<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/NCT01675102</url>
  </required_header>
  <id_info>
    <org_study_id>EBMT-42204420</org_study_id>
    <nct_id>NCT01675102</nct_id>
  </id_info>
  <brief_title>Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in 17p- Chronic Lymphocytic Leukemia (CLL)</brief_title>
  <acronym>17p-CLL</acronym>
  <official_title>Allogeneic HSCT in 17p- CLL in First or Second Partial or Complete Remission at Transplant: a Non-interventional Prospective Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>European Society for Blood and Marrow Transplantation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Research Initiative on CLL</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>European Society for Blood and Marrow Transplantation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      17p-/p53-mutated chronic lymphocytic leukemia (CLL) is an orphan disease, accounting for&#xD;
      approximately 5% of newly diagnosed CLL. This subgroup of patients has a very poor outcome&#xD;
      after chemoimmunotherapy. Allogeneic HCT may change the poor prognosis. In a retrospective&#xD;
      EBMT-analysis on 44 patients with advanced 17p-CLL 2-year progression-free survival was 45%&#xD;
      (95% CI, 30% to 60%) after allogeneic HCT (Allogeneic hematopoietic stem-cell transplantation&#xD;
      for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood&#xD;
      and Marrow Transplantation analysis. J Clin Oncol, 2008, 26, 5094-5100).&#xD;
&#xD;
      Referring to these favorable results and small additional series, patients with 17p-CLL&#xD;
      requiring therapy are considered to have an indication for allogeneic transplantation by many&#xD;
      CLL study groups. Several CLL study groups recommend allogeneic HCT in 17p-CLL as part of the&#xD;
      first- or second line treatment.&#xD;
&#xD;
      The aim is to collect additional evidence on allogeneic HCT in 17p-/p53-mutated CLL in first&#xD;
      or second remission by a non-interventional prospective study. Patients shall be registered&#xD;
      prior to HCT at the Leiden Office in order to rule out a reporting bias after&#xD;
      transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective:&#xD;
&#xD;
      The aim is to determine early PFS after allogeneic HCT in first or second remission of&#xD;
      17p-/p53-mutated CLL within an epidemiologic study.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      Neither the decision for allogeneic transplantation nor specific treatment recommendations&#xD;
      for patients with 17p-/p53-mutated CLL are part of the study. Instead, the study protocol&#xD;
      refers to EBMT guidelines. Indications for allogeneic stem cell transplantation in chronic&#xD;
      lymphocytic leukemia: the EBMT transplant consensus. Leukemia 21, 2007, 12-17). Minimal&#xD;
      essential data (MED) A and B, defined by the EBMT, will be collected (www.ebmt.org).&#xD;
&#xD;
      The rate of progression-free survival (PFS) at 1 year after HSCT was selected as primary&#xD;
      endpoint. Death, clinical relapse or progression but not immune manipulations (taper of&#xD;
      immunosuppression, DLI, rituximab) are considered as treatment failure for PFS. Patients&#xD;
      without information on one-year follow up will be considered as having experienced treatment&#xD;
      failure. The rate of PFS at 1 year will be calculated by dividing the number of patients&#xD;
      without treatment failure by the number of patients who met all selection criteria.&#xD;
&#xD;
      For the calculation of the sample size a fixed sample design was selected. The null&#xD;
      hypothesis is that the success-rate for PFS is equal or less than 50%. Referring to the&#xD;
      retrospective EBMT survey, PFS at one year after allogeneic HCT is expected to be 70%.&#xD;
      According to Fleming-A'Hern (1982) the null hypothesis can be rejected with a power of 80%&#xD;
      and an alpha error of 5% if a minimum of 24 out of 37 informative patients did not experience&#xD;
      treatment failure during the first year after allogeneic HCT (Machin et al, Sample Size&#xD;
      Tables for Clinical Studies, Wiley-Blackwell, 3rd edition, 2009). Taking into account a 10%&#xD;
      drop-out rate by violation of inclusion criteria the target number of patients to be included&#xD;
      was set at 41 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 1, 2010</start_date>
  <completion_date type="Actual">December 31, 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival (PFS) rate</measure>
    <time_frame>1 year after HSCT</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of MRD-negative complete remissions</measure>
    <time_frame>1 year after HSCT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival, cumulative incidence of relapse and non-relapse mortality</measure>
    <time_frame>1 year after HSCT</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">41</enrollment>
  <condition>CLL</condition>
  <eligibility>
    <study_pop>
      <textblock>
        eligible patients from EBMT centres&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  17p-/p53-mutated CLL by FISH or sequencing, confirmed by review by an experienced&#xD;
             laboratory&#xD;
&#xD;
          -  first or second partial remission or complete remission at HCT according to the&#xD;
             updated NCI-criteria (Hallek 2008)&#xD;
&#xD;
          -  MRD diagnostic as part of the local standard follow up&#xD;
&#xD;
          -  allogeneic HCT from a matched related or unrelated donor with up to one mismatch&#xD;
             refering to HLA-A, -B, -C and DRB1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ex vivo T-cell depletion&#xD;
&#xD;
          -  in vivo T-cell depletion with alemtuzumab&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Johannes Schetelig, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medizinische Klinik und Poliklinik I, University Hospital Dresden, Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nicolaus Kroeger, MD</last_name>
    <role>Study Chair</role>
    <affiliation>BMT Centre, University Hospital Eppendorf, Hamburg, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rigshospitalitet</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Central Hospital</name>
      <address>
        <city>Helsinki</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik fuer Innere Medzin III</name>
      <address>
        <city>Ulm</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim Sheba Medical Centre</name>
      <address>
        <city>Tel-Hashomer</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Lund</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Hospital</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Finland</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Netherlands</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <last_update_submitted>August 14, 2019</last_update_submitted>
  <last_update_submitted_qc>August 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>del 17p</keyword>
  <keyword>chronic lymphocytic leukemia</keyword>
  <keyword>cll</keyword>
  <keyword>mutation</keyword>
  <keyword>p53</keyword>
  <!-- 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/NCT01675102
org study id: EBMT-42204420
nct id: NCT01675102
lead sponsor: 
collaborator: 
has dmc: No
17p-/p53-mutated chronic lymphocytic leukemia (CLL) is an orphan disease, accounting for
      approximately 5% of newly diagnosed CLL. This subgroup of patients has a very poor outcome
      after chemoimmunotherapy. Allogeneic HCT may change the poor prognosis. In a retrospective
      EBMT-analysis on 44 patients with advanced 17p-CLL 2-year progression-free survival was 45%
      (95% CI, 30% to 60%) after allogeneic HCT (Allogeneic hematopoietic stem-cell transplantation
      for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood
      and Marrow Transplantation analysis. J Clin Oncol, 2008, 26, 5094-5100).

