<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/NCT03818334</url>
  </required_header>
  <id_info>
    <org_study_id>SGPP 3549-18</org_study_id>
    <nct_id>NCT03818334</nct_id>
  </id_info>
  <brief_title>Post Transplant Cyclophosphamide in Matched Unrelated Donor Stem Cell Transplantation for Hematological Malignancies</brief_title>
  <official_title>Use of Post Transplant Cyclophosphamide as Graft Versus Host Disease Prophylaxis in Matched Unrelated Donor Stem Cell Transplantation for Hematological Malignancies, a Prospective Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Israelita Albert Einstein</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Israelita Albert Einstein</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate the clinical efficacy of cyclophosphamide in patients receiving a&#xD;
      bone marrow graft from a matched unrelated donor in overall survival, progression free&#xD;
      survival and cumulative incidence of acute and chronic GvHD. Thirty patients will receive&#xD;
      cyclophosphamide while twenty patients will receive antihuman T-lymphocyte immune globulin&#xD;
      (ATG).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 6, 2018</start_date>
  <completion_date type="Anticipated">November 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>4 years</time_frame>
    <description>Time to last follow-up or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>4 years</time_frame>
    <description>Time until last follow-up, death or disease relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Graft Versus Host Disease</measure>
    <time_frame>4 years</time_frame>
    <description>Time until acute GvHD development</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic Graft Versus Host Disease</measure>
    <time_frame>4 years</time_frame>
    <description>Time until chronic GvHD development</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Related Mortality</measure>
    <time_frame>4 years</time_frame>
    <description>Time until death related to HSCT complications</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Graft Failure Incidence</measure>
    <time_frame>2 years</time_frame>
    <description>ANC &lt; 500/microL after 42 days after graft infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Time Until Neutrophil Engraftment</measure>
    <time_frame>2 years</time_frame>
    <description>Time to ANC &gt; 500/microL for three consecutive days</description>
  </other_outcome>
  <other_outcome>
    <measure>Time Until Platelet Engraftment</measure>
    <time_frame>2 years</time_frame>
    <description>Time to platelet count &gt; 50,000/microL, without transfusion in the last 7 days</description>
  </other_outcome>
  <other_outcome>
    <measure>Immunological Reconstitution</measure>
    <time_frame>Days +60, +100 and +180</time_frame>
    <description>Total lymphocyte count as well as its subsets (CD4, CD8, CD19, CD56)</description>
  </other_outcome>
  <other_outcome>
    <measure>Days hospitalized</measure>
    <time_frame>First 100 days after graft infusion</time_frame>
    <description>Days admitted to the hospital</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Bone Marrow Transplant Complications</condition>
  <condition>Graft Versus Host Disease</condition>
  <condition>Infection Viral</condition>
  <condition>Engraft Failure</condition>
  <condition>Immunologic Suppression</condition>
  <arm_group>
    <arm_group_label>Post Cyclophosphamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cyclophosphamide 50 mg/Kg on days +3 and +4 AND Calcineurin Inhibitor from day +5 AND Mycofenolate Mofetil from day +5 until day +35</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Thymoglobulin (ATG)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Thymoglobulin (ATG) total dose 5 mg/Kg from day -4 until day -1 AND Calcineurin Inhibitor from day +5 AND Methotrexate on days +1, +3, +6 and +11</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide 1000 mg/flask</description>
    <arm_group_label>Post Cyclophosphamide</arm_group_label>
    <other_name>Cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ATG</intervention_name>
    <description>Antihuman T-Lymphocyte Immune Globulin 25 mg/flask</description>
    <arm_group_label>Thymoglobulin (ATG)</arm_group_label>
    <other_name>Thymoglobulin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and Women of Any Age&#xD;
&#xD;
          -  Indication for an HSCT without matched sibling donor&#xD;
&#xD;
          -  Have a matched unrelated donor (HLA 10 x 10 or 9 x 10)&#xD;
