xml: <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/NCT05979857</url>
    </required_header>
    <id_info>
      <org_study_id>SALA-003-NHL</org_study_id>
      <nct_id>NCT05979857</nct_id>
    </id_info>
    <brief_title>Study of SP-3164 in Relapsed or Refractory Non-Hodgkin's Lymphoma</brief_title>
    <official_title>A Phase 1, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SP-3164 in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Salarius Pharmaceuticals, LLC</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Salarius Pharmaceuticals, LLC</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>
        The purpose of this research is to help researchers find out if SP-3164 is safe and if it may&#xD;
        be of benefit in the treatment of patients with Non-Hodgkin's lymphoma that has progressed&#xD;
        after prior treatment, or that never responded to previous treatment.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        SALA-003-NHL is a phase 1 open-label, multicenter, first-in-human study of SP-3164 in&#xD;
        patients with R/R B-cell NHL that will be conducted in two parts. Part 1 is a dose escalation&#xD;
        using a sequential accelerated titration design for the first two dose levels followed by a&#xD;
        3+3 dose escalation design to assess the safety and tolerability of SP-3164 in patients with&#xD;
        R/R B-cell NHL. Upon completion of the dose escalation design and review of all available&#xD;
        safety, tolerability, PK, PD, and preliminary efficacy data the Safety Review Committee (SRC)&#xD;
        will recommend two dose levels for the randomized dose selection optimization (Part 2). The&#xD;
        dose selection optimization will randomize 1:1 approximately 30 patients with R/R DLBCL to&#xD;
        the two selected dose levels (15 new patients per dose level) to determine the recommended&#xD;
        phase 2 dose (RP2D) and further characterize safety, tolerability, PK, PD, and preliminary&#xD;
        efficacy data of SP-3164. SP-3164 will be administered orally once daily under fasting&#xD;
        conditions on 7 consecutive on-treatment days followed by 7 consecutive off-treatment days.&#xD;
        One treatment cycle will be defined as 28 days.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 15, 2023</start_date>
    <completion_date type="Anticipated">August 15, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 15, 2024</primary_completion_date>
    <phase>Early Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>This study is a phase 1, open-label, multicenter, dose escalation (part 1) and dose selection optimization (part 2) study of SP-3164 in patients with R/R B-cell NHL.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Dose Escalation: Characterize the Safety of SP-3164</measure>
      <time_frame>4 months</time_frame>
      <description>Dose Escalation (Part 1)&#xD;
  • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Escalation: Assess Dose Limiting Toxicities of SP-3164</measure>
      <time_frame>6 months</time_frame>
      <description>Dose Escalation (Part 1)&#xD;
  • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Escalation: Assess the Maximum Tolerated Dose of SP-3164</measure>
      <time_frame>6 months</time_frame>
      <description>Dose Escalation (Part 1)&#xD;
  • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Optimization: Further characterize the safety of the 2 selected doses of SP-3164 from Part 1 (dose escalation)</measure>
      <time_frame>6 months</time_frame>
      <description>Dose Selection Optimization (Part 2)&#xD;
  • To further characterize the safety of the two selected doses of SP-3164 from part 1 and determine the recommended phase 2 dose (RP2D) of SP-3164 for future studies</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Optimization: Determine the recommended phase 2 dose of SP-3164 for future studies</measure>
      <time_frame>6 months</time_frame>
      <description>• To further characterize the safety of the two selected doses of SP-3164 from part 1 and determine the recommended phase 2 dose (RP2D) of SP-3164 for future studies</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">72</enrollment>
    <condition>Lymphoma, Non-Hodgkin's, Adult</condition>
    <arm_group>
      <arm_group_label>Dose Escalation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>For part 1 dose escalation, one patient per dose cohort will be initially recruited (accelerated titration dose-escalation, single-patient cohorts/dose level) for the first two dose levels or until the first instance of a ≥ Grade 2 toxicity (excluding Grade 2 neutropenia and lymphopenia and adverse events unequivocally due to the underlying disease or to an extraneous cause), or dose-limiting toxicity (DLT), whichever occurs earlier. Further cohorts will be recruited in blocks of three patients, i.e., 3+3 dose escalation design.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose Optimization</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>For part 2 dose selection optimization, two dose levels will be selected by the Safety Review Committee (SRC) based on review of all available data on safety, tolerability, PK, PD, and preliminary efficacy from part 1. The dose selection optimization will include only patients with R/R DLBCL and will randomize 1:1 approximately 30 new patients at the two selected dose levels (15 patients to each of the two selected dose levels) before declaring the RP2D. Assessment of PK/PD of SP-3164 will be included in part 2 dose selection optimization.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SP-3164</intervention_name>
      <description>SP-3164, an oral next generation cereblon-binding molecular glue 'protein degrader'</description>
      <arm_group_label>Dose Escalation</arm_group_label>
      <arm_group_label>Dose Optimization</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Diagnosis (WHO 2016 criteria) of R/R B-cell NHL in dose escalation (part 1) and limited to&#xD;
