<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/NCT03241017</url>
  </required_header>
  <id_info>
    <org_study_id>IDA-D Trial</org_study_id>
    <nct_id>NCT03241017</nct_id>
  </id_info>
  <brief_title>Durvalumab in DLBCL After Autologous Transplant</brief_title>
  <acronym>IDA-D</acronym>
  <official_title>A Phase II Trial Investigating the Benefit of Immunotherapy With Durvalumab After Autologous Transplant in High-risk Diffuse-large B-cell Lymphomas (the IDA-D Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial assess the progression-free survival (PFS) two years after autologous stem cell&#xD;
      transplantation (ASCT) in high-risk DLBCL patients receiving PD-L1 inhibition with&#xD;
      durvalumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background and Rationale:&#xD;
&#xD;
      Autologous stem cell transplantation (ASCT) is standard of care in the treatment concept of&#xD;
      adult patients with multiple myeloma (MM), malignant lymphomas (including diffuse large&#xD;
      B-cell lymphomas (DLBCL), mantle cell lymphomas, follicular lymphomas or T-cell lymphomas),&#xD;
      acute myeloid leukemia (AML) and relapsing germ cell tumors. The number of patients treated&#xD;
      with ASCT is steadily increasing, e.g. by +17% alone in Switzerland in the year 2015, to a&#xD;
      total of 464 ASCT per year in Switzerland. The Inselspital (University Hospital) in Berne is&#xD;
      the leading hospital in Switzerland for ASCT, with 145 ASCT in the year 2015. Among these 145&#xD;
      transplants, 31 patients had DLBCL.&#xD;
&#xD;
      The goal of treatment in DLBCL is definite cure. In DLBCL, the addition of anti-CD20&#xD;
      treatment to standard CHOP (Cyclophosphamid, Doxorubicin, Vincristine, Prednisone)&#xD;
      chemotherapy has improved the cure rate after R-CHOP (Rituximab-CHOP) first-line treatment.&#xD;
      Nevertheless, the disease is relapsing in roughly 20% of these patients. At relapse, patients&#xD;
      are treated with salvage chemotherapy such as the R-DHAP (Rituximab, Dexamethasone,&#xD;
      Cisplatin,Cytarabine), or R-ICE (Rituximab,Ifosfamide, Carboplatin, Etoposide) regimens,&#xD;
      followed by BEAM (BCNU, Etoposide, Cytarabine, Melphalan) or BeEAM (Bendamustin, Etoposide,&#xD;
      Cyclophosphamide, Melphalan) high-dose chemotherapy supported with ASCT. The overall survival&#xD;
      rate at the Inselspital Bern and elsewhere at two years for DLBCL patients after ASCT is 60%,&#xD;
      and, therefore, improving outcome of such patients remains an unmet clinical need. This is&#xD;
      particularly true in high-risk DLBCL patients, such as in DLBCL patients relapsing within 12&#xD;
      months after first-line treatment as well as in DLBCL patients not achieving a (first or&#xD;
      second) complete remission (CR) after induction treatment before ASCT. PFS at two years for&#xD;
      such high-risk lymphoma patients is 50% at the investigators' institution.&#xD;
&#xD;
      Immunotherapy (such as with PD-L1 inhibition) after ASCT is a promising approach to&#xD;
      potentially improve results after ASCT. A first study applying PD-1 inhibition with three&#xD;
      applications (every 42 days) of Pidilizumab started between days 30 and 90 after ASCT showed&#xD;
      a promising progression-free survival rate of 72% in relapsing DLBCL patients at 16 months&#xD;
      after the first Pidilizumab application. These data suggest that immunotherapy after ASCT has&#xD;
      the potential to a meaningful improvement of survival rates in DLBCL patients after ASCT.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The primary objective of this Trial is to show a progression-free survival of 70% two years&#xD;
      after autologous stem cell transplantation (ASCT) in high-risk DLBCL patients receiving PD-L1&#xD;
      inhibition with durvalumab.&#xD;
&#xD;
      Study Duration:&#xD;
&#xD;
      The 46 patients needed in this study will be included within 24 months. Additional 24 months&#xD;
      will be needed until the last study patient reaches PFS at 2 years. Accordingly, the total&#xD;
      study duration is expected to be 48 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Celgene withdrew the support for this study (Durvalumab cannot be provided)&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 2017</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">October 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Interventional, prospective, single-center, open-label, single-arm, non-comparative and non-randomized phase II study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Number of Patients with Progression-free survival (PFS) two years after autologous stem cell transplantation (ASCT) in high-risk DLBCL patients receiving PD-L1 inhibition with durvalumab.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response Rate</measure>
