<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/NCT04431089</url>
  </required_header>
  <id_info>
    <org_study_id>SHC014-II-01</org_study_id>
    <nct_id>NCT04431089</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of SHC014748M in Patients With Relapsed or Refractory Follicular (FL) or Marginal Zone (MZL) Lymphoma</brief_title>
  <official_title>A Phase II Multicenter Study to Investigate the Efficacy and Safety of SHC014748M in Patients With Relapsed or Refractory Follicular (FL) or Marginal Zone (MZL) Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanjing Sanhome Pharmaceutical, Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanjing Sanhome Pharmaceutical, 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 purpose of this study is to evaluate the efficacy and safety of SHC014748M in patients&#xD;
      with relapsed or refractory relapsed or refractory follicular (FL) or marginal one (MZL)&#xD;
      lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase II, multicenter study to assess the efficacy and safety of SHC014748M, an&#xD;
      oral inhibitor of PI3K delta, in patients with relapsed or refractory relapsed or refractory&#xD;
      follicular (FL) or marginal one (MZL) lymphoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 9, 2020</start_date>
  <completion_date type="Anticipated">July 2021</completion_date>
  <primary_completion_date type="Anticipated">April 2021</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>Objective Response Rate (ORR)</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Proportion of patients who have either a complete or partial response before any treatment change.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lymph Node Response (LNR)</measure>
    <time_frame>up to 12 months</time_frame>
    <description>LNR was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the product of the perpendicular diameters (SPD) of measurable index lesions.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Response (TTR)</measure>
    <time_frame>up to 12 months</time_frame>
    <description>TTR was defined as the interval from the start of SHC014748M treatment to the first documentation of complete response(CR) or partial response(PR).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>up to 12 months</time_frame>
    <description>PFS was defined as the interval from the start of SHC014748M treatment to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using Kaplan-Meier (KM) estimates.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>up to 12 months</time_frame>
    <description>DOR was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression as or death from any cause. DOR was analyzed using KM estimates.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Scale.</measure>
    <time_frame>up to 12 months</time_frame>
    <description>The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on health related quality of life(HRQL) and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess non-Hodgkins lymphoma(NHL) related symptoms and concerns. All questions are answered on a 5-point scale ranging from &quot;not at all&quot; (0) to &quot;very much&quot; (4). Higher scores are associated with a better quality of life.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of SHC014748M Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms.</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Parameter: Cmax</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Parameter: Tmax</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Parameter: ACUlast</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">122</enrollment>
  <condition>Follicular Lymphoma(FL)</condition>
  <condition>Marginal Zone Lymphoma(MZL)</condition>
  <arm_group>
    <arm_group_label>SHC014748M treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHC014748M capsule, 200mg QD, 28 days for each cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHC014748M</intervention_name>
    <description>Each treatment cycle is comprised of 28-day consecutive dosing of SHC014748M, 200mg QD (Days 1 to28). Upon completion of each cycle, patients may continue to receive oral SHC014748M if they can benefit from the treatment and the toxicity is tolerable.</description>
    <arm_group_label>SHC014748M treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult, male and female volunteers, above 18 years of age inclusive.&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of relapsed or refractory FL(grade&#xD;
             1, 2 or 3a) and MZL, including splenic marginal zone lymphoma(SMZL), nodal marginal&#xD;
             zone B cell lymphoma(NMZL) and mucosa associated lymphoid tissue(MALT) lymphoma.&#xD;
             Relapse refers to disease progression after adequate treatment to remission；refractory&#xD;
             refers to no remission after adequate treatment. The above &quot;remission&quot; includes&#xD;
             complete remission and partial remission. Adequate treatment refers to two or more&#xD;
