<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/NCT03755804</url>
  </required_header>
  <id_info>
    <org_study_id>cHOD17</org_study_id>
    <secondary_id>NCI-2018-02924</secondary_id>
    <nct_id>NCT03755804</nct_id>
  </id_info>
  <brief_title>Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17</brief_title>
  <official_title>Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Jude Children's Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Teva Pharmaceuticals USA</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Jude Children's Research Hospital</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>
      This is a phase II study using risk and response-adapted therapy for low, intermediate and&#xD;
      high risk classical Hodgkin lymphoma. Chemotherapy regimens will be based on risk group&#xD;
      assignment. Low-risk and intermediate- risk patients will be treated with bendamustine,&#xD;
      etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine, and&#xD;
      prednisone (BEABOVP) chemotherapy. High-risk patients will receive Adcetris® (brentuximab&#xD;
      vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) (AEPA) and cyclophosphamide,&#xD;
      Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC) (CAPDac) chemotherapy.&#xD;
      Residual node radiotherapy will be given at the end of all chemotherapy only to involved&#xD;
      nodes that do not have an adequate response (AR) after 2 cycles of therapy for all risk&#xD;
      groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES&#xD;
&#xD;
        -  To evaluate the efficacy (adequate response) after 2 cycles of BEABOVP (bendamustine&#xD;
           substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in&#xD;
           low-risk and intermediate-risk patients with classical Hodgkin lymphoma (cHL).&#xD;
&#xD;
        -  To estimate the event-free survival in high-risk patients with classical Hodgkin&#xD;
           lymphoma (cHL).&#xD;
&#xD;
      SECONDARY OBJECTIVES&#xD;
&#xD;
        -  To describe the acute hematologic and infectious toxicities of BEABOVP (bendamustine&#xD;
           substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in&#xD;
           patients with low-risk and intermediate- risk cHL as they relate to transfusion&#xD;
           requirements, hematopoietic growth factor support, episodes of febrile neutropenia and&#xD;
           hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events&#xD;
           (CTCAE), version 5.0.&#xD;
&#xD;
        -  To describe the acute hematologic, neuropathic, and infectious toxicities of AEPA/CAPDac&#xD;
           in patients with high-risk cHL as they relate to transfusion requirements, hematopoietic&#xD;
           growth factor support, episodes of grade 3 and 4 sensory or motor neuropathy, episodes&#xD;
           of febrile neutropenia and hospitalizations, according to the NCI Common Terminology&#xD;
           Criteria for Adverse Events (CTCAE), version 5.0.&#xD;
&#xD;
        -  To evaluate patterns of failure in irradiated and non-irradiated patients.&#xD;
&#xD;
        -  To estimate the EFS functions of LR and IR patients, and compare with those in&#xD;
           previously published studies.&#xD;
&#xD;
        -  To estimate the response rate in HR patients and compare with historical and literature&#xD;
           rates.&#xD;
&#xD;
        -  To compare response rates in LR and IR patients with historical and literature rates.&#xD;
&#xD;
        -  To compare the EFS function of HR patients with that in previously published studies.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES&#xD;
&#xD;
        -  To evaluate the plasma pharmacokinetics of bendamustine along with predictors of its&#xD;
           variability when used as part of BEABOVP regimen for pediatric cHL patients&#xD;
&#xD;
        -  To explore the patterns and dynamics of T-cell clonality in classical Hodgkin lymphoma&#xD;
&#xD;
        -  To explore the association between TARC, total metabolic tumor volume, stage, risk group&#xD;
           and treatment response.&#xD;
&#xD;
        -  To establish next generation sequencing of ctDNA as a reliable method of non-invasively&#xD;
           profiling tumor-associated mutations in pediatric patients with HL.&#xD;
&#xD;
        -  To determine if kinetics of ctDNA in patients with pediatric HL during treatment are&#xD;
           predictive of outcome.&#xD;
&#xD;
        -  To obtain baseline testing by St. Jude Lifetime Study (SJLIFE) to allow for enhanced&#xD;
           survivorship follow-up:&#xD;
&#xD;
             -  Neurologic testing&#xD;
&#xD;
             -  Neurocognitive testing&#xD;
&#xD;
             -  Quantitative brain imaging&#xD;
&#xD;
             -  Polysomnography&#xD;
&#xD;
             -  Cardiovascular testing (valvular testing, arterial elasticity, carotid-femoral&#xD;
                pulse wave velocity, orthostatic hypotension, heart rate variability&#xD;
&#xD;
             -  Neuropathy screening&#xD;
&#xD;
             -  Changes in body mass index composition during therapy&#xD;
&#xD;
