<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/NCT02258490</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00051037</org_study_id>
    <secondary_id>EPIC-HPC001</secondary_id>
    <nct_id>NCT02258490</nct_id>
  </id_info>
  <brief_title>Expanded Use of G-CSF Mobilized Donor CD34+ Selected Cells for Allogeneic Transplantation</brief_title>
  <official_title>Expanded Use of G-CSF Mobilized Donor CD34+ Selected Cells for Allogeneic Transplantation to Recipients With Limited Donor Engraftment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Emory University</source>
  <brief_summary>
    <textblock>
      Allogeneic hematopoietic stem cell transplantation (HSCT) is an established form of treatment&#xD;
      for hematological abnormalities. Poor graft function, occurs when there poor donor&#xD;
      engraftment. A second infusion of unselected donor hematopoietic stem cells (HSC) can result&#xD;
      in improvement, but can potentially increase the incidence of graft versus host disease.&#xD;
      Cluster of differentiation 34+ (CD34+) selected stem cells depleted of T-cells is an&#xD;
      attractive alternative for treatment of poor graft function as it may be associated with less&#xD;
      Graft versus Host Disease (GVHD) and enhanced count recovery. The investigators are using the&#xD;
      Miltenyi CliniMACS device and CD34 cell selection reagents for the preparation of allogeneic&#xD;
      hematopoietic progenitor cell (HPC) transplants for patients who have had prior stem cell&#xD;
      transplants and require a stem cell &quot;boost&quot; from the original donor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-arm, open label, single institution, compassionate study which will enroll&#xD;
      patients who are marginally engrafted and transfusion and/or growth factors dependent after&#xD;
      allogeneic hematopoietic stem cell transplant (HSCT) regardless of the underlying disease for&#xD;
      which the transplant was performed. Study subjects will receive a &quot;booster&quot; infusion of CD34+&#xD;
      cell selected and T-cell depleted G-CSF mobilized apheresis product from the original stem&#xD;
      cell donor in order to improve engraftment. The &quot;booster&quot; infusion will be administered&#xD;
      without prior conditioning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>No longer available</overall_status>
  <study_type>Expanded Access</study_type>
  <has_expanded_access>No</has_expanded_access>
  <condition>Chronic Myeloid Leukemia</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>G-CSF mobilized CD34+ selected cells for transplantation</intervention_name>
    <description>After screening and enrollment, donor will receive mobilization therapy with G-CSF (10 ug/Kg S/C daily x5-6 days) using standard National Marrow Donor Program guidelines. CD34+ cell selection will be performed according to procedures given in CliniMACS Operating Manual and institutional Standard Operating Procedures. If storage after CD34+ selection is necessary, product will be kept in a monitored refrigerator. During storage, leukocyte concentration should not exceed 2 x 108 cells/ml using platelet poor plasma to adjust cell concentration. If donor's plasma is not available, CliniMACS buffer will be used. Cell processing will be performed by personnel trained by Miltenyi on CliniMACS system prior to initiation of clinical product selection. After tests are performed and product passes release criteria, patient will receive final product. No conditioning regimen will be administered prior to cell infusion.</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Donor Inclusion Criteria:&#xD;
&#xD;
          -  Donors must be eligible and approved for a hematopoietic stem cell graft according to&#xD;
             institutional criteria (related donor) or NMDP criteria (volunteer unrelated donor)&#xD;
&#xD;
          -  Donors must be ≥ 17 years old and ≤ 75 years old&#xD;
&#xD;
          -  Donors must be agreeable to receive G-CSF for CD34 cell mobilization and undergo&#xD;
