<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/NCT03302728</url>
  </required_header>
  <id_info>
    <org_study_id>17/34</org_study_id>
    <nct_id>NCT03302728</nct_id>
  </id_info>
  <brief_title>Brentuximab Vedotin and Lenalidomide in Patients With Relapsed/ Refractory T-cell Lymphoma or Hodgkin Lymphoma</brief_title>
  <acronym>EpiBrentlen</acronym>
  <official_title>A Phase 1b Study of Brentuximab Vedotin and Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-cell Lymphoma, CD30-positive Peripheral T-cell Lymphoma, or CD30-positive Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter MacCallum Cancer Centre, Australia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peter MacCallum Cancer Centre, Australia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is investigating the combination of Brentuximab vedotin and lenalidomide in the&#xD;
      treatment of relapsed/refractory peripheral T cell lymphoma or cutaneous T cell lymphoma or&#xD;
      Hodgkin lymphoma.&#xD;
&#xD;
      It is hypothesised that lenalidomide may augment the actions of Brentuximab vedotin in these&#xD;
      patient groups. The primary objective of the study is to determine the maximum tolerated dose&#xD;
      of the combination treatment, which can be used in subsequent studies. The study will also&#xD;
      investigate disease response and survival.&#xD;
&#xD;
      Participants will receive Brentuximab vedotin (once every 21 days i.e. 1 cycle) and&#xD;
      lenalidomide (daily from day 1 -14 of each cycle) for a maximum of 48 weeks and will be&#xD;
      followed for a subsequent 6 months after the end of treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 30, 2018</start_date>
  <completion_date type="Actual">August 2, 2021</completion_date>
  <primary_completion_date type="Actual">August 2, 2021</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>This is a single arm dose escalation study. There are four dose levels for the combination of Brentuximab vedotin and Lenalidomide considered during the dose escalation.&#xD;
Starting Dose Level 1: Brentuximab vedotin 1.8mg/kg q21 days &amp; Lenalidomide 15 mg daily (D1-14)&#xD;
The dose can be decreased as follows:&#xD;
Level -2 Brentuximab vedotin 1.2mg/kg q21 days &amp; Lenalidomide 5 mg daily (D1-14)&#xD;
Level -1 Brentuximab vedotin 1.2mg/kg q21 days &amp; Lenalidomide 10 mg daily (D1-14)&#xD;
or the dose can be escalated as follows:&#xD;
Level 2 Brentuximab vedotin 1.8mg/kg q21 days &amp; Lenalidomide 25 mg daily (D1-14)&#xD;
Patients will be assigned a starting dose by the safety committee; this will be communicated by the PI and/or their designated sub-investigator prior to planned Cycle1 Day 1 for each patient.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2D) of the combination of lenalidomide and brentuximab vedotin</measure>
    <time_frame>70 weeks</time_frame>
    <description>Maximum tolerated dose, dose-limiting toxicities of the combination therapy, and recommended phase 2 dose, in patients with relapsed/refractory cutaneous T-cell lymphoma, CD30-positive Hodgkin lymphoma and CD30-positive peripheral T-cell lymphoma. The MTD is defined as the highest dose level at which the incidence of DLT was less than 33%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety profile of the combination of lenalidomide and brentuximab vedotin</measure>
    <time_frame>70 weeks</time_frame>
    <description>Toxicities measured using CTCAE V4.03.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment intensity.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Treatment intensity defined as the actual total dose received divided by the actual treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>70 weeks</time_frame>
    <description>Objective response, defined as achieving either complete response (CR) or partial response (PR) at some stage from time of commencement of treatment until conclusion of period of follow-up (maximum 16 cycles of treatment followed by 6 months of follow-up), or until time of documented progressive disease (defined as clinical and/or radiologic progression).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytostatic response.</measure>
    <time_frame>70 weeks</time_frame>
    <description>Cytostatic response, defined as achieving complete response (CR), partial response (PR) or stable disease (SD) lasting &gt;6 months from time of commencement of treatment until progressive disease (PD).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event free survival.</measure>
    <time_frame>70 weeks</time_frame>
