<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/NCT03270748</url>
  </required_header>
  <id_info>
    <org_study_id>GITMO-PHYLOS</org_study_id>
    <nct_id>NCT03270748</nct_id>
  </id_info>
  <brief_title>Post Transplant High-Dose Cy as GvHD Prophylaxis in 1 HLA Mismatched Unrelated HSCT for Myeloid Malignancies</brief_title>
  <acronym>GITMO-PHYLOS</acronym>
  <official_title>Post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 Matched) Unrelated Hemopoietic Stem Cell Transplantation for Myeloid Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gruppo Italiano Trapianto di Midollo Osseo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
      The experimental treatment consists in the application of a therapeutic strategy with post&#xD;
      Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving&#xD;
      1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation&#xD;
      for Myeloid Malignancies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The experimental treatment consists in the application of a therapeutic strategy with post&#xD;
      Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving&#xD;
      1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation&#xD;
      for Myeloid Malignancies Allogeneic hematopoietic stem cell transplantation is a potentially&#xD;
      curative therapy for a variety of hematologic malignancies due to two separate components:&#xD;
      chemo/radiotherapy administered before the transplant (conditioning regimen) and the presence&#xD;
      of immunocompetent cells in the graft, capable of inducing a &quot;graft-versus-malignancy effect&quot;&#xD;
      also known as &quot;GvL&quot; effect. However, this immune-reaction usually carries the risk of&#xD;
      detrimental effects seen as a multi-organ syndrome known as graft-versus-host disease (GvHD),&#xD;
      which remains the most feared complication of Allogeneic hematopoietic stem cell&#xD;
      transplantation. GvHD may be given to disparities between donor and recipient in presence of&#xD;
      gene mismatches in the Major Histocompatibility Complex, also known as Human Leucocyte&#xD;
      Antigen (HLA) system, or in any minor histocompatibility antigen. Thus, GvHD is obviously&#xD;
      more common (and possibly more severe) in patients transplanted from HLA-mismatched donors as&#xD;
      compared with those receiving grafts from HLA-matched donors.&#xD;
&#xD;
      A major limitation of allo-HSCT is the availability of a donor given that only a small&#xD;
      percentage of patients has a HLA identical family donor. For the majority of patients&#xD;
      (approximately 70%) who lack a HLA-identical sibling, alternative donors include HLA-matched&#xD;
      unrelated donors and cord blood units. The chance of identifying a suitable marrow unrelated&#xD;
      donor (MUD) in the international voluntary donor registries is limited by the frequency of a&#xD;
      certain HLA genotype in the general population.&#xD;
&#xD;
      One of the alternative options in such cases is the use of a HLA-mismatched unrelated donor&#xD;
      (MMUD). HLA-mismatching is defined as the presence of unshared antigens/alleles in&#xD;
      recipient-donor pairs for HLA-A, -B, -C or DRB1 loci.&#xD;
&#xD;
      Patients undergoing MUD or MMUD transplants usually receive an intensified three-drug&#xD;
      immunosuppressive regimen: anti-thymocyte globulin in addition to the standard platform of a&#xD;
      calcineurine-inhibitor and an anti-metabolite.&#xD;
&#xD;
      The effect of HLA mismatches on clinical outcomes has been investigated in several studies.&#xD;
      Single HLA mismatches at HLA-A, -B, -C, or -DRB1 locus (7/8 HLA-matched) were associated with&#xD;
      lower overall survival and disease free survival, higher non-relapse mortality, and higher&#xD;
      incidence of acute GvHD as compared with 8/8 HLA-matched pairs.&#xD;
&#xD;
      Many clinical trials suggest that high-dose Cy administrated after allogeneic HSCT didn't&#xD;
      cause prolonged aplasia due toxicity on donor stem cells; could prevent rejection due to&#xD;
      HLA-disparity and could be effective in preventing GvHD, allowing adequate&#xD;
      immune-reconstitution.&#xD;
&#xD;
      With this study the investigators plan to investigate if post-transplant high-dose Cy, with a&#xD;
      calcineurine inhibitor and mycophenolate, could reduce acute GvHD rates and infectious&#xD;
      complications improving clinical outcomes of MMUD transplants in patients with acute myeloid&#xD;
      leukemia and myelodysplastic syndrome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 15, 2020</start_date>
  <completion_date type="Actual">November 20, 2022</completion_date>
  <primary_completion_date type="Actual">November 20, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>incidence of acute GvHD</measure>
    <time_frame>day +100 post-transplant</time_frame>
    <description>cumulative incidence of acute GvHD (grade II-IV) at 100 days post Unrelated Hemopoietic Stem Cell Transplantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>1 year post transplantation</time_frame>
    <description>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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GRFS (GvHD free, relapse free survival)</measure>
    <time_frame>first 12 months after transplantation</time_frame>