      Low-risk and Intermediate-risk: Low-risk patients will receive 2 cycles of BEABOVP and&#xD;
      Intermediate-risk patients will receive 3 cycles of BEABOVP.&#xD;
&#xD;
      BEABOVP regimen: Patients will receive bendamustine day 1, etoposide day 15, Adriamycin®&#xD;
      (doxorubicin) days 1 and 15, bleomycin days 8 and 22, Oncovin® (vincristine) days 8 and 22,&#xD;
      vinblastine days 1 and 15, and prednisone two or three times per day every other day of each&#xD;
      cycle for a total of 14 days of steroids.&#xD;
&#xD;
      High-risk patients will receive 2 cycles of AEPA and 4 cycles of CAPDac.&#xD;
&#xD;
      AEPA regimen: Patients will receive Adcedris® (brentuximab vedotin) days 1, 8 and 15,&#xD;
      etoposide days 1 to 5, prednisone two or three times daily days 1 to 15 and Adriamycin®&#xD;
      (doxorubicin) days 1 and 15.&#xD;
&#xD;
      CAPDac regimen: Patients will receive cyclophosphamide days 1 and 8, Adcetris® (brentuximab&#xD;
      vedotin) days 1 and 8, prednisone two or three times daily days 1 to 15 and Dacarbazine®&#xD;
      (DTIC) days 1 to 3.&#xD;
&#xD;
      Residual node radiotherapy will be given at the end of all chemotherapy only to involved&#xD;
      nodes that do not have an AR after 2 cycles of therapy for all risk groups.&#xD;
&#xD;
      Steroids will be omitted after 2 cycles for any IR or HR patient with an AR after 2 cycles of&#xD;
      therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 12, 2018</start_date>
  <completion_date type="Anticipated">July 1, 2028</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2027</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate of adequate response</measure>
    <time_frame>after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment</time_frame>
    <description>The 70 evaluable low-risk patients enrolled will be evaluated for this objective.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response rate of adequate response</measure>
    <time_frame>after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment</time_frame>
    <description>The 65 evaluable intermediate-risk patients enrolled will be evaluated for this objective</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment</time_frame>
    <description>Time to event defined as relapse, progression or death. The 115 evaluable high-risk patients participants enrolled will be evaluated for this objective.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events in low-risk and intermediate-risk patients</measure>
    <time_frame>From enrollment to end of therapy (approximately 8 months</time_frame>
    <description>According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events in high-risk patients</measure>
    <time_frame>From enrollment to end of therapy (approximately 8 months</time_frame>
    <description>According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local failure rate</measure>
    <time_frame>From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment</time_frame>
    <description>Local failure rate in irradiated and non-irradiated patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment</time_frame>
    <description>Time to event defined as relapse, progression or death. The EFS for the low-risk patients and intermediate-risk patients are compared to those in HOD08 and HOD05, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment</time_frame>
    <description>Response rate of adequate response after 2 cycles of AEPA in the high-risk patients with FDG-PET compared to that after 2 cycles of AEPA in HLHR13.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment</time_frame>
    <description>Response rate of adequate response after 2 cycles of BEABOVP in the low-risk and high-risk patients with FDG-PET compared to those after 2 cycles of STANFORD V chemotherapy in HOD08 and HOD05, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment</time_frame>
    <description>Time to event defined as relapse, progression or death. The EFS for the high-risk patients is compared to those in HLHR13.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Low-Risk</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive 2 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive 3 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High-Risk</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive 2 cycles of AEPA: Adcedris® (brentuximab vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) and 4 cycles of CAPDac: cyclophosphamide, Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC). For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bendamustine</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>TREANDA (R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>High-Risk</arm_group_label>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>VP-16</other_name>
    <other_name>Vepeside</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>High-Risk</arm_group_label>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>Adriamycin (R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bleomycin</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>Blenoxane (R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>Oncovin (R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vinblastine</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>Velban (R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Given orally (PO)</description>
