<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/NCT03264131</url>
  </required_header>
  <id_info>
    <org_study_id>LCCC1637</org_study_id>
    <nct_id>NCT03264131</nct_id>
  </id_info>
  <brief_title>BV-CHEP Chemotherapy for Adult T-cell Leukemia or Lymphoma</brief_title>
  <official_title>Brentuximab Vedotin With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP) for the Treatment of Adult T-Cell Leukemia/Lymphoma: A Pilot Study of the Rare Lymphoma Working Group</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNC Lineberger Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>UNC Lineberger Comprehensive Cancer 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Adult T-cell leukemia/lymphoma (ATLL) is a rare form of cancer found mostly among people from&#xD;
      the Caribbean islands, Western Africa, Brazil, Iran, and Japan. Most cases of this disease in&#xD;
      the United States occur along the East Coast due to emigration from the Caribbean islands.&#xD;
      There is currently no standard treatment for ATLL. Research shows that patients who go into&#xD;
      first time remission (respond completely or partially to treatment) and have a bone marrow&#xD;
      transplant have the best outcomes. Traditional chemotherapy treatments have generally not&#xD;
      worked well in patients with ATLL. Additionally, not all patients will be eligible for a bone&#xD;
      marrow transplant.&#xD;
&#xD;
      The purpose of this study is to see how well individuals with ATLL respond to an&#xD;
      investigational cancer treatment. This investigational treatment combines a drug called&#xD;
      brentuximab vedotin with a standard chemotherapy treatment made up of cyclophosphamide,&#xD;
      doxorubicin, etoposide, and prednisone. This treatment is considered investigational because&#xD;
      it is not approved by the United States Food and Drug Administration (FDA) for the treatment&#xD;
      of ATLL.&#xD;
&#xD;
      Brentuximab vedotin, also known as Adcetris, is approved by the United States Food and Drug&#xD;
      Administration (FDA) for treatment of certain types of lymphomas, including peripheral T-cell&#xD;
      lymphomas when combined with cyclophosphamide, doxorubicin, and prednisone in patients whose&#xD;
      cancer cells express a type of marker called CD30.&#xD;
&#xD;
      Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it.&#xD;
      Antibodies are proteins that are part of the immune system. They can stick to and attack&#xD;
      specific targets on cancer cells. The antibody part of brentuximab vedotin sticks to a target&#xD;
      called cluster of differentiation 30 (CD30) that is located on the outside of the cancer&#xD;
      cells. Normal cells have little or no CD30 on their surface. ATLL cancer cells often have a&#xD;
      larger amount of CD30 on their surface than normal cells. However, CD30 is found in different&#xD;
      amounts on ATLL cancer cells. This study will also test the amount of CD30 found on each&#xD;
      participant's cancer cells. Researchers will be looking to see if the response to the study&#xD;
      treatment varies based on the amount of CD30 found on the outside participants' cancer cells.&#xD;
&#xD;
      In another study, brentuximab vedotin was combined in another study with cyclophosphamide,&#xD;
      doxorubicin, and prednisone. The study included patients with various types of T-cell&#xD;
      lymphomas. Two of the patients enrolled in that study had ATLL. Both had a complete response&#xD;
      (no evidence of disease). The researchers in this study (LCCC 1637) have added etoposide to&#xD;
      the combination of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone.&#xD;
      They predict that the addition of etoposide will improve patient outcomes. Research shows&#xD;
      that etoposide helps improve outcomes in patients with certain types of T-cell lymphomas who&#xD;
      undergo chemotherapy treatment. This investigational combination of brentuximab vedotin with&#xD;
      cyclophosphamide, doxorubicin, etoposide, and prednisone is called BV-CHEP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STUDY OBJECTIVES&#xD;
&#xD;
      Primary Objective To define the proportion of subjects with CR after 4-6 cycles of&#xD;
      brentuximab vedotin in combination with cyclophosphamide, doxorubicin, etoposide, and&#xD;
      prednisone (BV-CHEP) in the treatment of adult T-cell leukemia/lymphoma.&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
      To estimate the overall response rate (ORR) with 4-6 cycles of BV-CHEP therapy in patients&#xD;
      with adult T-cell leukemia/lymphoma.&#xD;
&#xD;
      To determine progression-free survival (PFS) for BV-CHEP in patients with adult T-cell&#xD;
