<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/NCT02258555</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-325-1348</org_study_id>
    <secondary_id>2014-005441-53</secondary_id>
    <nct_id>NCT02258555</nct_id>
  </id_info>
  <brief_title>Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of GS-9901 in Adults With Relapsed or Refractory Follicular Lymphoma, Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, or Small Lymphocytic Lymphoma</brief_title>
  <official_title>A Phase 1b Dose-escalation Study Evaluating the Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of GS-9901 in Subjects With Relapsed or Refractory Follicular Lymphoma, Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, or Small Lymphocytic Lymphoma</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 will evaluate the safety and tolerability of GS-9901 monotherapy in adults with&#xD;
      follicular lymphoma (FL), marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL),&#xD;
      or small lymphocytic lymphoma (SLL). The study will also characterize the pharmacokinetic&#xD;
      (PK) profile of GS-9901, determine the appropriate dosing regimen of GS-9901 for use in&#xD;
      future clinical trials, and to evaluate the efficacy of GS-9901 monotherapy in adults with&#xD;
      FL, MZL, CLL, or SLL.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</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>Occurrence of adverse events (AEs) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Overall safety profile will be characterized by number of participants experiencing adverse events or laboratory abnormalities.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurrence of AEs and clinical laboratory abnormalities not defined as DLTs</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall safety profile will be characterized by number of participants experiencing adverse events or laboratory abnormalities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Progression-free survival (PFS) is defined as the interval from the start of study therapy to the earlier of the first documentation of definitive disease progression or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Duration of response (DOR) is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK profile of GS-9901</measure>
    <time_frame>Predose and 0.5, 1, 1.5, 2, 3, 4, 6, and 24 hours postdose on Days 1 and 15; predose and 1.5 hours postdose on Days 29, 43, 85, and 169</time_frame>
    <description>This endpoint will measure the plasma PK profile of GS-9901. The following parameters will be measured:&#xD;
Cmax: maximum observed concentration of drug in plasma&#xD;
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Follicular Lymphoma</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <condition>Marginal Zone Lymphoma</condition>
  <arm_group>
    <arm_group_label>GS-9901</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive one of 6 escalating doses of GS-9901 once daily until unacceptable toxicity, substantial noncompliance, disease progression, pregnancy, initiation of another anti-cancer or experimental therapy, or other protocol-specified reasons for GS-9901 discontinuation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GS-9901</intervention_name>
    <description>GS-9901 tablets administered orally</description>
    <arm_group_label>GS-9901</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of FL, MZL, SLL, or CLL (meeting International Workshop on CLL [IWCLL]&#xD;
             Criteria, 2008) as documented by medical records and with histology based on criteria&#xD;
             established by the World Health Organization&#xD;
&#xD;
               -  FL Grades 1, 2, or 3a&#xD;
&#xD;
               -  SLL with absolute lymphocyte count of &lt; 5 x 10^9/L at initial diagnosis&#xD;
&#xD;
               -  MZL (splenic, nodal, or extra-nodal)&#xD;
&#xD;
          -  Prior treatment for FL or CLL/SLL with ≥ 1 prior chemotherapy-based or&#xD;
             immunotherapy-based regimen with no approved therapies available&#xD;
&#xD;
          -  Presence of radiographically measurable lymphadenopathy or extra nodal lymphoid&#xD;
             malignancy&#xD;
&#xD;
          -  All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before the&#xD;
             start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted], or&#xD;
             bone marrow parameters [any of Grade 1, 2, or 3 permitted)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) ≤ 2&#xD;
&#xD;
          -  Able to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of lymphoid malignancy other than FL, MZL, SLL, or CLL&#xD;
&#xD;
          -  History of myelodysplastic syndrome&#xD;
&#xD;
          -  History of a non-lymphoid malignancy except for the following: adequately treated&#xD;
             local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ,&#xD;
             superficial bladder cancer, asymptomatic prostate cancer without known metastatic&#xD;