      Referring to these favorable results and small additional series, patients with 17p-CLL
      requiring therapy are considered to have an indication for allogeneic transplantation by many
      CLL study groups. Several CLL study groups recommend allogeneic HCT in 17p-CLL as part of the
      first- or second line treatment.

      The aim is to collect additional evidence on allogeneic HCT in 17p-/p53-mutated CLL in first
      or second remission by a non-interventional prospective study. Patients shall be registered
      prior to HCT at the Leiden Office in order to rule out a reporting bias after
      transplantation.
Objective:

      The aim is to determine early PFS after allogeneic HCT in first or second remission of
      17p-/p53-mutated CLL within an epidemiologic study.

      Methods:

      Neither the decision for allogeneic transplantation nor specific treatment recommendations
      for patients with 17p-/p53-mutated CLL are part of the study. Instead, the study protocol
      refers to EBMT guidelines. Indications for allogeneic stem cell transplantation in chronic
      lymphocytic leukemia: the EBMT transplant consensus. Leukemia 21, 2007, 12-17). Minimal
      essential data (MED) A and B, defined by the EBMT, will be collected (www.ebmt.org).

      The rate of progression-free survival (PFS) at 1 year after HSCT was selected as primary
      endpoint. Death, clinical relapse or progression but not immune manipulations (taper of
      immunosuppression, DLI, rituximab) are considered as treatment failure for PFS. Patients
      without information on one-year follow up will be considered as having experienced treatment
      failure. The rate of PFS at 1 year will be calculated by dividing the number of patients
      without treatment failure by the number of patients who met all selection criteria.

      For the calculation of the sample size a fixed sample design was selected. The null
      hypothesis is that the success-rate for PFS is equal or less than 50%. Referring to the
      retrospective EBMT survey, PFS at one year after allogeneic HCT is expected to be 70%.
      According to Fleming-A'Hern (1982) the null hypothesis can be rejected with a power of 80%
      and an alpha error of 5% if a minimum of 24 out of 37 informative patients did not experience
      treatment failure during the first year after allogeneic HCT (Machin et al, Sample Size
      Tables for Clinical Studies, Wiley-Blackwell, 3rd edition, 2009). Taking into account a 10%
      drop-out rate by violation of inclusion criteria the target number of patients to be included
      was set at 41 patients.
observational model: Cohort
time perspective: Prospective
measure: Progression-free survival (PFS) rate
time frame: 1 year after HSCT
measure: Rate of MRD-negative complete remissions
time frame: 1 year after HSCT
measure: Overall survival, cumulative incidence of relapse and non-relapse mortality
time frame: 1 year after HSCT
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 69 Years
healthy volunteers: No
last name: Johannes Schetelig, MD
role: Principal Investigator
affiliation: Medizinische Klinik und Poliklinik I, University Hospital Dresden, Germany
last name: Nicolaus Kroeger, MD
role: Study Chair
affiliation: BMT Centre, University Hospital Eppendorf, Hamburg, Germany
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Finland
country: Germany
country: Israel
country: Netherlands
country: Sweden
country: United Kingdom
responsible party type: Sponsor