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/NCT05971251</url>
    </required_header>
    <id_info>
      <org_study_id>IRB-300009213</org_study_id>
      <nct_id>NCT05971251</nct_id>
    </id_info>
    <brief_title>Addition of Loncastuximab Tesirine to Acalbrutinib , Chronic Lymphocytic Leukemia</brief_title>
    <official_title>Addition of loNcasTuxImab teSirine to AcalabruTinib in Chronic Lymphocytic Leukemia(Anti-Static Study)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Mayur Narkhede</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>ADC Therapeutics S.A.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Alabama at Birmingham</source>
    <oversight_info>
      <has_dmc>Yes</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>
        Study is a phase I study to determine the maximum tolerated dose of adding Loncastuximab&#xD;
        Tesirine to Aclabrutinib in the treatment of chronic lymphocytic leukemia.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study is a phase I study which will employ the Bayesian optimal interval (BOIN) design to&#xD;
        find the maximum tolerated dose (MTD).&#xD;
  &#xD;
        Approximately 24 Dose-Limiting Toxicity (DLT) evaluable participants will be treated to find&#xD;
        MTD with a target DLT rate of 25%, and 4 pre-specified doses. The total number of&#xD;
        participants enrolled will depend on the frequency of DLTs and when the MTD is determined.&#xD;
        The maximum number of patients at a given dose level is 12.&#xD;
  &#xD;
        The dose of acalabrutinib will be fixed and loncastuximab tesirine will be titrated as in&#xD;
        dose level table 1 below.&#xD;
  &#xD;
        Table 1. Dose levels Dose Level Schedule&#xD;
  &#xD;
          1. 45 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID&#xD;
  &#xD;
          2. 60 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID&#xD;
  &#xD;
          3. 75 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID&#xD;
  &#xD;
          4. 90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent&#xD;
             cycles) + Acalabrutinib 100 mg BID&#xD;
  &#xD;
        The DLT evaluation period is two cycles (42 days).&#xD;
  &#xD;
        Loncastuximab Tesirine will be given as an IV infusion, each cycle is a 21 day cycle, with&#xD;
        Loncastuximab Tesirine given day 1 of each cycle.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">May 2025</completion_date>
    <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
    <phase>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>Sequential dose escalation based on Dose escalation guidelines.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Primary Objective</measure>
      <time_frame>12 months</time_frame>
      <description>Recommended phase 2 dose of loncastuximab tesirine in combination with acalabrutinib</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Secondary Objective 1</measure>
      <time_frame>6 months</time_frame>
      <description>undetectable measurable residual disease rate (uMRD) at 6 months of combination therapy in peripheral blood by NGS based clonoseq test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Objective 2</measure>
      <time_frame>12 months</time_frame>
      <description>Undetectable measurable residual disease rate (uMRD) at 12 months of combination therapy by NGS based clonoseq test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Objective 3</measure>
      <time_frame>12 months</time_frame>
      <description>Best Overall response rate (ORR = CR+CRi+PR) of loncastuximab tesirine in combination with acalabrutinib</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Objective 4</measure>
      <time_frame>12 months</time_frame>
      <description>Complete response rate (CRR= CR + CRi) of loncastuximab tesirine in combination with acalabrutinib in achieving a complete response.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Objective 5</measure>
      <time_frame>12 months</time_frame>
      <description>Progression free survival (PFS) at 12 months after completion of all treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Objective 6</measure>
      <time_frame>12 months</time_frame>
      <description>Incidence of adverse events (AE) of loncastuximab tesirine in combination with acalabrutinib.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Objective 7</measure>
      <time_frame>12 months</time_frame>
      <description>Duration of response (DOR) of loncastuximab tesirine in combination with acalabrutinib</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">24</enrollment>
    <condition>Chronic Lymphocytic Leukemia</condition>
    <arm_group>
      <arm_group_label>Dose Level 1:</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>45 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose Level 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>60 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose Level 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>75 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose level 4:</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent 10 cycles) + Acalabrutinib 100 mg BID for a total of 12 cycles.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Loncastuximab Tesirine and Acalabrutinib</intervention_name>
      <description>Will be given on Day 1 of each cycle with each cycle being 21 days, and is being added to BID Acalabrutinib</description>
      <arm_group_label>Dose Level 1:</arm_group_label>
      <arm_group_label>Dose Level 2</arm_group_label>
      <arm_group_label>Dose Level 3</arm_group_label>
      <arm_group_label>Dose level 4:</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          - Inclusion Criteria For all patients&#xD;
  &#xD;
            1. Diagnosis of CLL according to the IwCLL criteria or SLL according to the World Health&#xD;
               Organization (WHO) criteria. This includes previous documentation of:&#xD;
  &#xD;
                 -  Biopsy-proven small lymphocytic lymphoma OR&#xD;
  &#xD;
                 -  Diagnosis of CLL according to the IWCLL criteria as evidenced by Peripheral blood&#xD;
                    lymphocyte count of greater than 5 x109/L .&#xD;
  &#xD;
                 -  Immunophenotype consistent with CLL defined as the predominant population of&#xD;
                    lymphocytes share both B cell antigens (CD19, CD20 (typically dim expression), or&#xD;
                    CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc).&#xD;
  &#xD;
            2. On therapy with acalabrutinib for a minimum of 3 months without evidence of&#xD;
               progression as per IWCLL 2018 criteria.&#xD;
  &#xD;
            3. Relapsed or Refractory CLL who have received at least one prior therapy before&#xD;
