<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/NCT01705847</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-315-0102</org_study_id>
    <secondary_id>2012-000360-19</secondary_id>
    <nct_id>NCT01705847</nct_id>
  </id_info>
  <brief_title>A Phase 1b Study Evaluating GS-9820 in Subjects With Lymphoid Malignancies</brief_title>
  <official_title>A Phase 1b Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GS-9820 in Subjects With Lymphoid Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to determine the appropriate dosing regimen of GS-9820 in subjects with&#xD;
      lymphoid malignancies. This is a Phase 1b, open-label, dose-escalation and expansion study&#xD;
      evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of GS-9820.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</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>Maximum tolerated dose (MTD)</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>MTD will be assessed to determine the appropriate dosing regimens for use in future clinical trials of GS-9820 in subjects with lymphoid malignancies.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall safety</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Overall safety will be assessed by overall safety profile, enumeration and description of any dose-limiting toxicities, serious adverse events, or adverse events leading to discontinuation of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of GS-9820 as measured by Cmax, Tmax, Ctrough, and AUC</measure>
    <time_frame>Baseline to Day 29</time_frame>
    <description>Cmax is defined as the maximum concentration of drug&#xD;
Tmax is defined as the time of Cmax&#xD;
Ctrough is defined as the trough concentration&#xD;
AUC is defined as the area under the plasma concentration versus time curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics to measure changes in the phosphatidylinositol 3-kinase (P13K) delta pathway activation and changes in plasma concentration of disease-associated chemokines and cytokines</measure>
    <time_frame>Baseline to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor control</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Tumor control as assessed by overall response rate (ORR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), percent change in lymph node area, lymph node response rate, splenomegaly response rate, ALC response rate, hepatomegaly response rate, platelet response rate, hemoglobin response rate, and neutrophil response rate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient well-being assessed using changes in baseline in HRQL (health related quality of life questionnaire) domain and symptom scores based on the Functional Assessment of Cancer Therapy: Lymphoma (FACT-Lym)</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug exposure</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Drug administration for GS-9820 as assessed by prescribing records and GS-9820 compliance as assessed by quantification of used and unused drug.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Lymphoid Malignancies</condition>
  <arm_group>
    <arm_group_label>GS-9820</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be sequentially enrolled at progressively higher dose levels to receive GS-9820 administered twice a day. Escalation will proceed to the maximum tolerated dose (MTD), defined as the highest tested dose associated with a rate of dose-limiting toxicities (DLT) of &lt; 33% during the first 4 weeks of therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GS-9820</intervention_name>
    <description>GS-9820 tablets containing 200 mg of GS-9820 administered orally</description>
    <arm_group_label>GS-9820</arm_group_label>
    <other_name>CAL-120</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Previously treated recurrent B-cell iNHL, DLBCL, MCL, HL or CLL&#xD;
&#xD;
          -  Measurable lymphadenopathy&#xD;
&#xD;
          -  Requires therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recent history of a major non-lymphoid malignancy&#xD;
&#xD;
          -  Evidence of ongoing infection&#xD;
&#xD;
          -  Concurrent participation in another therapeutic clinical trial&#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>Henry Adewoye, MD</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VU Medical Center (VUmc)</name>
      <address>
        <city>Amsterdam</city>
        <zip>1081 HV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Antonius Hospital</name>
      <address>
        <city>Nieuwegein</city>
        <zip>3435 CM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus MC - Daniel den Hoed Cancer Center</name>
      <address>
        <city>Rotterdam</city>
        <zip>3075 EA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <last_update_submitted>May 16, 2016</last_update_submitted>
  <last_update_submitted_qc>May 16, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 17, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic lymphocytic leukemia (CLL)</keyword>
  <keyword>non-Hodgkin lymphoma (NHL)</keyword>
  <keyword>Hodgkin lymphoma (HL)</keyword>
  <keyword>indolent non-Hodgkin lymphoma (iNHL)</keyword>
  <keyword>diffuse large B-cell lymphoma-activated B-cell (DLBCL-ABC)</keyword>
  <keyword>DLBCL-germinal center B-cell (GCB)</keyword>
  <keyword>mantle cell lymphoma (MCL)</keyword>
  <keyword>GS-9820</keyword>
  <keyword>phosphatidylinositol 3-kinase (PI3K)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT01705847
org study id: GS-US-315-0102
secondary id: 2012-000360-19
nct id: NCT01705847
lead sponsor: 
has dmc: No
This study is to determine the appropriate dosing regimen of GS-9820 in subjects with
      lymphoid malignancies. This is a Phase 1b, open-label, dose-escalation and expansion study
      evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of GS-9820.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD)
time frame: Up to 4 weeks
description: MTD will be assessed to determine the appropriate dosing regimens for use in future clinical trials of GS-9820 in subjects with lymphoid malignancies.
measure: Overall safety
time frame: Up to 5 years
description: Overall safety will be assessed by overall safety profile, enumeration and description of any dose-limiting toxicities, serious adverse events, or adverse events leading to discontinuation of study drug.
measure: Pharmacokinetic parameters of GS-9820 as measured by Cmax, Tmax, Ctrough, and AUC
time frame: Baseline to Day 29
description: Cmax is defined as the maximum concentration of drug
Tmax is defined as the time of Cmax
Ctrough is defined as the trough concentration
AUC is defined as the area under the plasma concentration versus time curve
measure: Pharmacodynamics to measure changes in the phosphatidylinositol 3-kinase (P13K) delta pathway activation and changes in plasma concentration of disease-associated chemokines and cytokines
time frame: Baseline to Day 29
measure: Tumor control
time frame: Up to 5 years
description: Tumor control as assessed by overall response rate (ORR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), percent change in lymph node area, lymph node response rate, splenomegaly response rate, ALC response rate, hepatomegaly response rate, platelet response rate, hemoglobin response rate, and neutrophil response rate.
measure: Patient well-being assessed using changes in baseline in HRQL (health related quality of life questionnaire) domain and symptom scores based on the Functional Assessment of Cancer Therapy: Lymphoma (FACT-Lym)
time frame: Up to 5 years
measure: Drug exposure
time frame: Up to 5 years
description: Drug administration for GS-9820 as assessed by prescribing records and GS-9820 compliance as assessed by quantification of used and unused drug.
arm group label: GS-9820
arm group type: Experimental
description: Participants will be sequentially enrolled at progressively higher dose levels to receive GS-9820 administered twice a day. Escalation will proceed to the maximum tolerated dose (MTD), defined as the highest tested dose associated with a rate of dose-limiting toxicities (DLT) of < 33% during the first 4 weeks of therapy.
intervention type: Drug
intervention name: GS-9820
description: GS-9820 tablets containing 200 mg of GS-9820 administered orally
arm group label: GS-9820
other name: CAL-120
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Henry Adewoye, MD
role: Study Director
affiliation: Gilead Sciences
facility: 
facility: 
facility: 
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Neoplasms