    <description>are defined as occurrence of grade III-IV acute GvHD, chronic GvHD requiring systemic immunosuppressive treatment, disease relapse, or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>chronic graft-versus-host disease</measure>
    <time_frame>3 years from transplantation</time_frame>
    <description>Cumulative incidence and severity of chronic graft-versus-host disease (by NIH criteria)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft failure</measure>
    <time_frame>day +100 and 1 year after transplantation</time_frame>
    <description>failure a) Primary graft failure is defined as &lt; 5% donor chimerism. Secondary graft failure (graft rejection) is defined as initial recovery followed by neutropenia with &lt;5% donor chimerism. b) Rate of graft rejection and graft failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Haematopoietic Recovery</measure>
    <time_frame>participants will be followed for the duration of hospital stay, an expected average of 30 days</time_frame>
    <description>Time to reach an absolute neutrophil count &gt; 0.5 109/L from day of HSCT. Neutrophil recovery end-point will be defined as the first of 3 consecutive days with an absolute neutrophil count &gt; 0.5 x109/L. Time to reach platelet engraftment, defined as the number of days after HSCT (Day 0) for patients to maintain an un-transfused platelet count of &gt; 20.0 x 109/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non Relapse Mortality</measure>
    <time_frame>at 100 days, at 180days and at 1 year from transplantation</time_frame>
    <description>The cumulative incidence of Non Relapse Mortality is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse and Residual Disease</measure>
    <time_frame>at 1 year from transplantation</time_frame>
    <description>Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation. For the purpose of this study, relapse is defined by either morphological or cytogenetic evidence of acute myeloid leukemia or myelodisplastic syndrome consistent with pre-transplant features. Molecular relapse will be defined where available as any evidence of a pre-transplant defined abnormality using conventional cytogenetics or FISH techniques or cytofluorimetric analysis or molecular probes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of infectious complications and kinetics of immune-reconstitution</measure>
    <time_frame>one year after transplant</time_frame>
    <description>the rate of proven and probable invasive fungal infections and viral reactivation/disease (CMV, HHV6,Adenovirus, EBV). Immune-reconstitution will be evaluated with lymphocyte sub-populations counts (CD3+, CD4+, CD8+, CD16+, CD20+) and IgG, IgA, IgM titer</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Myeloid Malignancies</condition>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental: Experimental The experimental consists in the application of a therapeutic strategy: post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation for Myeloid Malignancies Therapeutic intervention, namely conditioning regimen and GVHD prophylaxis, are based on standard current regimens: Busulfan 0,8 mg/kg 4 times per day during 2 h infusions for 4 consecutive days (from day -6 through day -3) Fludarabine 40 mg/m2 per day for 4 days (from day -6 through day -3); GvHD prophylaxis: Cyclosporine or Tacrolimus beginning day+5 up to at least 100 days. Micofenolate 15mg/kg twice a day from day +5 to +35.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GvHD prophylaxis</intervention_name>
    <description>Cyclophosphamide 50 mg/kg intravenously day+3 and +4 (total dose:100 mg/kg).</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Acute myeloid leukemia in complete remission Myelodysplastic syndrome Indication for&#xD;
        allo-HCT No available HLA identical sibling donor or HLA matched unrelated donor Activation&#xD;
        of an alternative donor search Presence of a 1 antigen/allele mismatched (7/8 HLA matched)&#xD;
        unrelated donor ECOG performance status &lt;2 Written and signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        left ventricular ejection fraction &lt; 40% FEV1, FVC, DLCO &lt;50% of predicted LFT &gt; 5 times&#xD;
        the upper limit of normal creatinine clearance &lt; 40 ml/min Previous allogeneic Hemopoietic&#xD;
        Stem Cell Transplantation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Annamaria Raiola, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale Policlinico San Martino-IST</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Azienda Ospedaliera SS Antonio e Biagio</name>
      <address>
        <city>Alessandria</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedali Riuniti</name>
      <address>
        <city>Ancona</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Moscati</name>
      <address>
        <city>Avellino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico di Bari-Ematologia con trapianti</name>
      <address>
        <city>Bari</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Divisione di Ematologia - Ospedali Papa Giovanni XXIII</name>
      <address>
        <city>Bergamo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Orsola</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Regionale Generale- Divisione Ematologia</name>
      <address>
        <city>Bolzano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST Spedali Civili</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Binaghi</name>
      <address>