               initiation of acalabrutinib&#xD;
  &#xD;
            4. Presence of measurable residual disease in the peripheral blood or bone marrow&#xD;
               aspirate by NGS based clonoseq test.&#xD;
  &#xD;
            5. Adequate organ function as defined below unless attributed to disease involvement:&#xD;
  &#xD;
                 -  Liver function (bilirubin ≤ 1.5 × ULN, AST and/or ALT &lt;3 x ULN). Patients with&#xD;
                    Gilbert Disease are permitted irrespective of bilirubin values.&#xD;
  &#xD;
                 -  Kidney function (crcl &gt; 30ml/min using Cockroft-Gault, based on actual weight).&#xD;
  &#xD;
                 -  ANC ≥ 1,000/µL, Hgb &gt; 8, Platelet Count ≥ 50,000/ µL. Use of G-CSF is not&#xD;
                    permitted for up to 7 days prior to enrollment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Exclusion Criteria For all patients&#xD;
  &#xD;
                 1. Current evidence of central nervous system involvement.&#xD;
  &#xD;
                 2. Unable to generate clonoseq ID specimen for measurable residual disease tracking.&#xD;
  &#xD;
                 3. Completion of an autologous hematopoietic stem cell transplantation within 3&#xD;
                    months prior to first dose of study drug.&#xD;
  &#xD;
                 4. Prior allogeneic stem cell transplant within 6 months. The patient should not&#xD;
                    have any active Graft vs. Host disease (GVH) or should be on immune suppressive&#xD;
                    agents.&#xD;
  &#xD;
                 5. Completion of treatment with any radiotherapy, chemotherapy, antibody,&#xD;
                    immunoconjugates and/or another investigational drug ≤4 weeks (or 5 half-lives of&#xD;
                    the drug, whichever is shorter) prior to the first dose of study drug. Patients&#xD;
                    may be enrolled after a minimum of 2 weeks of radiation if radiation was for&#xD;
                    palliative intent.&#xD;
  &#xD;
                 6. Progression of disease on BTK inhibitor.&#xD;
  &#xD;
                 7. Unable to tolerate full dose of acalabrutinib at 100 mg twice a day.&#xD;
  &#xD;
                 8. Inability to swallow and retain oral medications.&#xD;
  &#xD;
                 9. Pregnant women are excluded from this study.&#xD;
  &#xD;
                10. Any active, concurrent, significant illness or disease (other underlying&#xD;
                    lymphoma) or clinically significant findings including psychiatric and behavioral&#xD;
                    problems, medical history and/or physical examination findings that would&#xD;
                    preclude the patient from participation in the study such as:&#xD;
  &#xD;
                      -  active infection requiring systemic therapy ≤10 days before the first dose&#xD;
                         of study drug&#xD;
  &#xD;
                      -  unstable angina pectoris, symptomatic congestive heart failure (New York&#xD;
                         Heart Association [NYHA] II, III, IV;), myocardial infarction ≤6 months&#xD;
                         prior to first study drug, uncontrolled cardiac arrhythmia e.g., atrial&#xD;
                         fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose&#xD;
                         of study drug&#xD;
  &#xD;
                      -  Significant (as defined by study doctor) pulmonary disease or disorder&#xD;
  &#xD;
                      -  any severe or uncontrolled other disease or condition which might increase&#xD;
                         the risk associated with study participation&#xD;
  &#xD;
                11. Vaccination with live, attenuated vaccines within 28 days prior to the first dose&#xD;
                    of study medication.&#xD;
  &#xD;
                12. Receiving systemic immunosuppressive medications (including, but not limited to,&#xD;
                    cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor&#xD;
                    necrosis factor agents). The use of inhaled corticosteroids is permitted.&#xD;
  &#xD;
                13. Corticosteroids ≥ 10 mg of prednisone within the last 7 days.&#xD;
  &#xD;
                14. Has had a solid organ transplant within the last 3 years. Note: Patients who have&#xD;
                    had a Solid organ transplant &gt;3 years ago are eligible if there are no&#xD;
                    signs/symptoms of graft versus host disease (GvHD) and off immunosuppressive&#xD;
                    medications as per above.&#xD;
  &#xD;
                15. Known history of hypersensitivity to loncastuximab tesirine&#xD;
  &#xD;
                16. Clinically significant third space fluid accumulation (i.e., ascites requiring&#xD;
                    drainage or pleural effusion that is either requiring drainage or associated with&#xD;
                    shortness of breath)&#xD;
  &#xD;
                17. Breastfeeding or pregnant&#xD;
  &#xD;
                18. Any other malignancy known to be active, with the exception of&#xD;
  &#xD;
                      -  Cervical carcinoma of Stage 1A (1A1,1A2) and 1B (1B1,1B2,1B3)&#xD;
  &#xD;
                      -  Non-invasive basal cell or squamous cell skin carcinoma&#xD;
  &#xD;
                      -  Non-invasive, superficial bladder cancer&#xD;
  &#xD;
                      -  Prostate cancer with a current PSA level &lt; 0.1 ng/mL&#xD;
  &#xD;
                      -  Any curable or localized cancer with a CR of &gt; 2 years' duration.&#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>Mayur Narkhede, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Alabama at Birmingham</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Pamela M Hardwick</last_name>
      <phone>2059755387</phone>
      <email>pamdixon@uab.edu</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
      <investigator_full_name>Mayur Narkhede</investigator_full_name>
      <investigator_title>Assistant Professor, Department of Medicine</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Leukemia, Lymphoid</mesh_term>
      <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Acalabrutinib</mesh_term>
      <mesh_term>Loncastuximab tesirine</mesh_term>
    </intervention_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/NCT05971251
  org study id: IRB-300009213
  nct id: NCT05971251
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  Study is a phase I study to determine the maximum tolerated dose of adding Loncastuximab
        Tesirine to Aclabrutinib in the treatment of chronic lymphocytic leukemia.
  The study is a phase I study which will employ the Bayesian optimal interval (BOIN) design to
        find the maximum tolerated dose (MTD).
  