    <time_frame>24 months</time_frame>
    <description>The Response (Tumor measurement) to durvalumab treatment will be assessed by PET-CT 24 months after ASCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>24 months</time_frame>
    <description>Number of Patients experiencing Toxicity (Adverse Events)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic engraftment</measure>
    <time_frame>24 months</time_frame>
    <description>Number of days until hematological engraftment. Hematologic engraftment after high-dose chemotherapy induced myelosuppression is defined as the first day of neutrophils rising again above 0.5 G/l, and of platelets rising again above 20 G/L in the absence of platelet transfusions in the previous 3 days. Hematological values will be performed every 4 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The quality of life</measure>
    <time_frame>24 months</time_frame>
    <description>The EORTC Q30 questionnaire will be given to patients before the first durvalumab administration, and after 3, 12 and 24 months after ASCT to assess quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>24 months</time_frame>
    <description>Number of Patient alive at 24 months</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Lymphoma, Large B-Cell, Diffuse</condition>
  <arm_group>
    <arm_group_label>Durvalumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab 1500 mg (day 1) given every 4 weeks for a total of 12 applications (1 year).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Immunotherapy with Durvalumab after ASCT</description>
    <arm_group_label>Durvalumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with any types of DLBCL (de novo or transformed), including double-hit&#xD;
             lymphomas, grey zone lymphomas, double or triple expressor lymphomas, unclassifiable&#xD;
             aggressive lymphoma types or aggressive lymphomas.&#xD;
&#xD;
          -  Lymphoma patients (as listed above) in first remission considered as high-risk and&#xD;
             defined as lymphoma patients not achieving a complete first remission after induction&#xD;
             treatment before subsequent ASCT; or patients in second remission considered as&#xD;
             high-risk and defined as lymphoma patients relapsing within 12 months after first-line&#xD;
             treatment or lymphoma patients not achieving a complete second remission after salvage&#xD;
             treatment before subsequent ASCT.&#xD;
&#xD;
          -  ECOG 0-2&#xD;
&#xD;
          -  Age 18-75 years&#xD;
&#xD;
          -  Female patients of child-bearing potential must have a negative pregnancy test (urine&#xD;
             or serum) within 14 days prior to study treatment, and they must implement adequate&#xD;
             measures (hormonal treatment p.o. or i.m., intra uterine surgical devices, or latex&#xD;
             condoms) to avoid pregnancy during study treatment and for additional 12 months.&#xD;
&#xD;
          -  Patients must have given voluntary written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other types of malignant lymphomas&#xD;
&#xD;
          -  Previous treatment with antibodies against PD-(L)1&#xD;
&#xD;
          -  Symptomatic CNS (Central Nervous System) involvement by lymphoma&#xD;
&#xD;
          -  Active infection requiring antibiotic/antifungal treatment&#xD;
&#xD;
          -  Lack of patient cooperation to allow study treatment as outlined in this protocol&#xD;
&#xD;
          -  Pregnancy or lactating female patients&#xD;
&#xD;
          -  Major surgery less than 30 days before start of treatment&#xD;
&#xD;
          -  Contraindications and hypersensitivity to any of the active chemotherapy compounds&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Pabst, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Departement of Medical Oncology, University Hospital Berne</affiliation>
  </overall_official>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>April 5, 2018</last_update_submitted>
  <last_update_submitted_qc>April 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 9, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diffuse Large B-Cell Lymphoma</keyword>
  <keyword>Double-hit Lymphomas</keyword>
  <keyword>Grey Zone Lymphomas</keyword>
  <keyword>Double or Triple Expressor Lymphomas</keyword>
  <keyword>Unclassifiable Aggressive Lymphoma types</keyword>
  <keyword>Aggressive Lymphomas</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</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/NCT03241017
org study id: IDA-D Trial
nct id: NCT03241017
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The trial assess the progression-free survival (PFS) two years after autologous stem cell
      transplantation (ASCT) in high-risk DLBCL patients receiving PD-L1 inhibition with
      durvalumab.
Background and Rationale:

