<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/NCT02231853</url>
  </required_header>
  <id_info>
    <org_study_id>140182</org_study_id>
    <secondary_id>14-H-0182</secondary_id>
    <nct_id>NCT02231853</nct_id>
  </id_info>
  <brief_title>Phase I/II Trial of Early Infusion of Rapidly-generated Multivirus Specific T Cells (MVST) to Prevent Post Transplant Viral Infections</brief_title>
  <official_title>Phase I/II Trial of Early Infusion of Rapidly-generated Multivirus Specific T Cells (MVST) to Prevent Post Transplant Viral Infections</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Allogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life&#xD;
      threatening viral reactivation. Conventional antiviral therapy is suboptimal for&#xD;
      cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK&#xD;
      virus (BKV). An alternative approach to prevent viral reactivation is to infuse&#xD;
      virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such&#xD;
      multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to&#xD;
      prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi&#xD;
      virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral&#xD;
      antigens and expanded in vitro before infusion into the transplant recipient. Viral&#xD;
      reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation&#xD;
      is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate&#xD;
      post-SCT period has not been previously studied. This protocol will be the first of a planned&#xD;
      series of cellular therapies to be layered on our existing T lymphocyte depleted transplant&#xD;
      platform protocol 13-H-0144.&#xD;
&#xD;
      The aim of this study is to determine the safety and efficacy of very early infusion of MVST&#xD;
      directed against the four most common viruses causing complications after T-depleted SCT.&#xD;
      GMP-grade allogeneic MVST from the stem cell donor will be generated using monocyte-derived&#xD;
      donor dendritic cells (DCs) pulsed with overlapping peptide libraries of immunodominant&#xD;
      antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 10-14&#xD;
      days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem&#xD;
      cell mobilization will be used to generate the MVST cells. MVST passing release criteria will&#xD;
      be cryopreserved ready for infusion post SCT.&#xD;
&#xD;
      Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVST&#xD;
      within 30 days (target day +14, range 0-30 days) post SCT. Phase I safety monitoring will&#xD;
      continue for 6 weeks. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by&#xD;
      serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent&#xD;
      herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding&#xD;
      threshold for treatment, or those with clinically overt viral disease will receive&#xD;
      conventional antiviral treatment. Patients developing acute GVHD will receive standard&#xD;
      treatment with systemic steroids. These patients are eligible for reinfusion of MVST when&#xD;
      steroids are tapered.&#xD;
&#xD;
      The clinical trial is designed as a single institution, open label, non-randomized Phase I/II&#xD;
      trial of MVST in transplant recipients, designed as 3-cohort dose escalation Phase I followed&#xD;
      by a 20 subject extension Phase II at the maximum tolerated dose of cells. Safety will be&#xD;
      monitored continuously for a period of 6 weeks post T cell transfer. The primary safety&#xD;
      endpoint will be the occurrence of dose limiting toxicity, defined as the occurrence of Grade&#xD;
      IV GVHD or any other SAE that is deemed to be at least probably or definitely related to the&#xD;
      investigational product. The primary efficacy endpoint for the phase II will be the&#xD;
      proportion of CMV reactivation requiring treatment at day 100 post transplant. Secondary&#xD;
      endpoints are technical feasibility of MSVT manufacture, patterns of virus reactivation by&#xD;
      PCR, and clinical disease from EBV, Ad, BK, day 100 non-relapse mortality.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Allogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life&#xD;
      threatening viral reactivation. Conventional antiviral therapy is suboptimal for&#xD;
      cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK&#xD;
      virus (BKV). An alternative approach to prevent viral reactivation is to infuse&#xD;
      virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such&#xD;
      multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to&#xD;
      prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi&#xD;
      virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral&#xD;
      antigens and expanded in vitro before infusion into the transplant recipient. Viral&#xD;
      reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation&#xD;
      is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate&#xD;
      post-SCT period has not been previously studied. This protocol will be the first of a planned&#xD;
      series of cellular therapies to be layered on our existing T lymphocyte depleted transplant&#xD;
      platform protocol 13-H-0144.&#xD;
&#xD;