        Approximately 24 Dose-Limiting Toxicity (DLT) evaluable participants will be treated to find
        MTD with a target DLT rate of 25%, and 4 pre-specified doses. The total number of
        participants enrolled will depend on the frequency of DLTs and when the MTD is determined.
        The maximum number of patients at a given dose level is 12.
  
        The dose of acalabrutinib will be fixed and loncastuximab tesirine will be titrated as in
        dose level table 1 below.
  
        Table 1. Dose levels Dose Level Schedule
  
          1. 45 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
  
          2. 60 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
  
          3. 75 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
  
          4. 90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent
             cycles) + Acalabrutinib 100 mg BID
  
        The DLT evaluation period is two cycles (42 days).
  
        Loncastuximab Tesirine will be given as an IV infusion, each cycle is a 21 day cycle, with
        Loncastuximab Tesirine given day 1 of each cycle.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: Sequential dose escalation based on Dose escalation guidelines.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Primary Objective
  time frame: 12 months
  description: Recommended phase 2 dose of loncastuximab tesirine in combination with acalabrutinib
  measure: Secondary Objective 1
  time frame: 6 months
  description: undetectable measurable residual disease rate (uMRD) at 6 months of combination therapy in peripheral blood by NGS based clonoseq test
  measure: Secondary Objective 2
  time frame: 12 months
  description: Undetectable measurable residual disease rate (uMRD) at 12 months of combination therapy by NGS based clonoseq test.
  measure: Secondary Objective 3
  time frame: 12 months
  description: Best Overall response rate (ORR = CR+CRi+PR) of loncastuximab tesirine in combination with acalabrutinib
  measure: Secondary Objective 4
  time frame: 12 months
  description: Complete response rate (CRR= CR + CRi) of loncastuximab tesirine in combination with acalabrutinib in achieving a complete response.
  measure: Secondary Objective 5
  time frame: 12 months
  description: Progression free survival (PFS) at 12 months after completion of all treatment.
  measure: Secondary Objective 6
  time frame: 12 months
  description: Incidence of adverse events (AE) of loncastuximab tesirine in combination with acalabrutinib.
  measure: Secondary Objective 7
  time frame: 12 months
  description: Duration of response (DOR) of loncastuximab tesirine in combination with acalabrutinib
  arm group label: Dose Level 1:
  arm group type: Experimental
  description: 45 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles
  arm group label: Dose Level 2
  arm group type: Experimental
  description: 60 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles
  arm group label: Dose Level 3
  arm group type: Experimental
  description: 75 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles
  arm group label: Dose level 4:
  arm group type: Experimental
  description: 90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent 10 cycles) + Acalabrutinib 100 mg BID for a total of 12 cycles.
  intervention type: Drug
  intervention name: Loncastuximab Tesirine and Acalabrutinib
  description: Will be given on Day 1 of each cycle with each cycle being 21 days, and is being added to BID Acalabrutinib
  arm group label: Dose Level 1:
  arm group label: Dose Level 2
  arm group label: Dose Level 3
  arm group label: Dose level 4:
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Mayur Narkhede, M.D.
  role: Principal Investigator
  affiliation: University of Alabama at Birmingham
  last name: Pamela M Hardwick
  phone: 2059755387
  email: pamdixon@uab.edu
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Alabama at Birmingham
  investigator full name: Mayur Narkhede
  investigator title: Assistant Professor, Department of Medicine
  mesh term: Leukemia
  mesh term: Leukemia, Lymphoid
  mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
  mesh term: Acalabrutinib
  mesh term: Loncastuximab tesirine
  sharing ipd: No