             apheresis for the second donation of peripheral blood mononuclear cells (PBMC)&#xD;
&#xD;
          -  Donor must have adequate peripheral venous catheter access for apheresis or must agree&#xD;
             to placement of a central catheter&#xD;
&#xD;
          -  The following laboratory tests/evaluations will be performed for all donors registered&#xD;
             in the study. Additional evaluations/studies may also be performed by the site as&#xD;
             dictated by the donor's clinical situation or standard practice for monitoring normal&#xD;
             donors&#xD;
&#xD;
               -  History and physical examination&#xD;
&#xD;
               -  Automated complete blood count (WBC, red blood cells [RBC], hematocrit,&#xD;
                  hemoglobin) with differential and platelet counts&#xD;
&#xD;
               -  Serum chemistries panel including electrolytes, glucose, blood urea nitrogen&#xD;
                  (BUN), alanine aminotransferase (ALT), creatinine, bilirubin, alkaline&#xD;
                  phosphatase, lactate dehydrogenase (LDH) and albumin. Electrolytes to include&#xD;
                  sodium, potassium, chloride, carbon dioxide, calcium and magnesium.&#xD;
&#xD;
               -  Infections disease titers by FDA licensed tests for:&#xD;
&#xD;
                    -  Cytomegalovirus (CMV) antibody&#xD;
&#xD;
                    -  Hepatitis panel (Hepatitis B including HBsAg, HBcAb [immunoglobulin M {IgM}&#xD;
                       and immunoglobulin G {IgG}]; hepatitis C antibody)&#xD;
&#xD;
                    -  HIV 1+2 antibodies&#xD;
&#xD;
                    -  Hepatitis C virus (HCV) antibodies&#xD;
&#xD;
                    -  Human T-lymphotropic virus (HTLV) I/II antibodies&#xD;
&#xD;
                    -  Rapid plasmin reagin (RPR)&#xD;
&#xD;
                    -  HIV-1 nucleic acid amplification test (NAT)&#xD;
&#xD;
                    -  HCV NAT&#xD;
&#xD;
                    -  West Nile virus (WNV)&#xD;
&#xD;
                    -  These tests will be obtained, and reported to Emory, within 30 days prior to&#xD;
                       collection of the CD34+ cell product.&#xD;
&#xD;
        Recipient Inclusion Criteria:&#xD;
&#xD;
          -  Only patients who are experiencing life-threatening hematological insufficiency,&#xD;
             following an allogeneic hematopoietic stem cell transplant will be enrolled into this&#xD;
             study&#xD;
&#xD;
          -  Patient must be age &gt; 17&#xD;
&#xD;
          -  Must have ≥ 90% donor cells in the unfractionated peripheral blood based on either XY&#xD;
             fluorescence in situ hybridization (FISH) or standard short tandem repeats (STR)&#xD;
&#xD;
          -  More than 60 days post allogeneic stem cell transplantation and no reversible etiology&#xD;
             found after an allogeneic stem cell transplantation&#xD;
&#xD;
          -  Must meet one of the following criteria:&#xD;
&#xD;
               -  Platelets &lt; 20,000/μl, absolute neutrophil count (ANC) &lt; 500/μl or&#xD;
&#xD;
               -  Transfusion dependent for at least one cell line and/or&#xD;
&#xD;
               -  On growth factor support (G-CSF) without adequate response for 30 days&#xD;
&#xD;
          -  The original HSCT donor must be available, willing, and medically able to undergo&#xD;
             G-CSF mobilization and the apheresis procedures&#xD;
&#xD;
          -  Patients must have non-immune mediated graft dysfunction&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>17 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Edmund Waller, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Davies SM, Weisdorf DJ, Haake RJ, Kersey JH, McGlave PB, Ramsay NK, Blazar BR. Second infusion of bone marrow for treatment of graft failure after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1994 Jul;14(1):73-7.</citation>
    <PMID>7951123</PMID>
  </reference>
  <reference>