      leukemia/lymphoma who received or did not receive BV maintenance.&#xD;
&#xD;
      To determine duration of response to BV-CHEP in patients with adult T-cell leukemia/lymphoma&#xD;
      who received or did not receive BV maintenance.&#xD;
&#xD;
      To determine overall survival (OS) of patients with adult T-cell leukemia/lymphoma treated&#xD;
      with BV-CHEP who received or did not receive BV maintenance therapy.&#xD;
&#xD;
      To evaluate the toxicity and tolerability of BV-CHEP and BV maintenance therapy via the&#xD;
      National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03).&#xD;
&#xD;
      *Note: After completion or withdrawal from BV-CHEP therapy, patients will segregate into one&#xD;
      of the following groups: 1) those who progressed on BV-CHEP; 2) those who completed 4-6&#xD;
      cycles of BV-CHEP and went on to allogeneic transplant; 3) those who completed 6 cycles of&#xD;
      BV-CHEP but were CD30 negative and ineligible for maintenance therapy; and 4) those who&#xD;
      completed 6 cycles of BV-CHEP, were CD30 positive, but continued study treatment on BV in the&#xD;
      maintenance phase of the study.&#xD;
&#xD;
      ENDPOINTS&#xD;
&#xD;
      Primary Endpoint&#xD;
&#xD;
      Criteria for CR after 4-6 cycles of BV-CHEP will be based on the International Workshop to&#xD;
      standardize response criteria for malignant lymphomas (ie, Lugano Criteria per Cheson, et al.&#xD;
      J Clin Oncol. 2014;32(27):3059-68).&#xD;
&#xD;
      Secondary Endpoints&#xD;
&#xD;
      Criteria for overall response will be based on the International Workshop to standardize&#xD;
      response criteria for malignant lymphomas (ie, Lugano Criteria per Cheson, et al. J Clin&#xD;
      Oncol. 2014;32(27):3059-68).&#xD;
&#xD;
      PFS is defined as time from D1 of treatment until disease progression (based on Lugano&#xD;
      criteria) or death from any cause.&#xD;
&#xD;
      Duration of response is defined as the time from documentation of tumor response per Lugano&#xD;
      criteria to disease progression&#xD;
&#xD;
      OS is defined as the time from D1 of treatment until death from any cause&#xD;
&#xD;
      Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03&#xD;
&#xD;
      TREATMENT INFORMATION&#xD;
&#xD;
      Patients will undergo screening to see if they are eligible. If eligible, participants will&#xD;
      start by receiving 2 cycles of BV-CHEP (cycles 1 and 2). After 2 cycles of BV-CHEP,&#xD;
      participants will have a positron emission tomography/computed tomography (PET/CT) or a CT&#xD;
      scan to assess their disease. If the scan shows the cancer has stayed the same or gotten&#xD;
      better, participants may continue taking BV-CHEP for two more cycles (cycle 3 and 4). If, at&#xD;
      any time during study treatment, a participant's disease gets worse, the participant will end&#xD;
      study treatment and other treatment options will be discussed with you.&#xD;
&#xD;
      If a participant continues on BV-CHEP, at the beginning of cycle 5, the participant will have&#xD;
      a PET/CT scan. If the cancer has gotten better and the participant is eligible for a bone&#xD;
      marrow transplant, he/she will have the transplant. If the participant is not eligible for a&#xD;
      bone marrow transplant and the cancer has stayed the same or gotten better, the participant&#xD;
      may continue on BV-CHEP for two more cycles (cycles 5 and 6).&#xD;
&#xD;
      At the end of cycle 6 of BV-CHEP, participants will have another PET/CT scan. If the scan&#xD;
      shows the cancer has gotten better and the participant is eligible for a bone marrow&#xD;
      transplant, he/she will have the transplant. If a participant is not eligible for a bone&#xD;
      marrow transplant and his/her cancer cells did not test positive for CD30, the participant&#xD;
      will end study treatment. The study doctor will discuss other treatment options that are not&#xD;
      part of this study with the participant.&#xD;
&#xD;
      Participants may continue on brentuximab vedotin alone as maintenance therapy if:&#xD;
&#xD;
        -  They are not eligible for a bone marrow transplant,&#xD;
&#xD;
        -  Their cancer cells tested positive for CD30, and&#xD;
&#xD;
        -  Their cancer has not gotten worse after taking BV-CHEP.&#xD;
&#xD;
      Participants will be removed from BV maintenance therapy if their cancer get worse.&#xD;
&#xD;
      DURATION OF THERAPY Therapy in LCCC 1637 involves up to 6 cycles of treatment with&#xD;
      brentuximab vedotin (BV) with a chemotherapy treatment made up of cyclophosphamide,&#xD;