          R/R DLBCL in dose selection optimization (part 2) confirmed by biopsy and immunophenotyping&#xD;
  &#xD;
          Dose escalation: at time of enrollment, R/R B-cell NHL patients per WHO 2016 criteria&#xD;
          including DLBCL (including low grade transformed lymphoma), mantle cell lymphoma,&#xD;
          follicular lymphoma, and marginal zone lymphoma and must:&#xD;
  &#xD;
            -  require treatment in the opinion of the Investigator&#xD;
  &#xD;
            -  received at least 2 lines of systemic therapy for B-cell NHL&#xD;
  &#xD;
          Dose selection optimization: at time of enrollment, R/R DLBCL (including low grade&#xD;
          transformed lymphoma) patients must have received 2 or 3 lines of systemic therapy for&#xD;
          DLBCL&#xD;
  &#xD;
          o Prior immunomodulatory imide drug (IMiD) therapy is allowed (e.g., lenalidomide)&#xD;
  &#xD;
          Measurable disease per the 2017 International Working Group Consensus Response Evaluation&#xD;
          Criteria for Lymphoma&#xD;
  &#xD;
          Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1&#xD;
  &#xD;
          Existing archival tumor tissue (fresh frozen paraffin embedded [FFPE], 5 unstained slides)&#xD;
          not older than 2 years from Cycle 1 Day 1 or willingness to provide fresh tumor biopsy&#xD;
          during screening&#xD;
  &#xD;
          Normal organ and marrow function, defined by specific laboratory parameters&#xD;
  &#xD;
          Ability to take orally administered medication&#xD;
  &#xD;
          Washout period prior to Cycle 1 Day 1 of SP-3164: at least 21 days or 5 half-lives&#xD;
          (whichever is shorter) from prior systemic anticancer treatment, including chemotherapy,&#xD;
          biologic therapy, small molecule inhibitors, monoclonal antibodies, and any investigational&#xD;
          agents; at least 14 days from palliative radiotherapy if ≤ 10 fractions or total dose ≤ 30&#xD;
          gray (Gy) or at least 28 days from radiotherapy if total dose &gt; 30 Gy; at least 21 days&#xD;
          from major surgery&#xD;
  &#xD;
          Life expectancy of at least 3 months&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Patients with chronic lymphocytic leukemia, high grade B-cell lymphoma, or Richter's&#xD;
          syndrome&#xD;
  &#xD;
          Patients who have not recovered to Grade 1 toxicity or baseline due to any previous&#xD;
          anticancer therapy according to the NCI CTCAE v5.0, excluding Grade 2 alopecia. Lymphopenia&#xD;
          ≤ Grade 2 is allowed&#xD;
  &#xD;
          Patients with primary central nervous system (CNS) lymphoma or active CNS or meningeal&#xD;
          lymphomatous involvement&#xD;
  &#xD;
          Persistent diarrhea or malabsorption of ≥ Grade 2 despite medical management&#xD;
  &#xD;
          Impaired cardiac function or clinically significant cardiac disease, including symptomatic&#xD;
          congestive heart failure, left ventricular ejection fraction (LVEF) &lt; 50%, unstable angina&#xD;
          pectoris or cardiac arrhythmias, baseline QTc (Fridericia) &gt; 450 milliseconds, long QT&#xD;
          syndrome or family history of idiopathic sudden death or congenital long QT syndrome,&#xD;
          myocardial infarct within 6 months of study enrollment, clinically significant pericardial&#xD;
          disease&#xD;
  &#xD;
          Solid organ transplant recipient&#xD;
  &#xD;
          Allogeneic stem cell transplantation (SCT) recipient&#xD;
  &#xD;
          Autologous SCT recipient &lt;100 days from Cycle 1 Day 1 or otherwise not fully recovered from&#xD;
          SCT-related toxicity&#xD;
  &#xD;
          Completion of CAR-T therapy &lt; 90 days from Cycle 1 Day 1&#xD;
  &#xD;
          Systemic immunosuppressants and chronic systemic corticosteroids (at doses ≥ 10 mg/day of&#xD;
          prednisone or equivalent) are prohibited&#xD;
  &#xD;
          Malignant disease, other than that being treated in this study. Note: Patients with basal&#xD;
          cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ&#xD;
          (e.g., breast carcinoma, cervical cancer in situ) who have undergone potentially curative&#xD;
          therapy are not excluded. Other exceptions include malignancies that were treated&#xD;
          curatively and have not recurred within 3 years prior to Cycle 1 Day 1 and any malignancy&#xD;
          considered indolent and that has never required therapy&#xD;
  &#xD;
          Other concurrent severe or uncontrolled concomitant medical conditions that might cause&#xD;
          unacceptable safety risks or compromise compliance with the protocol&#xD;
  &#xD;
          Pregnant and breastfeeding women&#xD;
  &#xD;
          Known history of HIV-positivity; known hepatitis B or hepatitis C virus infection&#xD;
  &#xD;
          Men and women of child-bearing potential unwilling to use adequate contraception according&#xD;
          to study protocol&#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_contact>
      <last_name>Oyeniyi &quot;Rocky&quot; Oyesina, MD</last_name>
      <phone>+1 678 687 9327</phone>
      <email>ooyesina@salariuspharma.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Rebecca Griffith-Eskew</last_name>
      <phone>+1 254 265 2782</phone>
      <email>reskew@salariuspharma.com</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</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</mesh_term>
      <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05979857
  org study id: SALA-003-NHL
  nct id: NCT05979857
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this research is to help researchers find out if SP-3164 is safe and if it may
        be of benefit in the treatment of patients with Non-Hodgkin's lymphoma that has progressed
        after prior treatment, or that never responded to previous treatment.