    <arm_group_label>High-Risk</arm_group_label>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>Prednisolone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Filgrastim</intervention_name>
    <description>Given subcutaneously (SQ) or IV</description>
    <arm_group_label>High-Risk</arm_group_label>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>Neupogen (R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>High-Risk</arm_group_label>
    <other_name>Adcetris</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>High-Risk</arm_group_label>
    <other_name>Cytoxan (R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DTIC</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>High-Risk</arm_group_label>
    <other_name>DACARBAZINE (R)</other_name>
    <other_name>Dimethyl Triazeno Imidazole Carboximide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality of Life Measurements</intervention_name>
    <description>Quality of Life measurements may be done in low-risk cycles 1 and 2 BEABOVP, intermediate-risk cycles 1, 2 and 3 BEABOVP and high-risk cycles 1 and 2 AEPA and cycles 1, 2, 3, and 4 CAPDac. QOL may be done at year 1, 2 and 5 for all risk groups.</description>
    <arm_group_label>High-Risk</arm_group_label>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>Quality of Life Measurements (QOL)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy</intervention_name>
    <description>Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy for all risk groups. Radiotherapy will be administered after completion of all chemotherapy upon hematologic count recovery.</description>
    <arm_group_label>High-Risk</arm_group_label>
    <arm_group_label>Intermediate-Risk</arm_group_label>
    <arm_group_label>Low-Risk</arm_group_label>
    <other_name>radiation therapy</other_name>
    <other_name>irradiation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed, previously untreated CD30+ classical HL. (Participants are&#xD;
             still eligible if they received limited emergent RT or steroid therapy - maximum of 7&#xD;
             days if within the last month or as approved by PI).&#xD;
&#xD;
          -  Age ≤ 21 years at the time of diagnosis (i.e., participants are eligible until their&#xD;
             22nd birthday) for low-risk and intermediate-risk&#xD;
&#xD;
          -  Age ≤ 25 years at the time of diagnosis (i.e., participants are eligible until their&#xD;
             26th birthday) for high-risk&#xD;
&#xD;
          -  All Ann Arbor stages.&#xD;
&#xD;
               -  Low-Risk: IA, IIA (excluding patients with &quot;E&quot; lesions or mediastinal bulk)&#xD;
&#xD;
               -  Intermediate-Risk: IA or IIA with &quot;E&quot; lesions or bulky mediastinal adenopathy&#xD;
                  (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph)&#xD;
                  and IB, IIIA.&#xD;
&#xD;
               -  High-Risk: IIB, IIIB, IV&#xD;
&#xD;
          -  Adequate renal function based on GFR ≥ 70 ml/min/1.73m2 OR serum creatinine adjusted&#xD;
             for age and gender as follows: Age 1 to &lt; 2 years: maximum serum creatinine 0.6 mg/dL&#xD;
             for males and 0.6 mg/dL for females, Age 2 to &lt; 6 years: maximum serum creatinine 0.8&#xD;
             mg/dL for males and 0.8 mg/dL for females, Age 6 to &lt; 10 years: maximum serum&#xD;
             creatinine 1 mg/dL for males and 1 mg/dL for females, Age 10 to &lt; 13 years: maximum&#xD;
             serum creatinine 1.2 mg/dL for males and 1.2 mg/dL for females, Age 13 to &lt; 16 years:&#xD;
             maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females, Age ≥16 years:&#xD;
             maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females&#xD;
&#xD;
          -  Adequate hepatic function (total bilirubin ≤ 1.5 x ULN for age, and AST/ALT ≤ 2.5 x&#xD;
             ULN for age).&#xD;
&#xD;
          -  Adequate hematologic criteria at baseline, unless secondary to Hodgkin disease&#xD;
             diagnosis&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥1000/µL&#xD;
&#xD;
               -  Platelets ≥ 75,000/µL&#xD;
&#xD;
          -  Adequate cardiac function defined as shortening fraction of ≥ 27% by echocardiogram or&#xD;
             MUGA, unless decreased function is due to large mediastinal mass or effusion related&#xD;
             to HL.&#xD;
&#xD;
          -  Adequate pulmonary function defined as no evidence of dyspnea at rest, no exercise&#xD;
             intolerance, and a pulse oximetry &gt; 92% on room air unless secondary to a large&#xD;
             mediastinal mass or effusion related to HL.&#xD;
&#xD;
          -  Female participant who is post-menarchal must have a negative urine or serum pregnancy&#xD;
             test.&#xD;
&#xD;
          -  Female or male participant of reproductive potential must agree to use an effective&#xD;
