<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/NCT04463615</url>
  </required_header>
  <id_info>
    <org_study_id>19606</org_study_id>
    <secondary_id>NCI-2020-02973</secondary_id>
    <secondary_id>19606</secondary_id>
    <secondary_id>P30CA033572</secondary_id>
    <nct_id>NCT04463615</nct_id>
  </id_info>
  <brief_title>Leflunomide for the Treatment of Relapsed or Refractory CD30+ Lymphoproliferative Disorders</brief_title>
  <official_title>Pilot Trial of Leflunomide in Patients With CD30+ Lymphoproliferative Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>City of Hope Medical Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial studies how well leflunomide works for the treatment of patients with CD30+&#xD;
      lymphoproliferative disorders that have come back (relapsed) or do not respond to treatment&#xD;
      (refractory). Leflunomide may stop the growth of cancer cells by blocking some of the enzymes&#xD;
      needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate overall response rate of leflunomide treatment.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess complete response rate and duration of response of leflunomide treatment.&#xD;
&#xD;
      II. To assess toxicities of leflunomide treatment. III. To assess disease status by the CAILS&#xD;
      (composite assessment of index lesion severity).&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. To generate a preliminary ribonucleic acid (RNA) signature associated with response of&#xD;
      CD30+ lymphoproliferative disorders (LYPDs) cells to leflunomide.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive leflunomide orally (PO) once daily (QD) on days 1-28. Treatment repeats&#xD;
      every 28 days for up to 13 cycles in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 5, 2021</start_date>
  <completion_date type="Anticipated">July 16, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 16, 2023</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>Overall response rate</measure>
    <time_frame>Up to 12 months post treatment</time_frame>
    <description>Defined as the proportion of patients with a documented response (complete response [CR] or partial [PR]) any time during study treatment. Response will be categorized by modified severity weighted assessment tool (mSWAT). Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete response rate</measure>
    <time_frame>Up to 12 months post treatment</time_frame>
    <description>Defined as the proportion of patients with a documented CR any time during study treatment. Response will be assessed by mSWAT. Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Up to 12 months post treatment</time_frame>
    <description>Will be calculated using Kaplan-Meier product limit estimator; median duration of response will also be estimated when possible.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>From the date of first documented response (CR or PR) to the first documented disease progression or death, whichever occurs first, assessed up to 12 months</time_frame>
    <description>Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities will be summarized, in terms of type, grade, time of onset, duration, and attribution to the study treatment.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Micro (mi)R ribonucleic acid (RNA)/messenger (m)RNA expression profile</measure>
    <time_frame>Up to 12 months post treatment</time_frame>
    <description>Data will be summarized by descriptive statistics. The data will also be used to explore the miRNA/mRNA that show significant differences between responders and non-responders after leflunomide treatment. For miRNA/RNA profiling, fold changes &gt; 3 with an false discovery rate (FDR) &lt; 0.05 will be considered significant.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Recurrent Lymphoproliferative Disorder</condition>
  <condition>Refractory Lymphoproliferative Disorder</condition>
  <arm_group>
    <arm_group_label>Treatment (leflunomide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive leflunomide PO QD on days 1-28. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leflunomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (leflunomide)</arm_group_label>
    <other_name>Arava</other_name>
    <other_name>SU101</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented informed consent of the participant and/or legally authorized&#xD;
             representative&#xD;
&#xD;
               -  Assent, when appropriate, will be obtained per institutional guidelines&#xD;
&#xD;
          -  Patients must have a life expectancy of &gt; 3 months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) =&lt; 2&#xD;
&#xD;
          -  Patients must have a diagnosis of cutaneous CD30+ LYPD&#xD;
&#xD;
          -  Patients must be relapsed or are refractory to at least 1 prior line of therapy&#xD;
&#xD;
          -  At least 2 weeks from prior therapy to time of start of treatment. Prior therapy&#xD;
             includes steroids (except prednisone or equivalent - up to 10 mg/day is allowed)&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/mm^3 (within 21 days prior to day 1 of&#xD;
             protocol therapy). NOTE: Growth factor is not permitted within 14 days of ANC&#xD;
             assessment unless cytopenia is secondary to disease involvement&#xD;
&#xD;
          -  Platelets &gt;= 50,000/mm^3 (within 21 days prior to day 1 of protocol therapy). NOTE:&#xD;
             Platelet transfusions are not permitted within 14 days of platelet assessment unless&#xD;
             cytopenia is secondary to disease involvement&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)&#xD;
             (within 21 days prior to day 1 of protocol therapy)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) =&lt; 2.0 x ULN (within 21 days prior to Day 1 of&#xD;