&#xD;
          -  Hematological malignancy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute leukemias not in complete response (that is &gt; 5% blast in the bone marrow)&#xD;
&#xD;
          -  Chemorefractory lymphoproliferative disease&#xD;
&#xD;
          -  Active uncontrolled infection&#xD;
&#xD;
          -  HCT-CI &gt; 3&#xD;
&#xD;
          -  Severe organic disfunction (heart ejection fraction &lt; 45%, glomerular filtration rate&#xD;
             &lt; 50 mL.hour, pulmonary DLCO &lt; 50%)&#xD;
&#xD;
          -  Previous allogeneic bone marrow transplantation&#xD;
&#xD;
          -  Contraindication to cyclophosphamide or ATG&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andreza A Feitosa Ribeiro, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Israelita Albert Einstein</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nelson Hamerschlak, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Israelita Albert Einstein</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Andreza A Feitosa Ribeiro</last_name>
    <phone>+5511992512523</phone>
    <email>andreza.ribeiro@einstein.br</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospita Israelita Albert Eintein</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>05652-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mirele Santos</last_name>
      <phone>+112151-0305</phone>
      <email>mirele.santos@einstein.br</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Finke J, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, Volin L, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhauser M, Einsele H, Bertz H, Grishina O, Socie G; ATG-Fresenius Trial Group. Prognostic factors affecting outcome after allogeneic transplantation for hematological malignancies from unrelated donors: results from a randomized trial. Biol Blood Marrow Transplant. 2012 Nov;18(11):1716-26. doi: 10.1016/j.bbmt.2012.06.001. Epub 2012 Jun 17.</citation>
    <PMID>22713691</PMID>
  </reference>
  <reference>
    <citation>Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Sacchi N, van Lint MT, Bosi A; Gruppo Italiano Trapianti Midollo Osseo (GITMO). Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant. 2006 May;12(5):560-5. doi: 10.1016/j.bbmt.2005.12.034.</citation>
    <PMID>16635791</PMID>
  </reference>
  <reference>
    <citation>Devillier R, Labopin M, Chevallier P, Ledoux MP, Socie G, Huynh A, Bourhis JH, Cahn JY, Roth-Guepin G, Mufti G, Desmier D, Michallet M, Fegueux N, Ciceri F, Baron F, Blaise D, Nagler A, Mohty M. Impact of antithymocyte globulin doses in reduced intensity conditioning before allogeneic transplantation from matched sibling donor for patients with acute myeloid leukemia: a report from the acute leukemia working party of European group of Bone Marrow Transplantation. Bone Marrow Transplant. 2018 Apr;53(4):431-437. doi: 10.1038/s41409-017-0043-y. Epub 2018 Jan 12.</citation>
    <PMID>29330391</PMID>
  </reference>
  <reference>
    <citation>Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J. Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood. 2012 Apr 26;119(17):3908-16. doi: 10.1182/blood-2011-09-381699. Epub 2012 Feb 10.</citation>
    <PMID>22327226</PMID>
  </reference>
  <reference>
    <citation>Mehta RS, Saliba RM, Chen J, Rondon G, Hammerstrom AE, Alousi A, Qazilbash M, Bashir Q, Ahmed S, Popat U, Hosing C, Khouri I, Shpall EJ, Champlin RE, Ciurea SO. Post-transplantation cyclophosphamide versus conventional graft-versus-host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation. Br J Haematol. 2016 May;173(3):444-55. doi: 10.1111/bjh.13977. Epub 2016 Mar 7.</citation>
    <PMID>26947769</PMID>
  </reference>
  <reference>
    <citation>Rashidi A, Slade M, DiPersio JF, Westervelt P, Vij R, Romee R. Post-transplant high-dose cyclophosphamide after HLA-matched vs haploidentical hematopoietic cell transplantation for AML. Bone Marrow Transplant. 2016 Dec;51(12):1561-1564. doi: 10.1038/bmt.2016.217. Epub 2016 Aug 15.</citation>
    <PMID>27526282</PMID>
  </reference>
  <reference>
    <citation>Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, Slesarchuk OA, Bondarenko SN, Afanasyev BV. Graft-versus-Host Disease Prophylaxis in Unrelated Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil. Biol Blood Marrow Transplant. 2016 Jun;22(6):1037-1042. doi: 10.1016/j.bbmt.2016.03.004. Epub 2016 Mar 10.</citation>
    <PMID>26970381</PMID>
  </reference>
  <reference>