             contraceptive method throughout duration of study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  CD30 negative HL.&#xD;
&#xD;
          -  Has received prior therapy for Hodgkin lymphoma&#xD;
&#xD;
          -  Inadequate organ function&#xD;
&#xD;
          -  High-risk participants with a history of ≥ grade 2 peripheral neuropathy or any active&#xD;
             neurologic disease that would impede the ability to assess neurologic toxicities.&#xD;
&#xD;
          -  Inability or unwillingness of research participant or legal guardian / representative&#xD;
             to give written informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jamie Flerlage, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jamie Flerlage, MD,MS</last_name>
    <phone>866-278-5833</phone>
    <email>referralinfo@stjude.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Lucile Packard Children's Hospital Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Link, MD</last_name>
      <phone>650-495-8815</phone>
      <email>mlink@stanford.edu</email>
    </contact>
    <investigator>
      <last_name>Michael Link, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St. Jude Midwest Affiliate - Peoria</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pedro De Alarcon, MD</last_name>
      <phone>888-226-4343</phone>
      <email>pdealarc@uic.edu</email>
    </contact>
    <investigator>
      <last_name>Pedro De Alarcon, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St. Jude Affiliate Baton Rouge Clinic (Our Lady of the Lakes Regional Medical Center)</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeffrey Deyo, MD, PhD</last_name>
      <phone>225-374-1485</phone>
      <email>jeff.deyo@stjude.org</email>
    </contact>
    <investigator>
      <last_name>Jeffrey Deyo, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Maine Children's Cancer Program</name>
      <address>
        <city>Scarborough</city>
        <state>Maine</state>
        <zip>04074</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eric Larsen, MD</last_name>
      <phone>207-885-7565</phone>
      <email>larsee1@mmc.org</email>
    </contact>
    <investigator>
      <last_name>Eric Larsen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alison M. Friedman, MD</last_name>
      <phone>617-726-2737</phone>
      <email>afriedmann@partners.org</email>
    </contact>
    <investigator>
      <last_name>Alison M. Friedman, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Angela M. Feraco, MD, MMSc</last_name>
      <phone>617-632-5508</phone>
      <email>Angela_Feraco@dfci.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Angela M. Feraco, MD, MMSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St. Jude Affiliate Clinic at Novant Health Hemby Children's Hospital</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christine Bolen, MD</last_name>
      <phone>704-384-1900</phone>
      <email>cybolen@novanthealth.org</email>
    </contact>
    <investigator>
      <last_name>Christine Bolen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jamie Flerlage, MD, MS</last_name>
      <phone>866-278-5833</phone>
      <email>referralinfo@stjude.org</email>
    </contact>
    <investigator>
      <last_name>Jamie Flerlage, MD, MS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.stjude.org</url>
    <description>St. Jude Children's Research Hospital</description>
  </link>
  <link>
    <url>http://www.stjude.org/protocols</url>
    <description>ClinicalTrials Open at St. Jude</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hodgkin Lymphoma</keyword>
  <keyword>Pediatric Cancer</keyword>
  <keyword>Frontline Therapy</keyword>
  <keyword>Response Adapted Therapy</keyword>
  <keyword>Risk Adapted Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Bendamustine Hydrochloride</mesh_term>
    <mesh_term>Dacarbazine</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Bleomycin</mesh_term>
    <mesh_term>Brentuximab Vedotin</mesh_term>
    <mesh_term>Vinblastine</mesh_term>
    <mesh_term>Imidazole</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/NCT03755804
org study id: cHOD17
secondary id: NCI-2018-02924
nct id: NCT03755804
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase II study using risk and response-adapted therapy for low, intermediate and
      high risk classical Hodgkin lymphoma. Chemotherapy regimens will be based on risk group
      assignment. Low-risk and intermediate- risk patients will be treated with bendamustine,
      etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine, and
      prednisone (BEABOVP) chemotherapy. High-risk patients will receive Adcetris® (brentuximab
      vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) (AEPA) and cyclophosphamide,
      Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC) (CAPDac) chemotherapy.
      Residual node radiotherapy will be given at the end of all chemotherapy only to involved
      nodes that do not have an adequate response (AR) after 2 cycles of therapy for all risk
      groups.
PRIMARY OBJECTIVES