             treatments with CD20 monoclonal antibody (CDE approved for marketing) combined with&#xD;
             alkylation agent, including but not limited to bendamustine, cyclophosphamide,&#xD;
             ifosfamide, chlorambucil, melphalan, busulfan and nitrosoureas.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.&#xD;
&#xD;
          -  Life expectancy ≥ 3 months.&#xD;
&#xD;
          -  Patients have at least 1 measurable lesion that measures ≥1.5 cm in a single dimension&#xD;
             as assessed by CT or MRI.&#xD;
&#xD;
          -  Adequate organ function, as defined by the following values:ANC≥1.0×10^9/L；&#xD;
             PLT≥50×10^9/L;Hb≥80 g/L;TBIL≤2×ULN(TBIL&gt;2×ULN for subjects with Gilbert&#xD;
             syndrome,TBIL&gt;3×ULN for subjects with focal compression of bile duct judged by&#xD;
             investigators); ALT and AST≤2.5×ULN(ALT and AST≤5×ULN for subjects with impaired liver&#xD;
             function caused by hepatic infiltration);blood urea nitrogen(BUN) and&#xD;
             Cr≤1.5×ULN;LVEF≥50%;QTcF &lt;450 ms for male, QTcF &lt;470 ms for female.&#xD;
&#xD;
          -  Men and women of childbearing potential are willing to employ an effective method of&#xD;
             contraception for the entire duration of study and 6 months after the last dose, and&#xD;
             female subjects of childbearing potential have a negative pregnancy test at baseline.&#xD;
&#xD;
          -  Subjects did not participate in other clinical trials within 1 month prior to study&#xD;
             entry.&#xD;
&#xD;
          -  Provision of signed and dated, written informed consent prior to any study-specific&#xD;
             evaluation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with any PI3Kδ inhibitors.&#xD;
&#xD;
          -  Evidence of aggressive lymphoma(suspected clinical transformation should be conformed&#xD;
             by biopsy).&#xD;
&#xD;
          -  Had any other anti-tumor treatment within 4 weeks prior to screening(including&#xD;
             radiotherapy, chemotherapy, Chinese herbal anti-tumor treatment and major surgery);&#xD;
             targeted therapy with 5 half-life period prior to screening.&#xD;
&#xD;
          -  Evidence of central nervous system involvement of the malignancy.&#xD;
&#xD;
          -  Evidence of severe or uncontrolled systemic diseases, including uncontrolled&#xD;
             hypertension, active bleeding diatheses, uncontrolled pleural effusion and ascites,&#xD;
             uncontrolled diabetes, severe or debilitating lung disease.&#xD;
&#xD;
          -  Any of the severe heart diseases, including New York Heart Association (NYHA) Class II&#xD;
             or greater heart failure, arrhythmias requiring medical treatment, and history of&#xD;
             myocardial infarction or unstable angina within 6 months prior to screening.Requiring&#xD;
             any concomitant medication known to prolong the QT interval within 5 half-life period.&#xD;
&#xD;
          -  Evidence of active bacterial, fungal, or viral infection, and need systemic treatment.&#xD;
&#xD;
          -  Active infection with hepatitis B virus (HBV) (HBsAg positive, or HBsAg negative and&#xD;
             HBV-DNA positive), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).&#xD;
&#xD;
          -  Concomitant use of any strong inhibitors or inducers of CYP3A4(except drug withdrawal&#xD;
             prior to first dose of investigational drug.&#xD;
&#xD;
          -  Use of granulocyte colony-stimulating factor(G-CSF) or blood transfusion within 7 days&#xD;
             before the hematology test at screening.&#xD;
&#xD;
          -  Prior autologous hematopoietic stem cell transplantation within 3 months prior to&#xD;
             screening.&#xD;
&#xD;
          -  History of immune deficiency(acquired and congenital), or history of organ&#xD;
             transplantation, or allogeneic bone marrow or hematopoietic stem cell transplantation;&#xD;
             with active autoimmune disease or history of autoimmune disease including Interstitial&#xD;
             pneumonia, autoimmune enteritis, autoimmune hepatitis and systemic lupus erythematosus&#xD;
&#xD;
          -  History of any uncured malignant tumor in the past five years except for the&#xD;
             following: clinically cured cervical or breast carcinoma in situ, local basal cell or&#xD;
             squamous cell carcinoma of the skin, thyroid tumor.&#xD;
&#xD;
          -  Inability to swallow the drug, or history of diseases affecting gastrointestinal&#xD;
             functions significantly including malabsorption syndrome,bariatric&#xD;
             surgery,inflammatory bowel disease, partial or complete intestinal obstruction.&#xD;
&#xD;
          -  Adverse events occurred during previous anticancer therapy have not been recovered to&#xD;
             ≤1(CTCAE 5.0).&#xD;
&#xD;