      doxorubicin, etoposide, and prednisone (CHEP). Each cycle is 21 days long. Participants may&#xD;
      continue on BV alone as maintenance therapy after 6 cycles of BV-CHEP if they meet the&#xD;
      requirements outlined above. Each cycles of BV maintenance therapy is 21-day long. BV&#xD;
      maintenance therapy may continue until a participant's disease progresses.&#xD;
&#xD;
      DURATION OF FOLLOW-UP PERIOD Participants will be followed for survival for up to 5 years.&#xD;
      They will also have a PET/CT or CT scan and a blood test every 6 months for 2 years after&#xD;
      study treatment ends.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 15, 2018</start_date>
  <completion_date type="Anticipated">December 15, 2028</completion_date>
  <primary_completion_date type="Anticipated">December 15, 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>Proportion of subjects with Complete Response after 2-6 cycles of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP)</measure>
    <time_frame>18 weeks</time_frame>
    <description>Criteria for CR after 2-6 cycles of BV-CHEP will be based on the International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR) associated with 2-6 cycles of BV-CHEP therapy in patients with adult T-Cell leukemia/lymphoma.</measure>
    <time_frame>70 weeks</time_frame>
    <description>ORR will be evaluated as the rate of complete responses (CR) + partial responses (PR) as defined by the International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria). Patients with leukemic component to their disease at baseline will be assessed per Adult T-Cell Leukemia/Lymphoma National Comprehensive Cancer Network (NCCN) guidelines version 2.2017</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS) for BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.</measure>
    <time_frame>5 years</time_frame>
    <description>PFS will be assessed from day 1 of treatment until disease progression (based on International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria) or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response to BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.</measure>
    <time_frame>3 years</time_frame>
    <description>Duration of response is defined as the time from documentation of tumor response per Lugano criteria to disease progression. Subjects with a leukemic component to their disease at baseline will have peripheral blood assessed per adult T-cell leukemia/lymphoma NCCN Guidelines version 2.2017</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) of patients with adult T-cell leukemia/lymphoma treated with BV-CHEP who received or did not receive BV maintenance therapy.</measure>
    <time_frame>5 years</time_frame>
    <description>Overall survival is defined as the time from day 1 of treatment until death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity and tolerability of BV-CHEP and BV maintenance therapy via National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4)</measure>
    <time_frame>70 weeks</time_frame>
    <description>Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03, a scale from 1-mild to 5-death.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Lymphoma</condition>
  <condition>Adult T-Cell Leukemia/Lymphoma</condition>
  <condition>Lymphatic Diseases</condition>
  <arm_group>
    <arm_group_label>Open-label, Multicenter, Single-Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is a single-arm intervention where patients will receive concurrent therapy with BV+CHEP [(brentuximab vedotin; 1.8 mg/kg IV, on D1 every 21 days) (cyclophosphamide 750 mg/m^2 on D1; doxorubicin 50 mg/m^2 on D1, etoposide 100 mg/m^2 IV infusion on D1-3; prednisone 100 mg orally once daily on D1-5; cycle length every 21 days)] for 2 to 6 cycles of induction therapy. After 6 cycles of BV + CHEP, responders (CR, PR or SD) who are not eligible for BMT and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV, every 21 days) until disease progression, withdrawal due to toxicity or death.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin</intervention_name>
    <description>Brentuximab Vedotin will be given at 1.8 mg/kg IV over approximately 30 minutes on D1 every 21 days for 2-6 cycles. Responders (CR, PR or SD) who are not eligible for bone marrow transplant (BMT) and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV for approximately 30 minutes, every 21 days).</description>
    <arm_group_label>Open-label, Multicenter, Single-Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHEP</intervention_name>
    <description>Cyclophosphamide- 750 mg/m^2 IV over approximately 1 hour on D1 every 21 days for 2-6 cycles&#xD;
Doxorubicin- 50 mg/m^2 IV over approximately 3-5 minutes on D1 every 21 days for 2-6 cycles.&#xD;
