<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/NCT02243436</url>
  </required_header>
  <id_info>
    <org_study_id>BRESHAP-GELTAMO.LH-2013</org_study_id>
    <secondary_id>2014-000835-17</secondary_id>
    <nct_id>NCT02243436</nct_id>
  </id_info>
  <brief_title>Brentuximab Vedotin in Pre-transplant Induction and Consolidation for Relapsed or Refractory Hodgkin Lymphoma</brief_title>
  <official_title>Phase I-II Clinical Trial for the Evaluation of Brentuximab Vedotin Plus Etoposide, Solumoderin (Methylprednisolone), High Dose ARA-C (Cytarabine) and Cisplatin in the Transplant and Post-transplant Management for Relapsed or Refractory Classical Hodgkin Lymphoma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase I trial aimed to determine the Maximum Tolerable Dose of the BV in combination with&#xD;
      ESHAP in relapsed/resistant Hodgkin Lymphona patients and to evaluate response to treatment&#xD;
      with BV-ESHAP as salvage regimen prior to autologous stem cell transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Most patients suffering from Hodgkin's lymphoma (HL) can be successfully treated with&#xD;
      standard chemo- and/or radiotherapy. However, in patients with refractory disease/relapsing&#xD;
      after first line of therapy, conventional-dose chemotherapy regimens induce low remission&#xD;
      rates, with long-term disease free survival not higher than 10% of patients.&#xD;
&#xD;
      High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the&#xD;
      standard treatment for these patients. This treatment approach results in long-term&#xD;
      remissions in approximately 40-50% of relapsed patients, and in up to 25-30% of those with&#xD;
      primary refractory disease. The possibility of a cure depends on several prognostic factors,&#xD;
      however, in almost all series, the strongest prognostic factor has been the disease status&#xD;
      before ASCT. Patients with HL who do not achieve complete remission (CR) after induction&#xD;
      chemotherapy and those with unresponsive relapse have a very poor prognosis. Therefore, the&#xD;
      choice of a very active pre-transplant salvage chemotherapy regimen is extremely important to&#xD;
      improve results after ASCT. In addition, this activity should also be combined with a good&#xD;
      stem cell mobilizing potential and low toxicity profiled.&#xD;
&#xD;
      Several pre-transplant salvage regimens for refractory/relapsed HL are currently used with an&#xD;
      overall response (OR) and CR rates ranging from 60% to 88% and from 17% to 49%, respectively.&#xD;
      No randomized trial exists comparing the effectiveness of these regimens. ESHAP (Etoposide,&#xD;
      Solumoderin (methylprednisolone), Ara-C (Cytarabine) and cisplatin) is one of the most&#xD;
      commonly used regimens. ESHAP induces an OR and CR of 73% and 41%, respectively, with 5%&#xD;
      toxic deaths. In the present study, a combination of ESHAP plus Brentuximab Vedotin (BV) is&#xD;
      proposed as pre-transplant therapy with the aim to improve the CR rate before ASCT.&#xD;
&#xD;
      HL is characterized by the presence of CD30-positive Hodgkin Reed-Sternberg cells. The&#xD;
      antibody-drug conjugate BV delivers the highly potent antimicrotubule agent monomethyl&#xD;
      auristatin E (MMAE) to CD30-positive malignant cells by binding specifically to CD30 on the&#xD;
      cell surface and releasing MMAE inside the cell via lysosomal degradation.&#xD;
&#xD;
      Binding of MMAE to tubulin results in apoptotic death of the CD30 expressing tumor cell.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 11, 2014</start_date>
  <completion_date type="Actual">January 14, 2019</completion_date>
  <primary_completion_date type="Actual">January 2019</primary_completion_date>
  <phase>Phase 1/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>Recommended dose</measure>
    <time_frame>Day 21 of cycle 1 (3 weeks after start of treatment)</time_frame>
    <description>During phase I, defined as the maximum Tolerable Dose of the BV in combination with ESHAP in relapsed/resistant HL patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Global response rate prior to ASCT</measure>
    <time_frame>9 weeks (after start of treatment)</time_frame>
    <description>During phase II, Global response rate after BV-ESHAP as salvage regimen prior to ASCT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete response</measure>
    <time_frame>9 weeks (after start of treatment)</time_frame>
    <description>Percentage of patients with complete response rate after BV-ESHAP as salvage regimen prior to ASCT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity according to the CTC criteria</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
    <description>To determine the toxicity of BV-ESHAP regimen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stem cell mobilization capacity</measure>
    <time_frame>After first or second cycle of treatment</time_frame>
    <description>To assess the stem cell mobilization capacity of the BV-ESHAP regimen: determine the expanse and effectiveness of the extraction of stem cells from peripheral blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transplant-related mortality (TRM)</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
    <description>Percentage of patients alive after first dose of treatment through follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