    <description>Event free survival (EFS), defined as the time from commencement of treatment to date of early discontinuation of treatment due to toxicity, date of documented disease progression at any site, or date of death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>70 weeks</time_frame>
    <description>Overall survival (OS), defined as the time from commencement of treatment to the date of death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Lymphoma, T-Cell, Cutaneous</condition>
  <condition>Lymphoma, T-Cell, Peripheral</condition>
  <condition>Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Lenalidomide &amp; brentuximab vedotin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Brentuximab vedotin 1.8mg/Kg Lenalidomide 15 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide 15mg</intervention_name>
    <description>At commencement of study : Lenalidomide will commence at 15 mg daily for days 1-14 of each cycle. Maximum number of cycles = 16. This is a dose finding study so doses will be adjusted depending on toxicity assessment over the course of the study. Dose may vary from 5 mg -25 mg daily depending on dose escalation results and recommendation of safety committee</description>
    <arm_group_label>Lenalidomide &amp; brentuximab vedotin</arm_group_label>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin 1.8 mg/Kg</intervention_name>
    <description>At commencement of study : Brentuximab vedotin 1.8mg/kg IV on day 1, repeated every 21 days. Maximum number of cycles = 16. This is a dose finding study so doses will be adjusted depending on toxicity assessment over the course of the study. Dose may be either 1.2 mg/Kg q21 days or 1.8 mg/kg q21 days depending on dose escalation results and recommendation of safety committee</description>
    <arm_group_label>Lenalidomide &amp; brentuximab vedotin</arm_group_label>
    <other_name>Adcetris</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients of 18 years or older.&#xD;
&#xD;
          2. Patient must have a diagnosis of a CD30+ Hodgkin Lymphoma or CD30+ peripheral T-cell&#xD;
             lymphoma. Patients with either Hodgkin lymphoma or T-cell lymphoma must have&#xD;
             expression of CD30 in ≥10% of lymphoma cells. Patients with CTCL will be considered&#xD;
             for inclusion even if CD30 immunohistochemical staining with BerH2 antibody is low or&#xD;
             negligible (&lt;10%).&#xD;
&#xD;
               1. Peripheral T-cell lymphoma: patients must be considered relapsed or refractory&#xD;
                  after at least one prior chemotherapeutic regimen or be considered by the&#xD;
                  investigator to be not suitable for chemotherapy&#xD;
&#xD;
               2. Cutaneous T-cell lymphoma: patients must be relapsed or refractory to one prior&#xD;
                  systemic therapy or be considered by the investigator to be not suitable for&#xD;
                  chemotherapy&#xD;
&#xD;
               3. Patients with Hodgkin lymphoma and one of the following:&#xD;
&#xD;
             i. Relapsed or refractory after at least 2 prior chemotherapy-containing regimens&#xD;
             ii.Considered unsuitable for chemotherapy&#xD;
&#xD;
          3. Voluntary written informed consent must be given before performance of any study-&#xD;
             related procedure.&#xD;
&#xD;
          4. 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 6 months after the last dose of study drug, or agrees to&#xD;
             completely abstain from heterosexual intercourse.&#xD;
&#xD;
          5. Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to&#xD;
             practice effective barrier contraception during the entire study period and through 6&#xD;
             months after the last dose of study drug, or agrees to completely abstain from&#xD;
             heterosexual intercourse.&#xD;
&#xD;
          6. Performance status of ECOG ≤2.&#xD;
&#xD;
          7. Clinical laboratory values as specified below. Blood tests must be within 10 days of&#xD;
             patient registration:&#xD;
&#xD;
               -  Absolute neutrophil count &gt;1.5 x109/L, or &gt;1.0 x109/L in the setting of known&#xD;
                  marrow involvement by tumour.&#xD;
&#xD;
               -  Platelet count ≥75x109/L.&#xD;
&#xD;
               -  Total bilirubin must be &lt; 1.5 x the upper limit of the normal (ULN) unless the&#xD;
                  elevation is known to be due to Gilbert syndrome.&#xD;
&#xD;
               -  ALT or AST must be &lt; 2.5 x the upper limit of the normal range. AST or ALT may be&#xD;
                  elevated up to 5 times the ULN if their elevation can be reasonably ascribed to&#xD;
                  the presence of haematologic/solid tumor in liver.&#xD;
&#xD;