Etoposide - 100 mg/m^2 IV over approximately 1 hour each day for 3 days every 21 days for 2-6 cycles.&#xD;
Prednisone - 100 mg, orally once daily for 5 days every 21 days for 2-6 cycles.</description>
    <arm_group_label>Open-label, Multicenter, Single-Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must meet all of the following inclusion criteria to participate in this study:&#xD;
&#xD;
          1. Informed consent and HIPAA authorization for release of personal health information&#xD;
             obtained.&#xD;
&#xD;
          2. Age ≥ 18 years at the time of consent.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.&#xD;
&#xD;
          4. Histological confirmation of biopsy-proven peripheral T-cell leukemia/lymphoma&#xD;
             consistent with ATLL&#xD;
&#xD;
               -  Included subtypes will be: acute, lymphomatous, and chronic unfavorable. Chronic&#xD;
                  unfavorable is defined as the chronic variant with at least one of the following:&#xD;
                  lactate dehydrogenase (LDH)&gt;upper limit of normal (ULN), blood urea nitrogen&#xD;
                  (BUN)&gt;ULN, Albumin&lt;lower limit of normal (LLN)&#xD;
&#xD;
               -  Positive human T-lymphotropic virus-1 (HTLV-1) antibody testing with confirmatory&#xD;
                  testing via Western blot, enzyme-linked immunosorbent assay (ELISA), or molecular&#xD;
                  testing (PCR).&#xD;
&#xD;
          5. Documented negative serologic testing for human immunodeficiency virus (HIV).&#xD;
&#xD;
          6. If positive for HBV exposure or prior infection, can continue to participate in trial&#xD;
             with prophylactic entecavir (for HBV). If positive for hepatitis c virus (HCV)&#xD;
             exposure or active infection, can participate in trial with monitoring for liver&#xD;
             function abnormalities.&#xD;
&#xD;
          7. Demonstrate adequate organ function as defined below; all screening labs to be&#xD;
             obtained within three days prior to study treatment.&#xD;
&#xD;
             System: Renal -Calculated creatinine clearance&#xD;
&#xD;
             Laboratory Value: ≥ 30 mL/min using the Cockcroft-Gault formula for subjects with&#xD;
             creatinine levels &gt; 2.0 x institutional ULN&#xD;
&#xD;
             System: Hepatic - Bilirubin&#xD;
&#xD;
             Laboratory Value: ≤ 3.0 mg/dL&#xD;
&#xD;
             System: Hepatic - Aspartate aminotransferase (AST)&#xD;
&#xD;
             Laboratory Value: ≤ 2.5 × ULN&#xD;
&#xD;
             System: Hepatic - Alanine aminotransferase (ALT)&#xD;
&#xD;
             Laboratory Value: ≤ 2.5 × ULN&#xD;
&#xD;
          8. Females of childbearing potential must have a negative serum pregnancy test within&#xD;
             three days (72 hours) prior to initiating study treatment. NOTE: Females are&#xD;
             considered of child bearing potential unless they are surgically sterile (have&#xD;
             undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they&#xD;
             are naturally postmenopausal for at least 12 consecutive months.&#xD;
&#xD;
          9. Females of childbearing potential must be willing to abstain from heterosexual&#xD;
             activity or to use 2 forms of effective methods of contraception from the time of&#xD;
             informed consent until 24 weeks (6 months) after treatment discontinuation. The two&#xD;
             contraception methods can be comprised of two barrier methods, or a barrier method&#xD;
             plus a hormonal method or an intrauterine device that meets &lt;1% failure rate for&#xD;
             protection from pregnancy in the product label.&#xD;
&#xD;
         10. Male patients with female partners must have had a prior vasectomy or agree to use an&#xD;
             adequate method of contraception (i.e., double barrier method: condom plus spermicidal&#xD;
             agent) starting with the first dose of study therapy through 24 weeks (6 months) after&#xD;
             the last dose of study therapy.&#xD;
&#xD;
         11. As determined by the enrolling physician or protocol designee, willingness and ability&#xD;
             of the subject to understand and comply with study procedures&#xD;
&#xD;
         12. Prior Treatment: Previously untreated or has received a maximum of one cycle of any&#xD;
             combination chemotherapy (e.g. cyclophosphamide, doxorubicin, vincristine, prednisone&#xD;
             (CHOP), CHOEP, DA-EPOCH, doxorubicin, cyclophosphamide, cytarabine, vincristine,&#xD;
             methotrexate/Etoposide, ifosfamide, cytarabine, methotrexate (CODOX-M/IVAC),&#xD;