             protocol therapy)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) =&lt; 2.0 x ULN (within 21 days prior to day 1 of protocol&#xD;
             therapy)&#xD;
&#xD;
          -  Creatinine clearance of &gt;= 30 mL/min per 24 hour urine test or the Cockcroft-Gault&#xD;
             formula (within 21 days prior to day 1 of protocol therapy)&#xD;
&#xD;
          -  Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo,&#xD;
             hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative)&#xD;
             (within 21 days prior to day 1 of protocol therapy)&#xD;
&#xD;
               -  If positive, hepatitis C RNA quantitation must be performed&#xD;
&#xD;
          -  Meets other institutional and federal requirements for infectious disease titer&#xD;
             requirements. Note infectious disease testing to be performed within 28 days prior to&#xD;
             day 1 of protocol therapy&#xD;
&#xD;
          -  Negative for tuberculosis antigen (e.g. T-Spot test)&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP): negative urine or serum pregnancy test&#xD;
             (within 21 days prior to day 1 of protocol therapy). If the urine test is positive or&#xD;
             cannot be confirmed as negative, a serum pregnancy test will be required&#xD;
&#xD;
          -  Agreement by females and males of childbearing potential* to use an effective method&#xD;
             of birth control (hormonal or barrier method of birth control or abstinence) or&#xD;
             abstain from heterosexual activity for the course of the study through at least three&#xD;
             months after the last dose of protocol therapy. The effects of study treatment on a&#xD;
             developing fetus have the potential for teratogenic or abortifacient effects. Should a&#xD;
             woman become pregnant or suspect that she is pregnant while participating on the&#xD;
             trial, she should inform her treating physician immediately&#xD;
&#xD;
               -  Childbearing potential defined as not being surgically sterilized (men and women)&#xD;
                  or have not been free from menses for &gt; 2 years (women only)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or planned use of other investigational agents, or concurrent biological,&#xD;
             chemotherapy, or radiation therapy during the study treatment period&#xD;
&#xD;
          -  Current or planned growth factor or transfusion support. If growth factor or&#xD;
             transfusion support is provided between screening and start of treatment, the&#xD;
             participant will no longer be eligible&#xD;
&#xD;
          -  Prior allogeneic transplant&#xD;
&#xD;
          -  Acute active infection requiring systemic therapy within 2 weeks prior to enrollment&#xD;
&#xD;
          -  Known history of hepatitis B or hepatitis C infection&#xD;
&#xD;
          -  Known HIV infection&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to leflunomide or cholestyramine&#xD;
&#xD;
          -  Non-hematologic malignancy within the past 3 years aside from the following&#xD;
             exceptions:&#xD;
&#xD;
               -  Adequately treated basal cell or squamous cell skin cancer&#xD;
&#xD;
               -  Carcinoma in situ of the cervix&#xD;
&#xD;
               -  Prostate cancer &lt; Gleason grade 6 with a stable prostate specific antigen (PSA)&#xD;
&#xD;
               -  Successfully treated in situ carcinoma of the breast&#xD;
&#xD;
          -  Clinically significant medical disease or condition that, in the investigator's&#xD;
             opinion, may interfere with protocol adherence or the patient's ability to give&#xD;
             informed consent&#xD;
&#xD;
          -  Pregnant women and women who are lactating. Leflunomide has potential for teratogenic&#xD;
             or abortifacient effects. Because there is a potential risk for adverse events in&#xD;
             nursing infants secondary to treatment of the mother with these agents, breastfeeding&#xD;
             should be discontinued if the mother is enrolled on this study&#xD;
&#xD;
          -  Any other condition that would, in the investigator's judgment, contraindicate the&#xD;
             patient's participation in the clinical study due to safety concerns or compliance&#xD;
             with clinical study procedures, e.g., infection/inflammation, intestinal obstruction,&#xD;
             unable to swallow medication, social/ psychological issues, etc&#xD;
&#xD;
          -  Prospective participants who, in the opinion of the investigator, may not be able to&#xD;
             comply with all study procedures (including compliance issues related to&#xD;
             feasibility/logistics)&#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>Farah R Abdulla</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</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>Lymphoproliferative Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leflunomide</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>March 30, 2023</submitted>
    <returned>April 19, 2023</returned>
    <submitted>June 20, 2023</submitted>
    <returned>July 11, 2023</returned>
    <submitted>September 14, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04463615
org study id: 19606
secondary id: NCI-2020-02973
secondary id: 19606
secondary id: P30CA033572
nct id: NCT04463615
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This trial studies how well leflunomide works for the treatment of patients with CD30+
      lymphoproliferative disorders that have come back (relapsed) or do not respond to treatment
      (refractory). Leflunomide may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth.
PRIMARY OBJECTIVE:

      I. To evaluate overall response rate of leflunomide treatment.

      SECONDARY OBJECTIVES:

      I. To assess complete response rate and duration of response of leflunomide treatment.

      II. To assess toxicities of leflunomide treatment. III. To assess disease status by the CAILS
      (composite assessment of index lesion severity).

      EXPLORATORY OBJECTIVE:

      I. To generate a preliminary ribonucleic acid (RNA) signature associated with response of
      CD30+ lymphoproliferative disorders (LYPDs) cells to leflunomide.

      OUTLINE:

      Patients receive leflunomide orally (PO) once daily (QD) on days 1-28. Treatment repeats
      every 28 days for up to 13 cycles in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 3 months for 12 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate
time frame: Up to 12 months post treatment
description: Defined as the proportion of patients with a documented response (complete response [CR] or partial [PR]) any time during study treatment. Response will be categorized by modified severity weighted assessment tool (mSWAT). Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals.
measure: Complete response rate
time frame: Up to 12 months post treatment
description: Defined as the proportion of patients with a documented CR any time during study treatment. Response will be assessed by mSWAT. Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals.
measure: Duration of response
time frame: Up to 12 months post treatment
description: Will be calculated using Kaplan-Meier product limit estimator; median duration of response will also be estimated when possible.
measure: Incidence of adverse events
time frame: From the date of first documented response (CR or PR) to the first documented disease progression or death, whichever occurs first, assessed up to 12 months
description: Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities will be summarized, in terms of type, grade, time of onset, duration, and attribution to the study treatment.
measure: Micro (mi)R ribonucleic acid (RNA)/messenger (m)RNA expression profile
time frame: Up to 12 months post treatment
description: Data will be summarized by descriptive statistics. The data will also be used to explore the miRNA/mRNA that show significant differences between responders and non-responders after leflunomide treatment. For miRNA/RNA profiling, fold changes > 3 with an false discovery rate (FDR) < 0.05 will be considered significant.
arm group label: Treatment (leflunomide)
arm group type: Experimental
description: Patients receive leflunomide PO QD on days 1-28. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Leflunomide
description: Given PO
arm group label: Treatment (leflunomide)
other name: Arava
other name: SU101
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Farah R Abdulla
role: Principal Investigator
affiliation: City of Hope Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoproliferative Disorders
mesh term: Leflunomide
submitted: March 30, 2023
returned: April 19, 2023
submitted: June 20, 2023
returned: July 11, 2023
submitted: September 14, 2023