    <citation>Elmaagacli AH, Peceny R, Steckel N, Trenschel R, Ottinger H, Grosse-Wilde H, Schaefer UW, Beelen DW. Outcome of transplantation of highly purified peripheral blood CD34+ cells with T-cell add-back compared with unmanipulated bone marrow or peripheral blood stem cells from HLA-identical sibling donors in patients with first chronic phase chronic myeloid leukemia. Blood. 2003 Jan 15;101(2):446-53. doi: 10.1182/blood-2002-05-1615. Epub 2002 Sep 12.</citation>
    <PMID>12393406</PMID>
  </reference>
  <reference>
    <citation>Lang P, Handgretinger R, Niethammer D, Schlegel PG, Schumm M, Greil J, Bader P, Engel C, Scheel-Walter H, Eyrich M, Klingebiel T. Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood. 2003 Feb 15;101(4):1630-6. doi: 10.1182/blood-2002-04-1203. Epub 2002 Oct 10.</citation>
    <PMID>12393439</PMID>
  </reference>
  <reference>
    <citation>Urbano-Ispizua A, Brunet S, Solano C, Moraleda JM, Rovira M, Zuazu J, de La Rubia J, Bargay J, Caballero D, Diez-Martin JL, Ojeda E, Perez de Oteiza JP, Ferra C, Espigado I, Alegre A, de La Serna J, Torres P, Riu C, Odriozola J, Rozman C, Sierra J, Garcia-Conde J, Montserrat E; Spanish Group of Allo-PBT. Allogeneic transplantation of CD34+-selected cells from peripheral blood in patients with myeloid malignancies in early phase: a case control comparison with unmodified peripheral blood transplantation. Bone Marrow Transplant. 2001 Aug;28(4):349-54. doi: 10.1038/sj.bmt.1703154.</citation>
    <PMID>11571506</PMID>
  </reference>
  <reference>
    <citation>Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, Bregante S, Lamparelli T, Tedone E, Oneto R, Frassoni F, Van Lint MT, Pogliani E, Bacigalupo A. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. 2006 Jul;91(7):935-40.</citation>
    <PMID>16818281</PMID>
  </reference>
  <reference>
    <citation>Tabilio A, Falzetti F, Zei T, De Ioanni M, Bonifacio E, Battelli F, Iacucci Ostini R, Ballanti S, Cimminiello M, Capponi M, Silvani C, Minelli O, Fettucciari K, Marconi P, Rosati E, Santucci A, Di Ianni M, Aversa F, Martelli MF. Graft engineering for allogeneic haploidentical stem cell transplantation. Blood Cells Mol Dis. 2004 Nov-Dec;33(3):274-80. doi: 10.1016/j.bcmd.2004.08.016.</citation>
    <PMID>15528144</PMID>
  </reference>
  <reference>
    <citation>Markiewicz M, Holowiecki J, Wojnar J, Krawczyk-Kulis M, Jagoda K, Giebel S, Kruzel T. Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients. Transplant Proc. 2004 Dec;36(10):3194-9. doi: 10.1016/j.transproceed.2004.09.052.</citation>
    <PMID>15686727</PMID>
  </reference>
  <reference>
    <citation>Oyekunle A, Koehl U, Schieder H, Ayuk F, Renges H, Fehse N, Zabelina T, Fehse B, Klingebiel T, Sputtek A, Zander A, Kroger N. CD34(+)-selected stem cell boost for delayed or insufficient engraftment after allogeneic stem cell transplantation. Cytotherapy. 2006;8(4):375-80. doi: 10.1080/14653240600735784.</citation>
    <PMID>16923613</PMID>
  </reference>
  <reference>
    <citation>Ringhoffer M, Wiesneth M, Harsdorf S, Schlenk RF, Schmitt A, Reinhardt PP, Moessner M, Grimminger W, Mertens T, Reske SN, Dohner H, Bunjes D. CD34 cell selection of peripheral blood progenitor cells using the CliniMACS device for allogeneic transplantation: clinical results in 102 patients. Br J Haematol. 2004 Aug;126(4):527-35. doi: 10.1111/j.1365-2141.2004.05062.x.</citation>
    <PMID>15287946</PMID>
  </reference>
  <reference>
    <citation>Kao GS, Kim HT, Daley H, Ritz J, Burger SR, Kelley L, Vierra-Green C, Flesch S, Spellman S, Miller J, Confer D. Validation of short-term handling and storage conditions for marrow and peripheral blood stem cell products. Transfusion. 2011 Jan;51(1):137-47. doi: 10.1111/j.1537-2995.2010.02758.x.</citation>
    <PMID>20609197</PMID>
  </reference>
  <reference>
    <citation>Antonenas V, Garvin F, Webb M, Sartor M, Bradstock KF, Gottlieb D. Fresh PBSC harvests, but not BM, show temperature-related loss of CD34 viability during storage and transport. Cytotherapy. 2006;8(2):158-65. doi: 10.1080/14653240600620994.</citation>
    <PMID>16698689</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>February 28, 2022</last_update_submitted>