        <city>Cagliari</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle</name>
      <address>
        <city>Cuneo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza</name>
      <address>
        <city>Foggia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU-IRCCS San Martino-IST</name>
      <address>
        <city>Genova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osp. Card. Panico</name>
      <address>
        <city>Lecce</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU Integrata</name>
      <address>
        <city>Mestre</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Niguarda Ca' Grande</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -</name>
      <address>
        <city>Modena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST Ospedale S. Gerardo de' i Tintori - Università degli Studi di Milano</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. Policlinico Federico II</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda ospedaliera Universitaria di Parma</name>
      <address>
        <city>Parma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS San Matteo</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale G. Da Saliceto di Piacenza</name>
      <address>
        <city>Piacenza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli</name>
      <address>
        <city>Reggio Calabria</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. San Camillo Forlanini</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Umberto I</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Az. Ospedaliera Universitaria Senese - Divisione Ematologia e Trapianti</name>
      <address>
        <city>Siena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Moscati</name>
      <address>
        <city>Taranto</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. Citta della Salute e della Scienza</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Gonzaga</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Santa Maria della Misericordia</name>
      <address>
        <city>Udine</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Bortolo-Divisione Ematologia</name>
      <address>
        <city>Vicenza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</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 hematopoietic stem cell transplantation</keyword>
  <keyword>acute graft-versus-host disease</keyword>
  <keyword>Unrelated donors</keyword>
  <keyword>Post-transplant cyclophosphamide</keyword>
  <keyword>Myeloid Malignancies</keyword>
  <keyword>unrelated hematopoietic cell transplantation</keyword>
  <keyword>GITMO</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT03270748
org study id: GITMO-PHYLOS
nct id: NCT03270748
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The experimental treatment consists in the application of a therapeutic strategy with post
      Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving
      1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation
      for Myeloid Malignancies.
The experimental treatment consists in the application of a therapeutic strategy with post
      Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving
      1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation
      for Myeloid Malignancies Allogeneic hematopoietic stem cell transplantation is a potentially
      curative therapy for a variety of hematologic malignancies due to two separate components:
      chemo/radiotherapy administered before the transplant (conditioning regimen) and the presence
      of immunocompetent cells in the graft, capable of inducing a "graft-versus-malignancy effect"
      also known as "GvL" effect. However, this immune-reaction usually carries the risk of
      detrimental effects seen as a multi-organ syndrome known as graft-versus-host disease (GvHD),
      which remains the most feared complication of Allogeneic hematopoietic stem cell
      transplantation. GvHD may be given to disparities between donor and recipient in presence of
      gene mismatches in the Major Histocompatibility Complex, also known as Human Leucocyte
      Antigen (HLA) system, or in any minor histocompatibility antigen. Thus, GvHD is obviously
      more common (and possibly more severe) in patients transplanted from HLA-mismatched donors as
      compared with those receiving grafts from HLA-matched donors.

      A major limitation of allo-HSCT is the availability of a donor given that only a small
      percentage of patients has a HLA identical family donor. For the majority of patients
      (approximately 70%) who lack a HLA-identical sibling, alternative donors include HLA-matched
      unrelated donors and cord blood units. The chance of identifying a suitable marrow unrelated
      donor (MUD) in the international voluntary donor registries is limited by the frequency of a
      certain HLA genotype in the general population.

      One of the alternative options in such cases is the use of a HLA-mismatched unrelated donor
      (MMUD). HLA-mismatching is defined as the presence of unshared antigens/alleles in
      recipient-donor pairs for HLA-A, -B, -C or DRB1 loci.

      Patients undergoing MUD or MMUD transplants usually receive an intensified three-drug
      immunosuppressive regimen: anti-thymocyte globulin in addition to the standard platform of a
      calcineurine-inhibitor and an anti-metabolite.

      The effect of HLA mismatches on clinical outcomes has been investigated in several studies.