             HyperCVAD) within 4 weeks of signing the main consent form. Additionally, a patient&#xD;
             may have taken antiretroviral therapy (e.g. azidothymidine (AZT) and/or IFN) at any&#xD;
             time prior to study enrollment&#xD;
&#xD;
         13. CD30 expression determined by flow cytometry or IHC. NOTE: If CD30 testing was&#xD;
             previously done on the biopsy sample from diagnosis, this information will be&#xD;
             collected. If CD30 testing was not done, an archival sample from the biopsy used for&#xD;
             diagnosis will be requested and tested for CD30. CD30 testing will also be done on the&#xD;
             bone marrow tissue collected from the bone marrow exam. If we are unable to obtain an&#xD;
             archival sample or if the bone marrow exam is negative, a new biopsy will be performed&#xD;
             to confirm the diagnosis and test for CD30.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects who meet any of the following criteria should be excluded from study&#xD;
        participation:&#xD;
&#xD;
          1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the&#xD;
             mother is being treated on study).&#xD;
&#xD;
          2. Has a known additional malignancy that is active and/or progressive requiring&#xD;
             treatment; exceptions include basal cell or squamous cell skin cancer, in situ&#xD;
             cervical or bladder cancer, or other cancer for which the subject has been&#xD;
             disease-free for at least five years.&#xD;
&#xD;
          3. Previous exposure to brentuximab vedotin (BV).&#xD;
&#xD;
          4. History of allergic response to BV-CHEP or its components or to any of the required&#xD;
             prophylactic medications or reasonable alternatives.&#xD;
&#xD;
          5. Symptomatic cardiac disease including ventricular dysfunction, left ventricular&#xD;
             ejection fraction &lt; 40%, symptomatic coronary artery disease or symptomatic&#xD;
             arrhythmias&#xD;
&#xD;
          6. Subjects with severe hepatic insufficiency Child-Pugh Score &gt; 6&#xD;
&#xD;
          7. Subjects with severe renal impairment (i.e., creatinine clearance ≤ 30 mL/min; see&#xD;
             Appendix B - Renal Impairment Guidelines).&#xD;
&#xD;
          8. Exclude patients with pre-existing neuropathy grade 2 or higher.&#xD;
&#xD;
          9. Patients receiving prohibited medications listed in the patient handout provided in&#xD;
             11.4 Appendix D: Prohibited Medications or Those to be used with Caution (ie,&#xD;
             ketoconazole, itraconazole, ritonavir, macrolide antibiotics, erythromycin phenytoin,&#xD;
             phenobarbital, carbamazepine, and valproic acid).&#xD;
&#xD;
         10. Patients with a parenchymal brain lesion thought to be consistent with active lymphoma&#xD;
             on screening CT/MRI. Of note, patients with cerebrospinal fluid (CSF) involvement&#xD;
             alone are not excluded.&#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>Dittus Christopher, DO, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>UNC Lineberger Comprehensive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>South Broward/Memorial Healthcare System</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center (BIDMC)</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://unclineberger.org/research/</url>
    <description>University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Brentuximab Vedotin</keyword>
  <keyword>Adcetris</keyword>
  <keyword>Lymphoma</keyword>
  <keyword>Leukemia</keyword>
  <keyword>CD30</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>Leukemia, T-Cell</mesh_term>
    <mesh_term>Leukemia-Lymphoma, Adult T-Cell</mesh_term>
    <mesh_term>Lymphatic Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brentuximab Vedotin</mesh_term>
  </intervention_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/NCT03264131
org study id: LCCC1637
nct id: NCT03264131
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Adult T-cell leukemia/lymphoma (ATLL) is a rare form of cancer found mostly among people from
      the Caribbean islands, Western Africa, Brazil, Iran, and Japan. Most cases of this disease in
      the United States occur along the East Coast due to emigration from the Caribbean islands.
      There is currently no standard treatment for ATLL. Research shows that patients who go into
      first time remission (respond completely or partially to treatment) and have a bone marrow
      transplant have the best outcomes. Traditional chemotherapy treatments have generally not
      worked well in patients with ATLL. Additionally, not all patients will be eligible for a bone
      marrow transplant.