               -  Serum creatinine must be &lt; 150 µmol/L and/or creatinine clearance or calculated&#xD;
                  creatinine clearance &gt; 40 mL/minute.&#xD;
&#xD;
               -  Haemoglobin must be ≥ 80g/L.&#xD;
&#xD;
          8. Patients must have fully recovered from the acute toxic effects of all prior&#xD;
             chemotherapy, immunotherapy, or radiotherapy (except alopecia) prior to registration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female patients who are both lactating and breast-feeding or have a positive serum&#xD;
             pregnancy test during the screening period or a positive pregnancy test on planned&#xD;
             cycle 1, day 1 prior to first dose of study drug.&#xD;
&#xD;
          2. Any serious medical or psychiatric illness that could, in the investigator's opinion,&#xD;
             potentially interfere with the completion of treatment according to the protocol.&#xD;
&#xD;
          3. Symptomatic neurologic disease compromising normal activities of daily living or&#xD;
             requiring medication/s, including signs or symptoms of Progressive Multifocal&#xD;
             Leucoencephalopathy (PML).&#xD;
&#xD;
          4. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2 at&#xD;
             registration.&#xD;
&#xD;
          5. Known history of any of the following cardiovascular conditions&#xD;
&#xD;
               1. New York Heart Association (NYHA) Class III or IV heart failure (see Appendix&#xD;
                  18.1).&#xD;
&#xD;
               2. Evidence of current uncontrolled cardiovascular conditions, including cardiac&#xD;
                  arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic&#xD;
                  evidence of acute ischemia or active conduction system abnormalities.&#xD;
&#xD;
               3. A left-ventricular ejection fraction &lt;50%&#xD;
&#xD;
          6. Any active systemic viral, bacterial, or fungal infection requiring systemic&#xD;
             intravenous antibiotics or systemic antifungal therapies within 2 weeks prior to&#xD;
             registration.&#xD;
&#xD;
          7. Patients that have not completed any prior treatment chemotherapy and/or other&#xD;
             investigational agents within at least 5 half-lives of last dose of that prior&#xD;
             treatment.&#xD;
&#xD;
          8. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient&#xD;
             contained in the drug formulation of brentuximab vedotin or lenalidomide.&#xD;
&#xD;
          9. Known human immunodeficiency virus (HIV) positive.&#xD;
&#xD;
         10. Known hepatitis B surface antigen (HBsAg)-positive, or known or suspected active&#xD;
             hepatitis C infection. Patients who are Hepatitis B core antibody positive with no&#xD;
             evidence of active disease, i.e.&#xD;
&#xD;
             HBsAg negative/ negative hepatitis B viral load, will still be considered eligible for&#xD;
             inclusion, but must receive viral suppressive therapy for the duration of the trial.&#xD;
&#xD;
         11. Active systemic malignancy likely to require treatment within the next two years, or&#xD;
             previous diagnosis of another malignancy with residual disease. Patients with&#xD;
             non-melanoma skin cancer or carcinoma- in-situ of any type are not excluded if they&#xD;
             have undergone complete resection.&#xD;
&#xD;
         12. Previous exposure to brentuximab vedotin.&#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>Michael Dickinson, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peter MacCallum Cancer Centre, Australia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>October 1, 2017</study_first_submitted>
  <study_first_submitted_qc>October 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CD 30 positive, relapsed, refractory</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>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Cutaneous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenalidomide</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/NCT03302728
org study id: 17/34
nct id: NCT03302728
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study is investigating the combination of Brentuximab vedotin and lenalidomide in the
      treatment of relapsed/refractory peripheral T cell lymphoma or cutaneous T cell lymphoma or
      Hodgkin lymphoma.

      It is hypothesised that lenalidomide may augment the actions of Brentuximab vedotin in these
      patient groups. The primary objective of the study is to determine the maximum tolerated dose
      of the combination treatment, which can be used in subsequent studies. The study will also
      investigate disease response and survival.