    <citation>Kanakry CG, Bolanos-Meade J, Kasamon YL, Zahurak M, Durakovic N, Furlong T, Mielcarek M, Medeot M, Gojo I, Smith BD, Kanakry JA, Borrello IM, Brodsky RA, Gladstone DE, Huff CA, Matsui WH, Swinnen LJ, Cooke KR, Ambinder RF, Fuchs EJ, de Lima MJ, Andersson BS, Varadhan R, O'Donnell PV, Jones RJ, Luznik L. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide. Blood. 2017 Mar 9;129(10):1389-1393. doi: 10.1182/blood-2016-09-737825. Epub 2017 Jan 3.</citation>
    <PMID>28049637</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>January 31, 2019</last_update_submitted>
  <last_update_submitted_qc>January 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Israelita Albert Einstein</investigator_affiliation>
    <investigator_full_name>Andreza Alice Feitosa Ribeiro</investigator_full_name>
    <investigator_title>Assistant Physician specialist in Hematopoietic Stem Transplantation, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Bone Marrow Transplantation</keyword>
  <keyword>Hematological Malignancies</keyword>
  <keyword>Post-Cy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Thymoglobulin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03818334
org study id: SGPP 3549-18
nct id: NCT03818334
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate the clinical efficacy of cyclophosphamide in patients receiving a
      bone marrow graft from a matched unrelated donor in overall survival, progression free
      survival and cumulative incidence of acute and chronic GvHD. Thirty patients will receive
      cyclophosphamide while twenty patients will receive antihuman T-lymphocyte immune globulin
      (ATG).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Overall Survival
time frame: 4 years
description: Time to last follow-up or death
measure: Progression free survival
time frame: 4 years
description: Time until last follow-up, death or disease relapse
measure: Acute Graft Versus Host Disease
time frame: 4 years
description: Time until acute GvHD development
measure: Chronic Graft Versus Host Disease
time frame: 4 years
description: Time until chronic GvHD development
measure: Treatment Related Mortality
time frame: 4 years
description: Time until death related to HSCT complications
measure: Graft Failure Incidence
time frame: 2 years
description: ANC < 500/microL after 42 days after graft infusion
measure: Time Until Neutrophil Engraftment
time frame: 2 years
description: Time to ANC > 500/microL for three consecutive days
measure: Time Until Platelet Engraftment
time frame: 2 years
description: Time to platelet count > 50,000/microL, without transfusion in the last 7 days
measure: Immunological Reconstitution
time frame: Days +60, +100 and +180
description: Total lymphocyte count as well as its subsets (CD4, CD8, CD19, CD56)
measure: Days hospitalized
time frame: First 100 days after graft infusion
description: Days admitted to the hospital
arm group label: Post Cyclophosphamide
arm group type: Experimental
description: Cyclophosphamide 50 mg/Kg on days +3 and +4 AND Calcineurin Inhibitor from day +5 AND Mycofenolate Mofetil from day +5 until day +35
arm group label: Thymoglobulin (ATG)
arm group type: Active Comparator
description: Thymoglobulin (ATG) total dose 5 mg/Kg from day -4 until day -1 AND Calcineurin Inhibitor from day +5 AND Methotrexate on days +1, +3, +6 and +11
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide 1000 mg/flask
arm group label: Post Cyclophosphamide
other name: Cytoxan
intervention type: Drug
intervention name: ATG
description: Antihuman T-Lymphocyte Immune Globulin 25 mg/flask
arm group label: Thymoglobulin (ATG)
other name: Thymoglobulin
criteria: 
gender: All
minimum age: 1 Year
maximum age: 75 Years
healthy volunteers: No
last name: Andreza A Feitosa Ribeiro, PhD
role: Principal Investigator
affiliation: Hospital Israelita Albert Einstein
last name: Nelson Hamerschlak, PhD
role: Study Chair
affiliation: Hospital Israelita Albert Einstein
last name: Andreza A Feitosa Ribeiro
phone: +5511992512523
email: andreza.ribeiro@einstein.br
facility: 
status: Recruiting
contact: 
country: Brazil
citation: Finke J, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, Volin L, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhauser M, Einsele H, Bertz H, Grishina O, Socie G; ATG-Fresenius Trial Group. Prognostic factors affecting outcome after allogeneic transplantation for hematological malignancies from unrelated donors: results from a randomized trial. Biol Blood Marrow Transplant. 2012 Nov;18(11):1716-26. doi: 10.1016/j.bbmt.2012.06.001. Epub 2012 Jun 17.