      The purpose of this study is to see how well individuals with ATLL respond to an
      investigational cancer treatment. This investigational treatment combines a drug called
      brentuximab vedotin with a standard chemotherapy treatment made up of cyclophosphamide,
      doxorubicin, etoposide, and prednisone. This treatment is considered investigational because
      it is not approved by the United States Food and Drug Administration (FDA) for the treatment
      of ATLL.

      Brentuximab vedotin, also known as Adcetris, is approved by the United States Food and Drug
      Administration (FDA) for treatment of certain types of lymphomas, including peripheral T-cell
      lymphomas when combined with cyclophosphamide, doxorubicin, and prednisone in patients whose
      cancer cells express a type of marker called CD30.

      Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it.
      Antibodies are proteins that are part of the immune system. They can stick to and attack
      specific targets on cancer cells. The antibody part of brentuximab vedotin sticks to a target
      called cluster of differentiation 30 (CD30) that is located on the outside of the cancer
      cells. Normal cells have little or no CD30 on their surface. ATLL cancer cells often have a
      larger amount of CD30 on their surface than normal cells. However, CD30 is found in different
      amounts on ATLL cancer cells. This study will also test the amount of CD30 found on each
      participant's cancer cells. Researchers will be looking to see if the response to the study
      treatment varies based on the amount of CD30 found on the outside participants' cancer cells.