      Participants will receive Brentuximab vedotin (once every 21 days i.e. 1 cycle) and
      lenalidomide (daily from day 1 -14 of each cycle) for a maximum of 48 weeks and will be
      followed for a subsequent 6 months after the end of treatment.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a single arm dose escalation study. There are four dose levels for the combination of Brentuximab vedotin and Lenalidomide considered during the dose escalation.
Starting Dose Level 1: Brentuximab vedotin 1.8mg/kg q21 days & Lenalidomide 15 mg daily (D1-14)
The dose can be decreased as follows:
Level -2 Brentuximab vedotin 1.2mg/kg q21 days & Lenalidomide 5 mg daily (D1-14)
Level -1 Brentuximab vedotin 1.2mg/kg q21 days & Lenalidomide 10 mg daily (D1-14)
or the dose can be escalated as follows:
Level 2 Brentuximab vedotin 1.8mg/kg q21 days & Lenalidomide 25 mg daily (D1-14)
Patients will be assigned a starting dose by the safety committee; this will be communicated by the PI and/or their designated sub-investigator prior to planned Cycle1 Day 1 for each patient.
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2D) of the combination of lenalidomide and brentuximab vedotin
time frame: 70 weeks
description: Maximum tolerated dose, dose-limiting toxicities of the combination therapy, and recommended phase 2 dose, in patients with relapsed/refractory cutaneous T-cell lymphoma, CD30-positive Hodgkin lymphoma and CD30-positive peripheral T-cell lymphoma. The MTD is defined as the highest dose level at which the incidence of DLT was less than 33%.
measure: Safety profile of the combination of lenalidomide and brentuximab vedotin
time frame: 70 weeks
description: Toxicities measured using CTCAE V4.03.
measure: Treatment intensity.
time frame: 48 weeks
description: Treatment intensity defined as the actual total dose received divided by the actual treatment period.
measure: Objective response rate
time frame: 70 weeks
description: Objective response, defined as achieving either complete response (CR) or partial response (PR) at some stage from time of commencement of treatment until conclusion of period of follow-up (maximum 16 cycles of treatment followed by 6 months of follow-up), or until time of documented progressive disease (defined as clinical and/or radiologic progression).
measure: Cytostatic response.
time frame: 70 weeks
description: Cytostatic response, defined as achieving complete response (CR), partial response (PR) or stable disease (SD) lasting >6 months from time of commencement of treatment until progressive disease (PD).
measure: Event free survival.
time frame: 70 weeks
description: Event free survival (EFS), defined as the time from commencement of treatment to date of early discontinuation of treatment due to toxicity, date of documented disease progression at any site, or date of death from any cause, whichever occurs first.
measure: Overall survival
time frame: 70 weeks
description: Overall survival (OS), defined as the time from commencement of treatment to the date of death from any cause.
arm group label: Lenalidomide & brentuximab vedotin
arm group type: Experimental
description: Brentuximab vedotin 1.8mg/Kg Lenalidomide 15 mg
intervention type: Drug
intervention name: Lenalidomide 15mg
description: At commencement of study : Lenalidomide will commence at 15 mg daily for days 1-14 of each cycle. Maximum number of cycles = 16. This is a dose finding study so doses will be adjusted depending on toxicity assessment over the course of the study. Dose may vary from 5 mg -25 mg daily depending on dose escalation results and recommendation of safety committee
arm group label: Lenalidomide & brentuximab vedotin
other name: Revlimid
intervention type: Drug
intervention name: Brentuximab Vedotin 1.8 mg/Kg
description: At commencement of study : Brentuximab vedotin 1.8mg/kg IV on day 1, repeated every 21 days. Maximum number of cycles = 16. This is a dose finding study so doses will be adjusted depending on toxicity assessment over the course of the study. Dose may be either 1.2 mg/Kg q21 days or 1.8 mg/kg q21 days depending on dose escalation results and recommendation of safety committee
arm group label: Lenalidomide & brentuximab vedotin
other name: Adcetris
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Dickinson, Dr
role: Principal Investigator
affiliation: Peter MacCallum Cancer Centre, Australia
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Lymphoma, T-Cell, Cutaneous
mesh term: Lenalidomide
mesh term: Brentuximab Vedotin
sharing ipd: No