        -  To evaluate the efficacy (adequate response) after 2 cycles of BEABOVP (bendamustine
           substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in
           low-risk and intermediate-risk patients with classical Hodgkin lymphoma (cHL).

        -  To estimate the event-free survival in high-risk patients with classical Hodgkin
           lymphoma (cHL).

      SECONDARY OBJECTIVES

        -  To describe the acute hematologic and infectious toxicities of BEABOVP (bendamustine
           substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in
           patients with low-risk and intermediate- risk cHL as they relate to transfusion
           requirements, hematopoietic growth factor support, episodes of febrile neutropenia and
           hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events
           (CTCAE), version 5.0.

        -  To describe the acute hematologic, neuropathic, and infectious toxicities of AEPA/CAPDac
           in patients with high-risk cHL as they relate to transfusion requirements, hematopoietic
           growth factor support, episodes of grade 3 and 4 sensory or motor neuropathy, episodes
           of febrile neutropenia and hospitalizations, according to the NCI Common Terminology
           Criteria for Adverse Events (CTCAE), version 5.0.

        -  To evaluate patterns of failure in irradiated and non-irradiated patients.

        -  To estimate the EFS functions of LR and IR patients, and compare with those in
           previously published studies.

        -  To estimate the response rate in HR patients and compare with historical and literature
           rates.

        -  To compare response rates in LR and IR patients with historical and literature rates.

        -  To compare the EFS function of HR patients with that in previously published studies.

      EXPLORATORY OBJECTIVES

        -  To evaluate the plasma pharmacokinetics of bendamustine along with predictors of its
           variability when used as part of BEABOVP regimen for pediatric cHL patients

        -  To explore the patterns and dynamics of T-cell clonality in classical Hodgkin lymphoma

        -  To explore the association between TARC, total metabolic tumor volume, stage, risk group
           and treatment response.

        -  To establish next generation sequencing of ctDNA as a reliable method of non-invasively
           profiling tumor-associated mutations in pediatric patients with HL.

        -  To determine if kinetics of ctDNA in patients with pediatric HL during treatment are
           predictive of outcome.

        -  To obtain baseline testing by St. Jude Lifetime Study (SJLIFE) to allow for enhanced
           survivorship follow-up:

             -  Neurologic testing

             -  Neurocognitive testing

             -  Quantitative brain imaging

             -  Polysomnography

             -  Cardiovascular testing (valvular testing, arterial elasticity, carotid-femoral
                pulse wave velocity, orthostatic hypotension, heart rate variability

             -  Neuropathy screening

             -  Changes in body mass index composition during therapy

      Low-risk and Intermediate-risk: Low-risk patients will receive 2 cycles of BEABOVP and
      Intermediate-risk patients will receive 3 cycles of BEABOVP.

      BEABOVP regimen: Patients will receive bendamustine day 1, etoposide day 15, Adriamycin®
      (doxorubicin) days 1 and 15, bleomycin days 8 and 22, Oncovin® (vincristine) days 8 and 22,
      vinblastine days 1 and 15, and prednisone two or three times per day every other day of each
      cycle for a total of 14 days of steroids.

      High-risk patients will receive 2 cycles of AEPA and 4 cycles of CAPDac.

      AEPA regimen: Patients will receive Adcedris® (brentuximab vedotin) days 1, 8 and 15,
      etoposide days 1 to 5, prednisone two or three times daily days 1 to 15 and Adriamycin®
      (doxorubicin) days 1 and 15.

      CAPDac regimen: Patients will receive cyclophosphamide days 1 and 8, Adcetris® (brentuximab
      vedotin) days 1 and 8, prednisone two or three times daily days 1 to 15 and Dacarbazine®
      (DTIC) days 1 to 3.

      Residual node radiotherapy will be given at the end of all chemotherapy only to involved
      nodes that do not have an AR after 2 cycles of therapy for all risk groups.