PMID: 22713691
citation: Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Sacchi N, van Lint MT, Bosi A; Gruppo Italiano Trapianti Midollo Osseo (GITMO). Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant. 2006 May;12(5):560-5. doi: 10.1016/j.bbmt.2005.12.034.
PMID: 16635791
citation: Devillier R, Labopin M, Chevallier P, Ledoux MP, Socie G, Huynh A, Bourhis JH, Cahn JY, Roth-Guepin G, Mufti G, Desmier D, Michallet M, Fegueux N, Ciceri F, Baron F, Blaise D, Nagler A, Mohty M. Impact of antithymocyte globulin doses in reduced intensity conditioning before allogeneic transplantation from matched sibling donor for patients with acute myeloid leukemia: a report from the acute leukemia working party of European group of Bone Marrow Transplantation. Bone Marrow Transplant. 2018 Apr;53(4):431-437. doi: 10.1038/s41409-017-0043-y. Epub 2018 Jan 12.
PMID: 29330391
citation: Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J. Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood. 2012 Apr 26;119(17):3908-16. doi: 10.1182/blood-2011-09-381699. Epub 2012 Feb 10.
PMID: 22327226
citation: Mehta RS, Saliba RM, Chen J, Rondon G, Hammerstrom AE, Alousi A, Qazilbash M, Bashir Q, Ahmed S, Popat U, Hosing C, Khouri I, Shpall EJ, Champlin RE, Ciurea SO. Post-transplantation cyclophosphamide versus conventional graft-versus-host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation. Br J Haematol. 2016 May;173(3):444-55. doi: 10.1111/bjh.13977. Epub 2016 Mar 7.
PMID: 26947769
citation: Rashidi A, Slade M, DiPersio JF, Westervelt P, Vij R, Romee R. Post-transplant high-dose cyclophosphamide after HLA-matched vs haploidentical hematopoietic cell transplantation for AML. Bone Marrow Transplant. 2016 Dec;51(12):1561-1564. doi: 10.1038/bmt.2016.217. Epub 2016 Aug 15.
PMID: 27526282
citation: Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, Slesarchuk OA, Bondarenko SN, Afanasyev BV. Graft-versus-Host Disease Prophylaxis in Unrelated Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil. Biol Blood Marrow Transplant. 2016 Jun;22(6):1037-1042. doi: 10.1016/j.bbmt.2016.03.004. Epub 2016 Mar 10.
PMID: 26970381
citation: Kanakry CG, Bolanos-Meade J, Kasamon YL, Zahurak M, Durakovic N, Furlong T, Mielcarek M, Medeot M, Gojo I, Smith BD, Kanakry JA, Borrello IM, Brodsky RA, Gladstone DE, Huff CA, Matsui WH, Swinnen LJ, Cooke KR, Ambinder RF, Fuchs EJ, de Lima MJ, Andersson BS, Varadhan R, O'Donnell PV, Jones RJ, Luznik L. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide. Blood. 2017 Mar 9;129(10):1389-1393. doi: 10.1182/blood-2016-09-737825. Epub 2017 Jan 3.
PMID: 28049637
responsible party type: Principal Investigator
investigator affiliation: Hospital Israelita Albert Einstein
investigator full name: Andreza Alice Feitosa Ribeiro
investigator title: Assistant Physician specialist in Hematopoietic Stem Transplantation, Principal Investigator
mesh term: Virus Diseases
mesh term: Neoplasms
mesh term: Hematologic Neoplasms
mesh term: Graft vs Host Disease
mesh term: Cyclophosphamide
mesh term: Thymoglobulin
sharing ipd: Undecided