    <description>Percentage of patients without progression of disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-Free Survival</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
    <description>Percentage of patients without event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to HL Progression</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-Free Survival</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Duration</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
    <description>Length of time between date of evidenced response and progression of disease or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lymphoma-Specific Survival</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Next Treatment</measure>
    <time_frame>Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>CLASSICAL HODGKIN LYMPHOMA</condition>
  <arm_group>
    <arm_group_label>BV-ESHAP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>- 3 cycles every 21 days:&#xD;
Brentuximab Vedotin, on day 1 (BV will be administered at three different doses 0.9mg/kg, 1.2mg/kg, 1.8mg/kg)&#xD;
Etoposide 40 mg/m2/day, on days 1 to 4&#xD;
Soludomerin (methylprednisolone) 250 mg/day, on days 1 to 4&#xD;
Cisplatin 25 mg/m2/day, on days 1 to 4&#xD;
Ara C (cytarabine) 2 g/m2, on day 5&#xD;
- A fourth dose of BV will be given 21 days after the third BV dose during the evaluation of response before the transplant.&#xD;
- Autologous peripheral blood stem cell transplant&#xD;
- A fifth dose of BV (1.8mg/kg) will be given on between day 28 and 35 post-transplant, followed by two additional doses (1.8mg/kg) every 3 weeks, to complete a total of 7 BV infusions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin</intervention_name>
    <description>Brentuximab Vedotin, 0.9mg/kg, 1.2mg/kg, 1.8mg/kg, day 1</description>
    <arm_group_label>BV-ESHAP</arm_group_label>
    <other_name>ADCETRIS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Intravenose use, 40mg/m2/day, on days 1 to 4</description>
    <arm_group_label>BV-ESHAP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Soludomerin</intervention_name>
    <description>Intravenous use, 250mg/day, on days 1 to 4</description>
    <arm_group_label>BV-ESHAP</arm_group_label>
    <other_name>Methylprednisolone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Intravenous use, 25mg/m2/day, on days 1 to 4</description>
    <arm_group_label>BV-ESHAP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ara C</intervention_name>
    <description>Intravenous use, 2g/m2, day 5</description>
    <arm_group_label>BV-ESHAP</arm_group_label>
    <other_name>Cytarabine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must have fully recovered from the acute toxic effects of all prior chemotherapy,&#xD;
        immunotherapy, or radiotherapy prior to entering this study&#xD;
&#xD;
          -  Histologically confirmed relapsed or refractory classical HL after first line&#xD;
             chemotherapy. CD30 has to be positive&#xD;
&#xD;
          -  Age 18 to 65 years. Patient &gt;65 years old with ECOG ≤1 and absence of comorbidities&#xD;
             will be included in the study&#xD;
&#xD;
          -  ECOG ≤2&#xD;
&#xD;
          -  Karnofsky performance status ≥ 60&#xD;
&#xD;
          -  No major organ dysfunction&#xD;
&#xD;
          -  Biopsy at HL relapse or when refractoriness disease is diagnosed must be done prior to&#xD;
             BV-ESHAP. If biopsy cannot be performed, tumor biopsy at initial diagnosis of HL must&#xD;
             be available to be revised&#xD;
&#xD;
          -  Absence of prior history of other malignant diseases, except:&#xD;
&#xD;
        Basal cell carcinoma of the skin or uterine &quot;in situ&quot; carcinoma adequately treated Any&#xD;
        curable neoplasia adequately treated that has achieved complete response and has remained&#xD;
        in such status longer than 3 years&#xD;
&#xD;
          -  Female patient is either post-menopausal for at least 1 year before the screening&#xD;
             visit or surgically sterile or if of childbearing potential, agree to practice 2&#xD;
             effective methods of contraception, at the same time, from the time of signing the&#xD;
             informed consent through 30 days after the last dose of study drug, or agrees to&#xD;
             completely abstain from heterosexual intercourse&#xD;
&#xD;
          -  Male patients, even if surgically sterilized, agree to practice effective barrier&#xD;
             contraception during the entire study period and through 6 months after the last dose&#xD;
             of study drug, or agrees to completely abstain from heterosexual intercourse&#xD;
&#xD;
          -  Life-expectancy &gt;3 months&#xD;
&#xD;
          -  Platelet count ≥75•109/L (or 20 if due to Bone Marrow [BM] infiltration) absolute&#xD;
             neutrophil count ≥1.5•109/L (or 0.5 if due to BM infiltration), and hemoglobin ≥ 8g/dL&#xD;
&#xD;
          -  Total Bilirubin: &lt;1.5 x UNL, unless clearly related to the disease (Gilbert disease&#xD;
             will be ruled out from this point)&#xD;
&#xD;
          -  AST and ALT: &lt;3 xUNL except liver infiltration&#xD;
&#xD;
          -  Serum creatinine: &lt; 2.0 mg/dL and/or creatinine clearance or calculated creatinine&#xD;
             clearance &gt; 40 mL/minute&#xD;
&#xD;
          -  Serum sodium &gt;130 mmol/L&#xD;
&#xD;