      Single HLA mismatches at HLA-A, -B, -C, or -DRB1 locus (7/8 HLA-matched) were associated with
      lower overall survival and disease free survival, higher non-relapse mortality, and higher
      incidence of acute GvHD as compared with 8/8 HLA-matched pairs.

      Many clinical trials suggest that high-dose Cy administrated after allogeneic HSCT didn't
      cause prolonged aplasia due toxicity on donor stem cells; could prevent rejection due to
      HLA-disparity and could be effective in preventing GvHD, allowing adequate
      immune-reconstitution.

      With this study the investigators plan to investigate if post-transplant high-dose Cy, with a
      calcineurine inhibitor and mycophenolate, could reduce acute GvHD rates and infectious
      complications improving clinical outcomes of MMUD transplants in patients with acute myeloid
      leukemia and myelodysplastic syndrome.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: incidence of acute GvHD
time frame: day +100 post-transplant
description: cumulative incidence of acute GvHD (grade II-IV) at 100 days post Unrelated Hemopoietic Stem Cell Transplantation
measure: Overall survival
time frame: 1 year post transplantation
description: 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: GRFS (GvHD free, relapse free survival)
time frame: first 12 months after transplantation
description: are defined as occurrence of grade III-IV acute GvHD, chronic GvHD requiring systemic immunosuppressive treatment, disease relapse, or death from any cause
measure: chronic graft-versus-host disease
time frame: 3 years from transplantation
description: Cumulative incidence and severity of chronic graft-versus-host disease (by NIH criteria)
measure: Graft failure
time frame: day +100 and 1 year after transplantation
description: failure a) Primary graft failure is defined as < 5% donor chimerism. Secondary graft failure (graft rejection) is defined as initial recovery followed by neutropenia with <5% donor chimerism. b) Rate of graft rejection and graft failure
measure: Haematopoietic Recovery
time frame: participants will be followed for the duration of hospital stay, an expected average of 30 days
description: Time to reach an absolute neutrophil count > 0.5 109/L from day of HSCT. Neutrophil recovery end-point will be defined as the first of 3 consecutive days with an absolute neutrophil count > 0.5 x109/L. Time to reach platelet engraftment, defined as the number of days after HSCT (Day 0) for patients to maintain an un-transfused platelet count of > 20.0 x 109/L.
measure: Non Relapse Mortality
time frame: at 100 days, at 180days and at 1 year from transplantation
description: The cumulative incidence of Non Relapse Mortality is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence
measure: Relapse and Residual Disease
time frame: at 1 year from transplantation
description: Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation. For the purpose of this study, relapse is defined by either morphological or cytogenetic evidence of acute myeloid leukemia or myelodisplastic syndrome consistent with pre-transplant features. Molecular relapse will be defined where available as any evidence of a pre-transplant defined abnormality using conventional cytogenetics or FISH techniques or cytofluorimetric analysis or molecular probes
measure: Incidence of infectious complications and kinetics of immune-reconstitution
time frame: one year after transplant
description: the rate of proven and probable invasive fungal infections and viral reactivation/disease (CMV, HHV6,Adenovirus, EBV). Immune-reconstitution will be evaluated with lymphocyte sub-populations counts (CD3+, CD4+, CD8+, CD16+, CD20+) and IgG, IgA, IgM titer
arm group label: Experimental
arm group type: Experimental
description: Experimental: Experimental The experimental consists in the application of a therapeutic strategy: post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation for Myeloid Malignancies Therapeutic intervention, namely conditioning regimen and GVHD prophylaxis, are based on standard current regimens: Busulfan 0,8 mg/kg 4 times per day during 2 h infusions for 4 consecutive days (from day -6 through day -3) Fludarabine 40 mg/m2 per day for 4 days (from day -6 through day -3); GvHD prophylaxis: Cyclosporine or Tacrolimus beginning day+5 up to at least 100 days. Micofenolate 15mg/kg twice a day from day +5 to +35.
intervention type: Drug
intervention name: GvHD prophylaxis
description: Cyclophosphamide 50 mg/kg intravenously day+3 and +4 (total dose:100 mg/kg).
arm group label: Experimental
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Annamaria Raiola, MD
role: Principal Investigator
affiliation: Ospedale Policlinico San Martino-IST
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country: Italy
responsible party type: Sponsor
mesh term: Neoplasms