      Autologous stem cell transplantation (ASCT) is standard of care in the treatment concept of
      adult patients with multiple myeloma (MM), malignant lymphomas (including diffuse large
      B-cell lymphomas (DLBCL), mantle cell lymphomas, follicular lymphomas or T-cell lymphomas),
      acute myeloid leukemia (AML) and relapsing germ cell tumors. The number of patients treated
      with ASCT is steadily increasing, e.g. by +17% alone in Switzerland in the year 2015, to a
      total of 464 ASCT per year in Switzerland. The Inselspital (University Hospital) in Berne is
      the leading hospital in Switzerland for ASCT, with 145 ASCT in the year 2015. Among these 145
      transplants, 31 patients had DLBCL.

      The goal of treatment in DLBCL is definite cure. In DLBCL, the addition of anti-CD20
      treatment to standard CHOP (Cyclophosphamid, Doxorubicin, Vincristine, Prednisone)
      chemotherapy has improved the cure rate after R-CHOP (Rituximab-CHOP) first-line treatment.
      Nevertheless, the disease is relapsing in roughly 20% of these patients. At relapse, patients
      are treated with salvage chemotherapy such as the R-DHAP (Rituximab, Dexamethasone,
      Cisplatin,Cytarabine), or R-ICE (Rituximab,Ifosfamide, Carboplatin, Etoposide) regimens,
      followed by BEAM (BCNU, Etoposide, Cytarabine, Melphalan) or BeEAM (Bendamustin, Etoposide,
      Cyclophosphamide, Melphalan) high-dose chemotherapy supported with ASCT. The overall survival
      rate at the Inselspital Bern and elsewhere at two years for DLBCL patients after ASCT is 60%,
      and, therefore, improving outcome of such patients remains an unmet clinical need. This is
      particularly true in high-risk DLBCL patients, such as in DLBCL patients relapsing within 12
      months after first-line treatment as well as in DLBCL patients not achieving a (first or
      second) complete remission (CR) after induction treatment before ASCT. PFS at two years for
      such high-risk lymphoma patients is 50% at the investigators' institution.

      Immunotherapy (such as with PD-L1 inhibition) after ASCT is a promising approach to
      potentially improve results after ASCT. A first study applying PD-1 inhibition with three
      applications (every 42 days) of Pidilizumab started between days 30 and 90 after ASCT showed
      a promising progression-free survival rate of 72% in relapsing DLBCL patients at 16 months
      after the first Pidilizumab application. These data suggest that immunotherapy after ASCT has
      the potential to a meaningful improvement of survival rates in DLBCL patients after ASCT.

      Objective:

      The primary objective of this Trial is to show a progression-free survival of 70% two years
      after autologous stem cell transplantation (ASCT) in high-risk DLBCL patients receiving PD-L1
      inhibition with durvalumab.

      Study Duration:

      The 46 patients needed in this study will be included within 24 months. Additional 24 months
      will be needed until the last study patient reaches PFS at 2 years. Accordingly, the total
      study duration is expected to be 48 months.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Interventional, prospective, single-center, open-label, single-arm, non-comparative and non-randomized phase II study
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival
time frame: 24 months
description: Number of Patients with Progression-free survival (PFS) two years after autologous stem cell transplantation (ASCT) in high-risk DLBCL patients receiving PD-L1 inhibition with durvalumab.
measure: Response Rate
time frame: 24 months
description: The Response (Tumor measurement) to durvalumab treatment will be assessed by PET-CT 24 months after ASCT
measure: Adverse Events
time frame: 24 months
description: Number of Patients experiencing Toxicity (Adverse Events)
measure: Hematologic engraftment
time frame: 24 months
description: Number of days until hematological engraftment. Hematologic engraftment after high-dose chemotherapy induced myelosuppression is defined as the first day of neutrophils rising again above 0.5 G/l, and of platelets rising again above 20 G/L in the absence of platelet transfusions in the previous 3 days. Hematological values will be performed every 4 weeks
measure: The quality of life
time frame: 24 months
description: The EORTC Q30 questionnaire will be given to patients before the first durvalumab administration, and after 3, 12 and 24 months after ASCT to assess quality of life.
measure: Overall Survival
time frame: 24 months
description: Number of Patient alive at 24 months
arm group label: Durvalumab
arm group type: Experimental
description: Durvalumab 1500 mg (day 1) given every 4 weeks for a total of 12 applications (1 year).
intervention type: Drug
intervention name: Durvalumab
description: Immunotherapy with Durvalumab after ASCT
arm group label: Durvalumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Thomas Pabst, MD
role: Study Chair
affiliation: Departement of Medical Oncology, University Hospital Berne
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Durvalumab