall survival is defined as the period from the induction registration to death from any cause. Patients who have not died until the time of the analysis will be censored at their last contact date.
measure: Area under the concentration time curve up to the time "t" (AUC(0-t))
time frame: up to 4 weeks
description: Area under the concentration time curve up to the time "t" (AUC(0-t)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.
measure: Maximum plasma drug concentrations (Cmax)
time frame: up to 4 weeks
description: Individual plasma concentrations of ICP-022 will be measured and Cmax will be calculated with noncompartmental analysis using WinNonlin.
measure: Time of maximum plasma drug concentrations (Tmax)
time frame: up to 4 weeks
description: Time of maximum plasma drug concentrations (Tmax) of ICP-022 will be recorded.
measure: Apparent half-life for designated elimination phases (t½)
time frame: up to 4 weeks
description: Apparent half-life for designated elimination phases (t½) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.
measure: Area under the concentration time curve up to the last data point above LOQ (AUC(last))
time frame: up to 4 weeks
description: Area under the concentration time curve up to the last data point above LOQ (AUC(last)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.
arm group label: ICP-022
arm group type: Experimental
intervention type: Drug
intervention name: ICP-022
description: ICP-022 (tablets, 50 mg) is given orally at the dose of 150 mg/day from day 1 to day 28 of each cycle for up to a total of 6 cycles or until progression.
arm group label: ICP-022
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jun Zhu, PhD
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
facility: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma, B-Cell, Marginal Zone
sharing ipd: No