  <last_update_submitted_qc>February 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Edmund Waller</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>chronic myeloid leukemia</keyword>
  <keyword>myelodysplastic syndrome</keyword>
  <keyword>acute myeloid leukemia</keyword>
  <keyword>CD34+ cell mobilization therapy</keyword>
  <keyword>graft versus host disease</keyword>
  <keyword>allogeneic hematopoietic stem cell</keyword>
  <keyword>G-CSF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</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/NCT02258490
org study id: IRB00051037
secondary id: EPIC-HPC001
nct id: NCT02258490
lead sponsor: 
Allogeneic hematopoietic stem cell transplantation (HSCT) is an established form of treatment
      for hematological abnormalities. Poor graft function, occurs when there poor donor
      engraftment. A second infusion of unselected donor hematopoietic stem cells (HSC) can result
      in improvement, but can potentially increase the incidence of graft versus host disease.
      Cluster of differentiation 34+ (CD34+) selected stem cells depleted of T-cells is an
      attractive alternative for treatment of poor graft function as it may be associated with less
      Graft versus Host Disease (GVHD) and enhanced count recovery. The investigators are using the
      Miltenyi CliniMACS device and CD34 cell selection reagents for the preparation of allogeneic
      hematopoietic progenitor cell (HPC) transplants for patients who have had prior stem cell
      transplants and require a stem cell "boost" from the original donor.
This is a single-arm, open label, single institution, compassionate study which will enroll
      patients who are marginally engrafted and transfusion and/or growth factors dependent after
      allogeneic hematopoietic stem cell transplant (HSCT) regardless of the underlying disease for
      which the transplant was performed. Study subjects will receive a "booster" infusion of CD34+
      cell selected and T-cell depleted G-CSF mobilized apheresis product from the original stem
      cell donor in order to improve engraftment. The "booster" infusion will be administered
      without prior conditioning.
intervention type: Biological
intervention name: G-CSF mobilized CD34+ selected cells for transplantation
description: After screening and enrollment, donor will receive mobilization therapy with G-CSF (10 ug/Kg S/C daily x5-6 days) using standard National Marrow Donor Program guidelines. CD34+ cell selection will be performed according to procedures given in CliniMACS Operating Manual and institutional Standard Operating Procedures. If storage after CD34+ selection is necessary, product will be kept in a monitored refrigerator. During storage, leukocyte concentration should not exceed 2 x 108 cells/ml using platelet poor plasma to adjust cell concentration. If donor's plasma is not available, CliniMACS buffer will be used. Cell processing will be performed by personnel trained by Miltenyi on CliniMACS system prior to initiation of clinical product selection. After tests are performed and product passes release criteria, patient will receive final product. No conditioning regimen will be administered prior to cell infusion.
criteria: 
gender: All
minimum age: 17 Years
maximum age: 75 Years
last name: Edmund Waller, MD, PhD
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
citation: Davies SM, Weisdorf DJ, Haake RJ, Kersey JH, McGlave PB, Ramsay NK, Blazar BR. Second infusion of bone marrow for treatment of graft failure after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1994 Jul;14(1):73-7.
PMID: 7951123
citation: Elmaagacli AH, Peceny R, Steckel N, Trenschel R, Ottinger H, Grosse-Wilde H, Schaefer UW, Beelen DW. Outcome of transplantation of highly purified peripheral blood CD34+ cells with T-cell add-back compared with unmanipulated bone marrow or peripheral blood stem cells from HLA-identical sibling donors in patients with first chronic phase chronic myeloid leukemia. Blood. 2003 Jan 15;101(2):446-53. doi: 10.1182/blood-2002-05-1615. Epub 2002 Sep 12.