  SALA-003-NHL is a phase 1 open-label, multicenter, first-in-human study of SP-3164 in
        patients with R/R B-cell NHL that will be conducted in two parts. Part 1 is a dose escalation
        using a sequential accelerated titration design for the first two dose levels followed by a
        3+3 dose escalation design to assess the safety and tolerability of SP-3164 in patients with
        R/R B-cell NHL. Upon completion of the dose escalation design and review of all available
        safety, tolerability, PK, PD, and preliminary efficacy data the Safety Review Committee (SRC)
        will recommend two dose levels for the randomized dose selection optimization (Part 2). The
        dose selection optimization will randomize 1:1 approximately 30 patients with R/R DLBCL to
        the two selected dose levels (15 new patients per dose level) to determine the recommended
        phase 2 dose (RP2D) and further characterize safety, tolerability, PK, PD, and preliminary
        efficacy data of SP-3164. SP-3164 will be administered orally once daily under fasting
        conditions on 7 consecutive on-treatment days followed by 7 consecutive off-treatment days.
        One treatment cycle will be defined as 28 days.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: This study is a phase 1, open-label, multicenter, dose escalation (part 1) and dose selection optimization (part 2) study of SP-3164 in patients with R/R B-cell NHL.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose Escalation: Characterize the Safety of SP-3164
  time frame: 4 months
  description: Dose Escalation (Part 1)
  • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164
  measure: Dose Escalation: Assess Dose Limiting Toxicities of SP-3164
  time frame: 6 months
  description: Dose Escalation (Part 1)
  • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164
  measure: Dose Escalation: Assess the Maximum Tolerated Dose of SP-3164
  time frame: 6 months
  description: Dose Escalation (Part 1)
  • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164
  measure: Dose Optimization: Further characterize the safety of the 2 selected doses of SP-3164 from Part 1 (dose escalation)
  time frame: 6 months
  description: Dose Selection Optimization (Part 2)
  • To further characterize the safety of the two selected doses of SP-3164 from part 1 and determine the recommended phase 2 dose (RP2D) of SP-3164 for future studies
  measure: Dose Optimization: Determine the recommended phase 2 dose of SP-3164 for future studies
  time frame: 6 months
  description: • To further characterize the safety of the two selected doses of SP-3164 from part 1 and determine the recommended phase 2 dose (RP2D) of SP-3164 for future studies
  arm group label: Dose Escalation
  arm group type: Experimental
  description: For part 1 dose escalation, one patient per dose cohort will be initially recruited (accelerated titration dose-escalation, single-patient cohorts/dose level) for the first two dose levels or until the first instance of a ≥ Grade 2 toxicity (excluding Grade 2 neutropenia and lymphopenia and adverse events unequivocally due to the underlying disease or to an extraneous cause), or dose-limiting toxicity (DLT), whichever occurs earlier. Further cohorts will be recruited in blocks of three patients, i.e., 3+3 dose escalation design.
  arm group label: Dose Optimization
  arm group type: Experimental
  description: For part 2 dose selection optimization, two dose levels will be selected by the Safety Review Committee (SRC) based on review of all available data on safety, tolerability, PK, PD, and preliminary efficacy from part 1. The dose selection optimization will include only patients with R/R DLBCL and will randomize 1:1 approximately 30 new patients at the two selected dose levels (15 patients to each of the two selected dose levels) before declaring the RP2D. Assessment of PK/PD of SP-3164 will be included in part 2 dose selection optimization.
  intervention type: Drug
  intervention name: SP-3164
  description: SP-3164, an oral next generation cereblon-binding molecular glue 'protein degrader'
  arm group label: Dose Escalation
  arm group label: Dose Optimization
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Oyeniyi "Rocky" Oyesina, MD
  phone: +1 678 687 9327
  email: ooyesina@salariuspharma.com
  last name: Rebecca Griffith-Eskew
  phone: +1 254 265 2782
  email: reskew@salariuspharma.com
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Lymphoma, Non-Hodgkin
  sharing ipd: No