          -  History of hypersensitivity to the main composition or any inactive excipient of the&#xD;
             study drug.&#xD;
&#xD;
          -  Women who are breastfeeding.&#xD;
&#xD;
          -  With alcohol or drug abuse disorder.&#xD;
&#xD;
          -  History of stroke or intracranial hemorrhage with 6 months prior to screening.&#xD;
&#xD;
          -  Attenuated live vaccination within 4 weeks prior to screening.&#xD;
&#xD;
          -  With basic medical condition leading to risk of taking study drugs judged by&#xD;
             investigators, or with confusion to toxicity and adverse events.&#xD;
&#xD;
          -  Judgment by the investigator that the patient should not participate in the study.&#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>Jianyong Li, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affiliated Hospital with Nanjing Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chao Wang</last_name>
    <phone>13851803148</phone>
    <email>wangchao@sanhome.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hongchan Zhang</last_name>
    <phone>15150516871</phone>
    <email>zhanghcyf@sanhome.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The First Affiliated Hospital with Nanjing Medical University</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jianyong Li, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital, Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jie Jin, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>January 27, 2021</last_update_submitted>
  <last_update_submitted_qc>January 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>FL</keyword>
  <keyword>MZL</keyword>
  <keyword>SHC014748M</keyword>
  <keyword>Phosphatidylinositol 3-kinase (PI3K)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <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/NCT04431089
org study id: SHC014-II-01
nct id: NCT04431089
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of SHC014748M in patients
      with relapsed or refractory relapsed or refractory follicular (FL) or marginal one (MZL)
      lymphoma.
This is a phase II, multicenter study to assess the efficacy and safety of SHC014748M, an
      oral inhibitor of PI3K delta, in patients with relapsed or refractory relapsed or refractory
      follicular (FL) or marginal one (MZL) lymphoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: up to 12 months
description: Proportion of patients who have either a complete or partial response before any treatment change.
measure: Lymph Node Response (LNR)
time frame: up to 12 months
description: LNR was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the product of the perpendicular diameters (SPD) of measurable index lesions.
measure: Time to Response (TTR)
time frame: up to 12 months
description: TTR was defined as the interval from the start of SHC014748M treatment to the first documentation of complete response(CR) or partial response(PR).
measure: Progression-Free Survival (PFS)
time frame: up to 12 months
description: PFS was defined as the interval from the start of SHC014748M treatment to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using Kaplan-Meier (KM) estimates.
measure: Duration of Response (DOR)
time frame: up to 12 months
description: DOR was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression as or death from any cause. DOR was analyzed using KM estimates.
measure: Mean Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Scale.
time frame: up to 12 months
description: The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on health related quality of life(HRQL) and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess non-Hodgkins lymphoma(NHL) related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). Higher scores are associated with a better quality of life.
measure: Safety and Tolerability of SHC014748M Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms.
time frame: up to 12 months
measure: Pharmacokinetics Parameter: Cmax
time frame: 4 weeks
measure: Pharmacokinetics Parameter: Tmax
time frame: 4 weeks
measure: Pharmacokinetics Parameter: ACUlast
time frame: 4 weeks
arm group label: SHC014748M treatment
arm group type: Experimental
description: SHC014748M capsule, 200mg QD, 28 days for each cycle
intervention type: Drug
intervention name: SHC014748M
description: Each treatment cycle is comprised of 28-day consecutive dosing of SHC014748M, 200mg QD (Days 1 to28). Upon completion of each cycle, patients may continue to receive oral SHC014748M if they can benefit from the treatment and the toxicity is tolerable.
arm group label: SHC014748M treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jianyong Li, MD
role: Principal Investigator
affiliation: The First Affiliated Hospital with Nanjing Medical University
last name: Chao Wang
phone: 13851803148
email: wangchao@sanhome.com
last name: Hongchan Zhang
phone: 15150516871
email: zhanghcyf@sanhome.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell, Marginal Zone
sharing ipd: No