          -  Voluntary written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current active hepatic or biliary disease (with exception of patients with Gilbert's&#xD;
             syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease&#xD;
             per investigator assessment)&#xD;
&#xD;
          -  Serious medical or psychiatric illness likely to interfere with participation in this&#xD;
             clinical study&#xD;
&#xD;
          -  Patients that have been treated previously with anti-CD30 monoclonal antibodies&#xD;
&#xD;
          -  Myocardial infarction within 6 months prior to enrollment. Heart failure NYHA Class&#xD;
             III-IV, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence&#xD;
             of acute ischemia or active conduction system abnormalities. Recent evidence (within 6&#xD;
             months) of a left-ventricular ejection fraction &lt;50%&#xD;
&#xD;
          -  Peripheral neuropathy or neuropathic pain grade ≥ 2&#xD;
&#xD;
          -  Known cerebral or meningeal disease, including signs or symptoms of PML&#xD;
&#xD;
          -  Symptomatic neurologic disease compromising normal activities of daily living or&#xD;
             requiring medication&#xD;
&#xD;
          -  Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient&#xD;
             contained in brentuximab vedotin&#xD;
&#xD;
          -  Pregnant women or in breast-feeding period, or adults in childbearing period not using&#xD;
             an effective contraception method&#xD;
&#xD;
          -  Treatment with any known non-marketed drug substance or experimental therapy within&#xD;
             the longer of 5 terminal half-lives or 4 weeks prior to enrollment or currently&#xD;
             participating in any other interventional clinical study&#xD;
&#xD;
          -  Chronic or current infectious disease requiring systemic antibiotics, antifungal, or&#xD;
             antiviral treatment within two weeks prior to first study drug dose&#xD;
&#xD;
          -  History of significant cerebrovascular disease in the past 6 months or ongoing event&#xD;
             with active symptoms or sequelae&#xD;
&#xD;
          -  HIV positive&#xD;
&#xD;
          -  Significant concurrent, uncontrolled medical condition which may represent a risk for&#xD;
             the patient&#xD;
&#xD;
          -  Positive serology for HBV&#xD;
&#xD;
          -  Positive serology for HCV&#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>Ramón García-Sanz, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Salamanca</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitario Central de Asturias</name>
      <address>
        <city>Oviedo</city>
        <state>Asturias</state>
        <zip>33006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Català d'Oncologia, Hospital Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Català d'Oncologia, Hospital Duran i Reynals</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Son Espases</name>
      <address>
        <city>Palma</city>
        <state>Islas Baleares</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic i Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañon</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Canarias</name>
      <address>
        <city>Santa Cruz de Tenerife</city>
        <zip>38320</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2014</study_first_posted>
  <last_update_submitted>April 23, 2019</last_update_submitted>
  <last_update_submitted_qc>April 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CLASSICAL HODGKIN LYMPHOMA</keyword>
  <keyword>HODGKIN LYMPHOMA</keyword>
  <keyword>LYMPHOMA</keyword>
  <keyword>HL</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>Cytarabine</mesh_term>
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Brentuximab Vedotin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02243436
org study id: BRESHAP-GELTAMO.LH-2013
secondary id: 2014-000835-17
nct id: NCT02243436
lead sponsor: 
collaborator: 
has dmc: No
Phase I trial aimed to determine the Maximum Tolerable Dose of the BV in combination with
      ESHAP in relapsed/resistant Hodgkin Lymphona patients and to evaluate response to treatment
      with BV-ESHAP as salvage regimen prior to autologous stem cell transplantation.
Most patients suffering from Hodgkin's lymphoma (HL) can be successfully treated with
      standard chemo- and/or radiotherapy. However, in patients with refractory disease/relapsing
      after first line of therapy, conventional-dose chemotherapy regimens induce low remission
      rates, with long-term disease free survival not higher than 10% of patients.

      High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the
      standard treatment for these patients. This treatment approach results in long-term
      remissions in approximately 40-50% of relapsed patients, and in up to 25-30% of those with
      primary refractory disease. The possibility of a cure depends on several prognostic factors,
      however, in almost all series, the strongest prognostic factor has been the disease status
      before ASCT. Patients with HL who do not achieve complete remission (CR) after induction
      chemotherapy and those with unresponsive relapse have a very poor prognosis. Therefore, the
      choice of a very active pre-transplant salvage chemotherapy regimen is extremely important to
      improve results after ASCT. In addition, this activity should also be combined with a good
      stem cell mobilizing potential and low toxicity profiled.