      In another study, brentuximab vedotin was combined in another study with cyclophosphamide,
      doxorubicin, and prednisone. The study included patients with various types of T-cell
      lymphomas. Two of the patients enrolled in that study had ATLL. Both had a complete response
      (no evidence of disease). The researchers in this study (LCCC 1637) have added etoposide to
      the combination of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone.
      They predict that the addition of etoposide will improve patient outcomes. Research shows
      that etoposide helps improve outcomes in patients with certain types of T-cell lymphomas who
      undergo chemotherapy treatment. This investigational combination of brentuximab vedotin with
      cyclophosphamide, doxorubicin, etoposide, and prednisone is called BV-CHEP.
STUDY OBJECTIVES

      Primary Objective To define the proportion of subjects with CR after 4-6 cycles of
      brentuximab vedotin in combination with cyclophosphamide, doxorubicin, etoposide, and
      prednisone (BV-CHEP) in the treatment of adult T-cell leukemia/lymphoma.

      Secondary Objectives

      To estimate the overall response rate (ORR) with 4-6 cycles of BV-CHEP therapy in patients
      with adult T-cell leukemia/lymphoma.

      To determine progression-free survival (PFS) for BV-CHEP in patients with adult T-cell
      leukemia/lymphoma who received or did not receive BV maintenance.

      To determine duration of response to BV-CHEP in patients with adult T-cell leukemia/lymphoma
      who received or did not receive BV maintenance.

      To determine overall survival (OS) of patients with adult T-cell leukemia/lymphoma treated
      with BV-CHEP who received or did not receive BV maintenance therapy.

      To evaluate the toxicity and tolerability of BV-CHEP and BV maintenance therapy via the
      National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03).

      *Note: After completion or withdrawal from BV-CHEP therapy, patients will segregate into one
      of the following groups: 1) those who progressed on BV-CHEP; 2) those who completed 4-6
      cycles of BV-CHEP and went on to allogeneic transplant; 3) those who completed 6 cycles of
      BV-CHEP but were CD30 negative and ineligible for maintenance therapy; and 4) those who
      completed 6 cycles of BV-CHEP, were CD30 positive, but continued study treatment on BV in the
      maintenance phase of the study.

      ENDPOINTS

      Primary Endpoint

      Criteria for CR after 4-6 cycles of BV-CHEP will be based on the International Workshop to
      standardize response criteria for malignant lymphomas (ie, Lugano Criteria per Cheson, et al.
      J Clin Oncol. 2014;32(27):3059-68).

      Secondary Endpoints

      Criteria for overall response will be based on the International Workshop to standardize
      response criteria for malignant lymphomas (ie, Lugano Criteria per Cheson, et al. J Clin
      Oncol. 2014;32(27):3059-68).

      PFS is defined as time from D1 of treatment until disease progression (based on Lugano
      criteria) or death from any cause.

      Duration of response is defined as the time from documentation of tumor response per Lugano
      criteria to disease progression

      OS is defined as the time from D1 of treatment until death from any cause

      Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03

      TREATMENT INFORMATION

      Patients will undergo screening to see if they are eligible. If eligible, participants will
      start by receiving 2 cycles of BV-CHEP (cycles 1 and 2). After 2 cycles of BV-CHEP,
      participants will have a positron emission tomography/computed tomography (PET/CT) or a CT
      scan to assess their disease. If the scan shows the cancer has stayed the same or gotten
      better, participants may continue taking BV-CHEP for two more cycles (cycle 3 and 4). If, at
      any time during study treatment, a participant's disease gets worse, the participant will end
      study treatment and other treatment options will be discussed with you.

      If a participant continues on BV-CHEP, at the beginning of cycle 5, the participant will have
      a PET/CT scan. If the cancer has gotten better and the participant is eligible for a bone
      marrow transplant, he/she will have the transplant. If the participant is not eligible for a
      bone marrow transplant and the cancer has stayed the same or gotten better, the participant
      may continue on BV-CHEP for two more cycles (cycles 5 and 6).

      At the end of cycle 6 of BV-CHEP, participants will have another PET/CT scan. If the scan
      shows the cancer has gotten better and the participant is eligible for a bone marrow
      transplant, he/she will have the transplant. If a participant is not eligible for a bone
      marrow transplant and his/her cancer cells did not test positive for CD30, the participant
      will end study treatment. The study doctor will discuss other treatment options that are not
      part of this study with the participant.

      Participants may continue on brentuximab vedotin alone as maintenance therapy if:

        -  They are not eligible for a bone marrow transplant,

        -  Their cancer cells tested positive for CD30, and

        -  Their cancer has not gotten worse after taking BV-CHEP.

      Participants will be removed from BV maintenance therapy if their cancer get worse.

      DURATION OF THERAPY Therapy in LCCC 1637 involves up to 6 cycles of treatment with
      brentuximab vedotin (BV) with a chemotherapy treatment made up of cyclophosphamide,
      doxorubicin, etoposide, and prednisone (CHEP). Each cycle is 21 days long. Participants may
      continue on BV alone as maintenance therapy after 6 cycles of BV-CHEP if they meet the
      requirements outlined above. Each cycles of BV maintenance therapy is 21-day long. BV
      maintenance therapy may continue until a participant's disease progresses.