             disease and with no requirement for therapy or requiring only hormonal therapy and&#xD;
             with normal prostate-specific antigen for ≥ 1 year prior to start of study therapy, or&#xD;
             any other cancer that has been in complete remission for ≥ 5 years&#xD;
&#xD;
          -  Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of&#xD;
             start of study therapy&#xD;
&#xD;
          -  Ongoing drug-induced pneumonitis&#xD;
&#xD;
          -  Ongoing inflammatory bowel disease&#xD;
&#xD;
          -  History of prior allogeneic bone marrow progenitor cell or solid organ transplantation&#xD;
&#xD;
          -  History of prior therapy with any inhibitor of serine/threonine kinase (AKT), Bruton&#xD;
             tyrosine kinase (BTK), Janus kinase (JAK), mammalian target of rapamycin (mTOR),&#xD;
             phosphatidylinositol 3-kinase (PI3K), or spleen tyrosine kinase (SYK)&#xD;
&#xD;
          -  Ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of&#xD;
             lymphoid malignancy&#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>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Center of Fresno</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center Central Connecticut</name>
      <address>
        <city>Southington</city>
        <state>Connecticut</state>
        <zip>06489</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lombardi Cancer Center-Georgetown University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>02007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Medical Specialties</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>October 15, 2015</last_update_submitted>
  <last_update_submitted_qc>October 15, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 19, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic lymphocytic leukemia (CLL)</keyword>
  <keyword>Follicular lymphoma (FL)</keyword>
  <keyword>Small Lymphocytic Lymphoma (SLL)</keyword>
  <keyword>Phosphatidylinositol 3 kinase (PI3K)</keyword>
  <keyword>Marginal Zone Lymphoma (MZL)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</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/NCT02258555
org study id: GS-US-325-1348
secondary id: 2014-005441-53
nct id: NCT02258555
lead sponsor: 
has dmc: No
This study will evaluate the safety and tolerability of GS-9901 monotherapy in adults with
      follicular lymphoma (FL), marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL),
      or small lymphocytic lymphoma (SLL). The study will also characterize the pharmacokinetic
      (PK) profile of GS-9901, determine the appropriate dosing regimen of GS-9901 for use in
      future clinical trials, and to evaluate the efficacy of GS-9901 monotherapy in adults with
      FL, MZL, CLL, or SLL.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of adverse events (AEs) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs)
time frame: Up to 28 days
description: Overall safety profile will be characterized by number of participants experiencing adverse events or laboratory abnormalities.
measure: Occurrence of AEs and clinical laboratory abnormalities not defined as DLTs
time frame: Up to 2 years
description: Overall safety profile will be characterized by number of participants experiencing adverse events or laboratory abnormalities.
measure: Overall response rate
time frame: Up to 2 years
description: Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).
measure: Progression-free survival
time frame: Up to 2 years
description: Progression-free survival (PFS) is defined as the interval from the start of study therapy to the earlier of the first documentation of definitive disease progression or death from any cause.
measure: Duration of response
time frame: Up to 2 years
description: Duration of response (DOR) is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause.
measure: PK profile of GS-9901
time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, and 24 hours postdose on Days 1 and 15; predose and 1.5 hours postdose on Days 29, 43, 85, and 169
description: This endpoint will measure the plasma PK profile of GS-9901. The following parameters will be measured:
Cmax: maximum observed concentration of drug in plasma
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
arm group label: GS-9901
arm group type: Experimental
description: Participants will receive one of 6 escalating doses of GS-9901 once daily until unacceptable toxicity, substantial noncompliance, disease progression, pregnancy, initiation of another anti-cancer or experimental therapy, or other protocol-specified reasons for GS-9901 discontinuation.
intervention type: Drug
intervention name: GS-9901
description: GS-9901 tablets administered orally
arm group label: GS-9901
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: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Lymphoma, Follicular
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, B-Cell, Marginal Zone