      Several pre-transplant salvage regimens for refractory/relapsed HL are currently used with an
      overall response (OR) and CR rates ranging from 60% to 88% and from 17% to 49%, respectively.
      No randomized trial exists comparing the effectiveness of these regimens. ESHAP (Etoposide,
      Solumoderin (methylprednisolone), Ara-C (Cytarabine) and cisplatin) is one of the most
      commonly used regimens. ESHAP induces an OR and CR of 73% and 41%, respectively, with 5%
      toxic deaths. In the present study, a combination of ESHAP plus Brentuximab Vedotin (BV) is
      proposed as pre-transplant therapy with the aim to improve the CR rate before ASCT.

      HL is characterized by the presence of CD30-positive Hodgkin Reed-Sternberg cells. The
      antibody-drug conjugate BV delivers the highly potent antimicrotubule agent monomethyl
      auristatin E (MMAE) to CD30-positive malignant cells by binding specifically to CD30 on the
      cell surface and releasing MMAE inside the cell via lysosomal degradation.

      Binding of MMAE to tubulin results in apoptotic death of the CD30 expressing tumor cell.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended dose
time frame: Day 21 of cycle 1 (3 weeks after start of treatment)
description: During phase I, defined as the maximum Tolerable Dose of the BV in combination with ESHAP in relapsed/resistant HL patients.
measure: Global response rate prior to ASCT
time frame: 9 weeks (after start of treatment)
description: During phase II, Global response rate after BV-ESHAP as salvage regimen prior to ASCT.
measure: Complete response
time frame: 9 weeks (after start of treatment)
description: Percentage of patients with complete response rate after BV-ESHAP as salvage regimen prior to ASCT.
measure: Toxicity according to the CTC criteria
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
description: To determine the toxicity of BV-ESHAP regimen
measure: Stem cell mobilization capacity
time frame: After first or second cycle of treatment
description: To assess the stem cell mobilization capacity of the BV-ESHAP regimen: determine the expanse and effectiveness of the extraction of stem cells from peripheral blood.
measure: Transplant-related mortality (TRM)
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
measure: Overall Survival (OS)
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
description: Percentage of patients alive after first dose of treatment through follow-up
measure: Progression free survival (PFS)
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
description: Percentage of patients without progression of disease
measure: Event-Free Survival
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
description: Percentage of patients without event
measure: Time to HL Progression
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
measure: Disease-Free Survival
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
measure: Response Duration
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
description: Length of time between date of evidenced response and progression of disease or death
measure: Lymphoma-Specific Survival
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
measure: Time to Next Treatment
time frame: Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.
arm group label: BV-ESHAP
arm group type: Experimental
description: - 3 cycles every 21 days:
Brentuximab Vedotin, on day 1 (BV will be administered at three different doses 0.9mg/kg, 1.2mg/kg, 1.8mg/kg)
Etoposide 40 mg/m2/day, on days 1 to 4
Soludomerin (methylprednisolone) 250 mg/day, on days 1 to 4
Cisplatin 25 mg/m2/day, on days 1 to 4
Ara C (cytarabine) 2 g/m2, on day 5
- A fourth dose of BV will be given 21 days after the third BV dose during the evaluation of response before the transplant.
- Autologous peripheral blood stem cell transplant
- A fifth dose of BV (1.8mg/kg) will be given on between day 28 and 35 post-transplant, followed by two additional doses (1.8mg/kg) every 3 weeks, to complete a total of 7 BV infusions.
intervention type: Drug
intervention name: Brentuximab Vedotin
description: Brentuximab Vedotin, 0.9mg/kg, 1.2mg/kg, 1.8mg/kg, day 1
arm group label: BV-ESHAP
other name: ADCETRIS
intervention type: Drug
intervention name: Etoposide
description: Intravenose use, 40mg/m2/day, on days 1 to 4
arm group label: BV-ESHAP
intervention type: Drug
intervention name: Soludomerin
description: Intravenous use, 250mg/day, on days 1 to 4
arm group label: BV-ESHAP
other name: Methylprednisolone
intervention type: Drug
intervention name: Cisplatin
description: Intravenous use, 25mg/m2/day, on days 1 to 4
arm group label: BV-ESHAP
intervention type: Drug
intervention name: Ara C
description: Intravenous use, 2g/m2, day 5
arm group label: BV-ESHAP
other name: Cytarabine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ramón García-Sanz, MD
role: Study Chair
affiliation: University of Salamanca
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country: Spain
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Cytarabine
mesh term: Methylprednisolone
mesh term: Etoposide
mesh term: Brentuximab Vedotin
sharing ipd: No