PMID: 12393406
citation: Lang P, Handgretinger R, Niethammer D, Schlegel PG, Schumm M, Greil J, Bader P, Engel C, Scheel-Walter H, Eyrich M, Klingebiel T. Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood. 2003 Feb 15;101(4):1630-6. doi: 10.1182/blood-2002-04-1203. Epub 2002 Oct 10.
PMID: 12393439
citation: Urbano-Ispizua A, Brunet S, Solano C, Moraleda JM, Rovira M, Zuazu J, de La Rubia J, Bargay J, Caballero D, Diez-Martin JL, Ojeda E, Perez de Oteiza JP, Ferra C, Espigado I, Alegre A, de La Serna J, Torres P, Riu C, Odriozola J, Rozman C, Sierra J, Garcia-Conde J, Montserrat E; Spanish Group of Allo-PBT. Allogeneic transplantation of CD34+-selected cells from peripheral blood in patients with myeloid malignancies in early phase: a case control comparison with unmodified peripheral blood transplantation. Bone Marrow Transplant. 2001 Aug;28(4):349-54. doi: 10.1038/sj.bmt.1703154.
PMID: 11571506
citation: Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, Bregante S, Lamparelli T, Tedone E, Oneto R, Frassoni F, Van Lint MT, Pogliani E, Bacigalupo A. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. 2006 Jul;91(7):935-40.
PMID: 16818281
citation: Tabilio A, Falzetti F, Zei T, De Ioanni M, Bonifacio E, Battelli F, Iacucci Ostini R, Ballanti S, Cimminiello M, Capponi M, Silvani C, Minelli O, Fettucciari K, Marconi P, Rosati E, Santucci A, Di Ianni M, Aversa F, Martelli MF. Graft engineering for allogeneic haploidentical stem cell transplantation. Blood Cells Mol Dis. 2004 Nov-Dec;33(3):274-80. doi: 10.1016/j.bcmd.2004.08.016.
PMID: 15528144
citation: Markiewicz M, Holowiecki J, Wojnar J, Krawczyk-Kulis M, Jagoda K, Giebel S, Kruzel T. Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients. Transplant Proc. 2004 Dec;36(10):3194-9. doi: 10.1016/j.transproceed.2004.09.052.
PMID: 15686727
citation: Oyekunle A, Koehl U, Schieder H, Ayuk F, Renges H, Fehse N, Zabelina T, Fehse B, Klingebiel T, Sputtek A, Zander A, Kroger N. CD34(+)-selected stem cell boost for delayed or insufficient engraftment after allogeneic stem cell transplantation. Cytotherapy. 2006;8(4):375-80. doi: 10.1080/14653240600735784.
PMID: 16923613
citation: Ringhoffer M, Wiesneth M, Harsdorf S, Schlenk RF, Schmitt A, Reinhardt PP, Moessner M, Grimminger W, Mertens T, Reske SN, Dohner H, Bunjes D. CD34 cell selection of peripheral blood progenitor cells using the CliniMACS device for allogeneic transplantation: clinical results in 102 patients. Br J Haematol. 2004 Aug;126(4):527-35. doi: 10.1111/j.1365-2141.2004.05062.x.
PMID: 15287946
citation: Kao GS, Kim HT, Daley H, Ritz J, Burger SR, Kelley L, Vierra-Green C, Flesch S, Spellman S, Miller J, Confer D. Validation of short-term handling and storage conditions for marrow and peripheral blood stem cell products. Transfusion. 2011 Jan;51(1):137-47. doi: 10.1111/j.1537-2995.2010.02758.x.
PMID: 20609197
citation: Antonenas V, Garvin F, Webb M, Sartor M, Bradstock KF, Gottlieb D. Fresh PBSC harvests, but not BM, show temperature-related loss of CD34 viability during storage and transport. Cytotherapy. 2006;8(2):158-65. doi: 10.1080/14653240600620994.
PMID: 16698689
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Edmund Waller
investigator title: Principal Investigator
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Myelodysplastic Syndromes