<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/NCT04506320</url>
  </required_header>
  <id_info>
    <org_study_id>GITMO-NEW_ALLO_MM</org_study_id>
    <nct_id>NCT04506320</nct_id>
  </id_info>
  <brief_title>Novel Drugs After Allo-HSCT in Patients With Multiple Myeloma</brief_title>
  <acronym>NEW_ALL_MM</acronym>
  <official_title>Novel Drugs (Immuno-modulating Agents, Protesome Inhibitors, Monoclonal Antibodies) After Allogeneic Transplant in Patients With Multiple Myeloma: an Observational Retrospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gruppo Italiano Trapianto di Midollo Osseo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Azienda Ospedaliero-Universitaria Careggi</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Gruppo Italiano Trapianto di Midollo Osseo</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>
      This is a retrospective observational study of epidemiological surveillance, multicenter,&#xD;
      non-profit, spontaneous, Italian on patients submitted to allo-HSCT among Italian Transplant&#xD;
      Centers GITMO.&#xD;
&#xD;
      This study will evaluate all consecutive adult patients who received novel drugs after&#xD;
      hematopoietic stem cell transplantation from related and unrelated donors between January 1,&#xD;
      2009 to December 31, 2018 in GITMO-affiliated Centers.&#xD;
&#xD;
      This study will evaluate approximately 300 subjects (with competitive enrolment) from GITMO&#xD;
      investigational centers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a retrospective, observational multicenter, non-profit, spontaneous, Italian study&#xD;
      organized under the auspices of the Gruppo Italiano Trapianti di Midollo Osseo that involves&#xD;
      the principal Centers active in transplantation of any kind of hematopoietic stem cells in&#xD;
      Italy.&#xD;
&#xD;
      Multiple myeloma is a neoplastic plasma cell disorder characterized by clonal proliferation&#xD;
      of malignant plasma cells in the bone marrow and the presence of a monoclonal protein in the&#xD;
      blood and/or urine, resulting in myeloma-defining events. The outcomes of patients with&#xD;
      Multiple myeloma have improved significantly due to the introduction of novel agents;&#xD;
      however, the disease remains incurable for most patients. Allogeneic hematopoietic stem cell&#xD;
      transplantation has a curative potential by employing the donor immune system to eradicate&#xD;
      malignant plasmacells, commonly referred to as the graft-versus-myeloma effect. However,&#xD;
      despite this proven graft-versus-myeloma effect, the associated severe toxicity as&#xD;
      treatment-related mortality mainly induced by myeloablative conditioning strategies and,&#xD;
      above all, high relapse rate are important concerns and the place and role of allogeneic&#xD;
      hematopoietic stem cell transplantation in Multiple myeloma remain challenging. In this&#xD;
      regard, the International Myeloma Working Group together with the Blood and Marrow Transplant&#xD;
      Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the&#xD;
      European Society of Blood and Marrow Transplantation agreed that allogeneic hematopoietic&#xD;
      stem cell transplantation should be considered an appropriate therapy for all eligible&#xD;
      patients with early relapse (occurring within 24 months) after primary therapy that included&#xD;
      the new proteasome inhibitors and immunomodulatory drugs and autologous stem cell&#xD;
      transplantation and/or high-risk features.&#xD;
&#xD;
      allogeneic hematopoietic stem cell transplantation might represent an interesting platform&#xD;
      for the use of rescue treatments based on novel drugs after the relapse. This observation&#xD;
      might reflect the fact that allogeneic hematopoietic stem cell transplantation can modify the&#xD;
      biology of the disease, directly targeting the myelomatous plasma cells as well as the&#xD;
      microenvironment, and the well-documented graft-versus-myeloma effect induced by reactive&#xD;
      allogeneic T cells may persist after relapse and contribute to an enhanced disease response.&#xD;
      Novel agent-based combinations should be considered also in association with donor lymphocyte&#xD;
      infusion. Monoclonal antibodies have emerged as the new option for treatment of patients with&#xD;
      relapsed and refractory MM.&#xD;
&#xD;
      This scenario might represent a good opportunity to evaluate the efficacy of novel agents&#xD;
      before and after transplantation.&#xD;
&#xD;
      The general objectives of this study are to retrospectively investigate the outcome of&#xD;
      patients with Mieloma multiple after allogeneic hematopoietic stem cell transplantation and&#xD;
      the first purpose of this study is to describe the overall survival at 2 years after&#xD;
      allogeneic hematopoietic stem cell transplantation.&#xD;
&#xD;
      The secondary objectives are described Progression Free Survival, the incidence of acute and&#xD;
      chronic graft versus host disease, describe the hematological and non-hematological toxicity&#xD;
      of drugs administered after allogeneic hematopoietic stem cell transplantation and describe&#xD;
      the Non-relapse- mortality.&#xD;
&#xD;
      Data will be stored using database Promise and specific e-CRFs. Data Center will perform&#xD;
      extensive consistency checks and issue. Query Forms in case of inconsistent data. Follow-up&#xD;