      Steroids will be omitted after 2 cycles for any IR or HR patient with an AR after 2 cycles of
      therapy.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate of adequate response
time frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment
description: The 70 evaluable low-risk patients enrolled will be evaluated for this objective.
measure: Response rate of adequate response
time frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment
description: The 65 evaluable intermediate-risk patients enrolled will be evaluated for this objective
measure: Event-free survival
time frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment
description: Time to event defined as relapse, progression or death. The 115 evaluable high-risk patients participants enrolled will be evaluated for this objective.
measure: Number of adverse events in low-risk and intermediate-risk patients
time frame: From enrollment to end of therapy (approximately 8 months
description: According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
measure: Number of adverse events in high-risk patients
time frame: From enrollment to end of therapy (approximately 8 months
description: According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
measure: Local failure rate
time frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment
description: Local failure rate in irradiated and non-irradiated patients
measure: Event-free survival
time frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment
description: Time to event defined as relapse, progression or death. The EFS for the low-risk patients and intermediate-risk patients are compared to those in HOD08 and HOD05, respectively.
measure: Response rate
time frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment
description: Response rate of adequate response after 2 cycles of AEPA in the high-risk patients with FDG-PET compared to that after 2 cycles of AEPA in HLHR13.
measure: Response rate
time frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment
description: Response rate of adequate response after 2 cycles of BEABOVP in the low-risk and high-risk patients with FDG-PET compared to those after 2 cycles of STANFORD V chemotherapy in HOD08 and HOD05, respectively.
measure: Event-free survival
time frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment
description: Time to event defined as relapse, progression or death. The EFS for the high-risk patients is compared to those in HLHR13.
arm group label: Low-Risk
arm group type: Experimental
description: Participants receive 2 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.
arm group label: Intermediate-Risk
arm group type: Experimental
description: Participants receive 3 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.
arm group label: High-Risk
arm group type: Experimental
description: Participants receive 2 cycles of AEPA: Adcedris® (brentuximab vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) and 4 cycles of CAPDac: cyclophosphamide, Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC). For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.
intervention type: Drug
intervention name: bendamustine
description: Given intravenously (IV)
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: TREANDA (R)
intervention type: Drug
intervention name: Etoposide
description: Given intravenously (IV)
arm group label: High-Risk
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: VP-16
other name: Vepeside
intervention type: Drug
intervention name: Doxorubicin
description: Given intravenously (IV)
arm group label: High-Risk
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: Adriamycin (R)
intervention type: Drug
intervention name: Bleomycin
description: Given intravenously (IV)
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: Blenoxane (R)
intervention type: Drug
intervention name: Vincristine
description: Given intravenously (IV)
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: Oncovin (R)
intervention type: Drug
intervention name: Vinblastine
description: Given intravenously (IV)
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: Velban (R)
intervention type: Drug
intervention name: Prednisone
description: Given orally (PO)
arm group label: High-Risk
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: Prednisolone
intervention type: Drug
intervention name: Filgrastim
description: Given subcutaneously (SQ) or IV
arm group label: High-Risk
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: Neupogen (R)
intervention type: Drug
intervention name: Brentuximab Vedotin
description: Given intravenously (IV)
arm group label: High-Risk
other name: Adcetris
intervention type: Drug
intervention name: Cyclophosphamide
description: Given intravenously (IV)
arm group label: High-Risk
other name: Cytoxan (R)
intervention type: Drug
intervention name: DTIC
description: Given intravenously (IV)
arm group label: High-Risk
other name: DACARBAZINE (R)
other name: Dimethyl Triazeno Imidazole Carboximide
intervention type: Other
intervention name: Quality of Life Measurements
description: Quality of Life measurements may be done in low-risk cycles 1 and 2 BEABOVP, intermediate-risk cycles 1, 2 and 3 BEABOVP and high-risk cycles 1 and 2 AEPA and cycles 1, 2, 3, and 4 CAPDac. QOL may be done at year 1, 2 and 5 for all risk groups.
arm group label: High-Risk
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: Quality of Life Measurements (QOL)
intervention type: Radiation
intervention name: Radiotherapy
description: Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy for all risk groups. Radiotherapy will be administered after completion of all chemotherapy upon hematologic count recovery.
arm group label: High-Risk
arm group label: Intermediate-Risk
arm group label: Low-Risk
other name: radiation therapy
other name: irradiation
criteria: 
gender: All
minimum age: N/A
maximum age: 25 Years
healthy volunteers: No
last name: Jamie Flerlage, MD, MS
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
last name: Jamie Flerlage, MD,MS
phone: 866-278-5833
email: referralinfo@stjude.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.stjude.org
description: St. Jude Children's Research Hospital
url: http://www.stjude.org/protocols
description: ClinicalTrials Open at St. Jude
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Prednisone
mesh term: Prednisolone
mesh term: Cyclophosphamide
mesh term: Bendamustine Hydrochloride
mesh term: Dacarbazine
mesh term: Doxorubicin
mesh term: Etoposide
mesh term: Vincristine
mesh term: Bleomycin
mesh term: Brentuximab Vedotin
mesh term: Vinblastine
mesh term: Imidazole