      DURATION OF FOLLOW-UP PERIOD Participants will be followed for survival for up to 5 years.
      They will also have a PET/CT or CT scan and a blood test every 6 months for 2 years after
      study treatment ends.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of subjects with Complete Response after 2-6 cycles of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP)
time frame: 18 weeks
description: Criteria for CR after 2-6 cycles of BV-CHEP will be based on the International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria).
measure: Overall response rate (ORR) associated with 2-6 cycles of BV-CHEP therapy in patients with adult T-Cell leukemia/lymphoma.
time frame: 70 weeks
description: ORR will be evaluated as the rate of complete responses (CR) + partial responses (PR) as defined by the International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria). Patients with leukemic component to their disease at baseline will be assessed per Adult T-Cell Leukemia/Lymphoma National Comprehensive Cancer Network (NCCN) guidelines version 2.2017
measure: Progression-free survival (PFS) for BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.
time frame: 5 years
description: PFS will be assessed from day 1 of treatment until disease progression (based on International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria) or death.
measure: Duration of response to BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.
time frame: 3 years
description: Duration of response is defined as the time from documentation of tumor response per Lugano criteria to disease progression. Subjects with a leukemic component to their disease at baseline will have peripheral blood assessed per adult T-cell leukemia/lymphoma NCCN Guidelines version 2.2017
measure: Overall survival (OS) of patients with adult T-cell leukemia/lymphoma treated with BV-CHEP who received or did not receive BV maintenance therapy.
time frame: 5 years
description: Overall survival is defined as the time from day 1 of treatment until death from any cause.
measure: Toxicity and tolerability of BV-CHEP and BV maintenance therapy via National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4)
time frame: 70 weeks
description: Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03, a scale from 1-mild to 5-death.
arm group label: Open-label, Multicenter, Single-Arm
arm group type: Experimental
description: This is a single-arm intervention where patients will receive concurrent therapy with BV+CHEP [(brentuximab vedotin; 1.8 mg/kg IV, on D1 every 21 days) (cyclophosphamide 750 mg/m^2 on D1; doxorubicin 50 mg/m^2 on D1, etoposide 100 mg/m^2 IV infusion on D1-3; prednisone 100 mg orally once daily on D1-5; cycle length every 21 days)] for 2 to 6 cycles of induction therapy. After 6 cycles of BV + CHEP, responders (CR, PR or SD) who are not eligible for BMT and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV, every 21 days) until disease progression, withdrawal due to toxicity or death.
intervention type: Drug
intervention name: Brentuximab Vedotin
description: Brentuximab Vedotin will be given at 1.8 mg/kg IV over approximately 30 minutes on D1 every 21 days for 2-6 cycles. Responders (CR, PR or SD) who are not eligible for bone marrow transplant (BMT) and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV for approximately 30 minutes, every 21 days).
arm group label: Open-label, Multicenter, Single-Arm
intervention type: Drug
intervention name: CHEP
description: Cyclophosphamide- 750 mg/m^2 IV over approximately 1 hour on D1 every 21 days for 2-6 cycles
Doxorubicin- 50 mg/m^2 IV over approximately 3-5 minutes on D1 every 21 days for 2-6 cycles.
Etoposide - 100 mg/m^2 IV over approximately 1 hour each day for 3 days every 21 days for 2-6 cycles.
Prednisone - 100 mg, orally once daily for 5 days every 21 days for 2-6 cycles.
arm group label: Open-label, Multicenter, Single-Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dittus Christopher, DO, MPH
role: Principal Investigator
affiliation: UNC Lineberger Comprehensive Cancer Center
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://unclineberger.org/research/
description: University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Leukemia, T-Cell
mesh term: Leukemia-Lymphoma, Adult T-Cell
mesh term: Lymphatic Diseases
mesh term: Brentuximab Vedotin