      period for the evaluation of survival will be from the date of transplant until 24 months&#xD;
      post-transplant or death.&#xD;
&#xD;
      The study will be conducted according to the principles of Good Clinical Practice, the&#xD;
      current Italian and European laws and regulations, in agreement with the declaration of&#xD;
      Helsinki. The protocol has been written and the study will be conducted according to The&#xD;
      International Council for Harmonisation of Technical Requirements for Pharmaceuticals for&#xD;
      Human Use Harmonized Tripartite Guideline for Good Clinical Practice, issued by the European&#xD;
      Union. The responsible Local Ethical Committee approval must be obtained before starting the&#xD;
      trial. A copy of the patient informed consent form must be submitted to the appropriate&#xD;
      authority or committee, together with the protocol for written approval. Written approval of&#xD;
      the protocol and informed consent by the responsible and appropriate authority or committee&#xD;
      must be obtained prior to recruitment of patients to the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 17, 2021</start_date>
  <completion_date type="Actual">January 31, 2023</completion_date>
  <primary_completion_date type="Actual">January 31, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>these outcome measures will be assessed at 2 year from transplant</time_frame>
    <description>OS is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival 1 (PFS1)</measure>
    <time_frame>these outcome measures will be assessed at 2 year from transplant</time_frame>
    <description>PFS1 is defined as the time interval from allo-HSCT until the first disease progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival 2 (PFS2)</measure>
    <time_frame>These outcome measures will be assessed at 2 year from transplant</time_frame>
    <description>PFS2 is defined as the time interval from allo-HSCT until the second disease progression or death, estimating the impact of both first- and second-line therapies on outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Graft-versus-Host Disease (aGVHD)</measure>
    <time_frame>These outcome measures will be assessed at 100 days from transplant</time_frame>
    <description>cumulative incidence of acute GvHD (grade II-IV)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic Graft-versus-Host Disease (cGVHD)</measure>
    <time_frame>These outcome measures will be assessed at 2 year from transplant</time_frame>
    <description>Cumulative incidence and severity of chronic graft-versus-host disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-Relapse Mortality (NRM)</measure>
    <time_frame>These outcome measures will be assessed at 2 year from transplantation</time_frame>
    <description>Cumulative incidence of Non-Relapse Mortality is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">202</enrollment>
  <condition>Multiple Myeloma</condition>
  <condition>Stem Cell Transplant</condition>
  <arm_group>
    <arm_group_label>Patients with Multiple myeloma</arm_group_label>
    <description>Adult with diagnosis of multiple myeloma treated with Allo-HSCT from related - HLA identical or volunteer unrelated donor or haploidentical related donor performed from January 1, 2009 to december 31, 2018</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with Multiple Myeloma who had received novel drugs after allogeneic&#xD;
        transplantation (allo-HSCT) from related and unrelated donor between January 1, 2009 to&#xD;
        December 31, 2018.&#xD;
&#xD;
        Each enrolled patient will have a two-year of follow-up from the allogeneic transplant date&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria Written and signed study informed consent Multiple myeloma Allogeneic&#xD;
        transplantation from related - HLA identical Allogeneic transplantation from volunteer&#xD;
        unrelated donor allogeneic transplantation from haploidentical related donor Myeloablative&#xD;
        or reduced intensity conditioning regimen&#xD;
&#xD;
        Exclusion Criteria Second or further allogeneic transplant Plasma cell leukemia Non&#xD;
        measurable disease&#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>Chiara Nozzoli</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliero-Universitaria Careggi, Firenze</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Azienda Ospedaliera di Careggi</name>
      <address>
        <city>Firenze</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Ematologica - Policlinico Universitario</name>
      <address>
        <city>Udine</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 7, 2020</study_first_submitted>
  <study_first_submitted_qc>August 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>March 9, 2023</last_update_submitted>
  <last_update_submitted_qc>March 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Allogeneic haematopoietic stem cell transplantation</keyword>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Immuno-modulating agents</keyword>
  <keyword>Protesome inhibitors</keyword>
  <keyword>Monoclonal antibodies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_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/NCT04506320
org study id: GITMO-NEW_ALLO_MM
nct id: NCT04506320
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a retrospective observational study of epidemiological surveillance, multicenter,
      non-profit, spontaneous, Italian on patients submitted to allo-HSCT among Italian Transplant
      Centers GITMO.

      This study will evaluate all consecutive adult patients who received novel drugs after
      hematopoietic stem cell transplantation from related and unrelated donors between January 1,
      2009 to December 31, 2018 in GITMO-affiliated Centers.

      This study will evaluate approximately 300 subjects (with competitive enrolment) from GITMO
      investigational centers.
This is a retrospective, observational multicenter, non-profit, spontaneous, Italian study
      organized under the auspices of the Gruppo Italiano Trapianti di Midollo Osseo that involves
      the principal Centers active in transplantation of any kind of hematopoietic stem cells in
      Italy.

      Multiple myeloma is a neoplastic plasma cell disorder characterized by clonal proliferation
      of malignant plasma cells in the bone marrow and the presence of a monoclonal protein in the
      blood and/or urine, resulting in myeloma-defining events. The outcomes of patients with
      Multiple myeloma have improved significantly due to the introduction of novel agents;
      however, the disease remains incurable for most patients. Allogeneic hematopoietic stem cell
      transplantation has a curative potential by employing the donor immune system to eradicate
      malignant plasmacells, commonly referred to as the graft-versus-myeloma effect. However,
      despite this proven graft-versus-myeloma effect, the associated severe toxicity as
      treatment-related mortality mainly induced by myeloablative conditioning strategies and,
      above all, high relapse rate are important concerns and the place and role of allogeneic
      hematopoietic stem cell transplantation in Multiple myeloma remain challenging. In this
      regard, the International Myeloma Working Group together with the Blood and Marrow Transplant
      Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the
      European Society of Blood and Marrow Transplantation agreed that allogeneic hematopoietic
      stem cell transplantation should be considered an appropriate therapy for all eligible
      patients with early relapse (occurring within 24 months) after primary therapy that included
      the new proteasome inhibitors and immunomodulatory drugs and autologous stem cell
      transplantation and/or high-risk features.

      allogeneic hematopoietic stem cell transplantation might represent an interesting platform
      for the use of rescue treatments based on novel drugs after the relapse. This observation
      might reflect the fact that allogeneic hematopoietic stem cell transplantation can modify the
      biology of the disease, directly targeting the myelomatous plasma cells as well as the
      microenvironment, and the well-documented graft-versus-myeloma effect induced by reactive
      allogeneic T cells may persist after relapse and contribute to an enhanced disease response.
      Novel agent-based combinations should be considered also in association with donor lymphocyte
      infusion. Monoclonal antibodies have emerged as the new option for treatment of patients with
      relapsed and refractory MM.

      This scenario might represent a good opportunity to evaluate the efficacy of novel agents
      before and after transplantation.

      The general objectives of this study are to retrospectively investigate the outcome of
      patients with Mieloma multiple after allogeneic hematopoietic stem cell transplantation and
      the first purpose of this study is to describe the overall survival at 2 years after
      allogeneic hematopoietic stem cell transplantation.

      The secondary objectives are described Progression Free Survival, the incidence of acute and
      chronic graft versus host disease, describe the hematological and non-hematological toxicity
      of drugs administered after allogeneic hematopoietic stem cell transplantation and describe
      the Non-relapse- mortality.

      Data will be stored using database Promise and specific e-CRFs. Data Center will perform
      extensive consistency checks and issue. Query Forms in case of inconsistent data. Follow-up
      period for the evaluation of survival will be from the date of transplant until 24 months
      post-transplant or death.

      The study will be conducted according to the principles of Good Clinical Practice, the
      current Italian and European laws and regulations, in agreement with the declaration of
      Helsinki. The protocol has been written and the study will be conducted according to The
      International Council for Harmonisation of Technical Requirements for Pharmaceuticals for
      Human Use Harmonized Tripartite Guideline for Good Clinical Practice, issued by the European
      Union. The responsible Local Ethical Committee approval must be obtained before starting the
      trial. A copy of the patient informed consent form must be submitted to the appropriate
      authority or committee, together with the protocol for written approval. Written approval of
      the protocol and informed consent by the responsible and appropriate authority or committee
      must be obtained prior to recruitment of patients to the study.
observational model: Cohort
time perspective: Retrospective
measure: Overall Survival (OS)
time frame: these outcome measures will be assessed at 2 year from transplant
description: OS is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis
measure: Progression Free Survival 1 (PFS1)
time frame: these outcome measures will be assessed at 2 year from transplant
description: PFS1 is defined as the time interval from allo-HSCT until the first disease progression or death
measure: Progression Free Survival 2 (PFS2)
time frame: These outcome measures will be assessed at 2 year from transplant
description: PFS2 is defined as the time interval from allo-HSCT until the second disease progression or death, estimating the impact of both first- and second-line therapies on outcome.
measure: Acute Graft-versus-Host Disease (aGVHD)
time frame: These outcome measures will be assessed at 100 days from transplant
description: cumulative incidence of acute GvHD (grade II-IV)
measure: Chronic Graft-versus-Host Disease (cGVHD)
time frame: These outcome measures will be assessed at 2 year from transplant
description: Cumulative incidence and severity of chronic graft-versus-host disease
measure: Non-Relapse Mortality (NRM)
time frame: These outcome measures will be assessed at 2 year from transplantation
description: Cumulative incidence of Non-Relapse Mortality is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation.
arm group label: Patients with Multiple myeloma
description: Adult with diagnosis of multiple myeloma treated with Allo-HSCT from related - HLA identical or volunteer unrelated donor or haploidentical related donor performed from January 1, 2009 to december 31, 2018
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chiara Nozzoli
role: Principal Investigator
affiliation: Azienda Ospedaliero-Universitaria Careggi, Firenze
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
sharing ipd: No