      The aim of this study is to determine the safety and efficacy of very early infusion of MVSTr&#xD;
      cells directed against the four most common viruses causing complications after T-depleted&#xD;
      SCT. GMP-grade allogeneic MVSTr from the stem cell donor will be generated using or&#xD;
      peripheral blood mononuclear cells (PBMCs) pulsed with overlapping peptide libraries of&#xD;
      immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by&#xD;
      IL-2 for 14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained&#xD;
      prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release&#xD;
      criteria will be cryopreserved ready for infusion post SCT.&#xD;
&#xD;
      Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVSTr&#xD;
      on day +7 post transplant range 0-14 days) post SCT. Phase I safety monitoring will continue&#xD;
      for 6 weeks after infusion. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by&#xD;
      serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent&#xD;
      herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding&#xD;
      threshold for treatment, or those with clinically overt viral disease will receive&#xD;
      conventional antiviral treatment. Patients developing acute GVHD will receive standard&#xD;
      treatment with systemic steroids. These patients are eligible for reinfusion of MVST when&#xD;
      steroids are tapered.&#xD;
&#xD;
      The clinical trial is designed as a single institution, open label, non-randomized Phase I&#xD;
      trial of MVSTr in transplant recipients, designed as a single cohort Phase I study. Safety&#xD;
      will be monitored continuously for a period of 6 weeks post MVSTr transfer. The primary&#xD;
      safety endpoint will be the occurrence of dose limiting toxicity (DLT), defined as the&#xD;
      occurrence of Grade IV GVHD, Grade III cytokine release syndrome (CRS), Grade III&#xD;
      autoimmunity or any other SAE that is deemed to be at least probably or definitely related to&#xD;
      the investigational product.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>September 3, 2014</start_date>
  <completion_date type="Actual">December 29, 2017</completion_date>
  <primary_completion_date type="Actual">November 17, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of dose limiting toxicity</measure>
    <time_frame>6 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>EBV, Ad, BK, day 100 non-relapse mort.</measure>
    <time_frame>100 days</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>CML (Chronic Myelogenous Leukemia)</condition>
  <condition>MDS (Myelodysplastic Syndrome)</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>AML (Acute Myelogenous Leukemia)</condition>
  <arm_group>
    <arm_group_label>-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1x10e4 MVST/kg infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1x10e5 MVST/kg infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5x10e5 MVST/kg infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1x10e6 MVST/kg infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1x10e6 MVSTr/kg infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5x10e6 MVSTr/kg infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MVST</intervention_name>
    <description>MVST Infusion</description>
    <arm_group_label>-1</arm_group_label>
    <arm_group_label>1</arm_group_label>
    <arm_group_label>2</arm_group_label>
    <arm_group_label>3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MVSTr</intervention_name>
    <description>PBMCs will be collected by apheresis prior to mobilization for Hematopoietic stem cells collection, donor apheresis will be used partially to prepare DLIs per PI specification and remaining will be further processed by elutriation.&#xD;
Monocytes and Lymphocytes are cryopreserved for further manufacture of MVSTr.</description>
    <arm_group_label>3B</arm_group_label>
    <arm_group_label>4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA: Recipient&#xD;
&#xD;
          -  Ages 18-75 years inclusive&#xD;
&#xD;
          -  Patients with hematologic malignancies who have signed consent for NHLBI transplant&#xD;
             protocol 13-H-0144.&#xD;
&#xD;
          -  Susceptible to CMV reactivation post transplant (either donor or recipient need to be&#xD;
             seropositive for CMV at any time prior to transplant).&#xD;
&#xD;
          -  Ability to comprehend the investigational nature of the study and provide informed&#xD;
             consent.&#xD;
&#xD;
        EXCLUSION CRITERIA: Recipient&#xD;
&#xD;
          -  Positive pregnancy test for women of childbearing age.&#xD;
&#xD;
          -  DLCO adjusted for Hb and ventilation &lt; 50% predicted prior to SCT&#xD;
&#xD;
          -  Left ventricular ejection fraction &lt; 40% (evaluated by ECHO) or &lt; 30% (evaluated by&#xD;
             MUGA) prior to SCT&#xD;
&#xD;
          -  AST/SGOT &gt; 10 times ULN (&gt;grade 3, CTCAE)&#xD;
&#xD;
          -  Bilirubin &gt; 5 times ULN (&gt;grade 3, CTCAE)&#xD;
&#xD;
          -  Estimated GFR &lt; 15 mL/min&#xD;
&#xD;
          -  Receiving Ganciclovir, Foscarnet or Cidofovir&#xD;
&#xD;
          -  Receiving corticosteroids at the dose equivalent to 0.5 mg/kg/day of&#xD;
             methylprednisolone&#xD;
&#xD;
          -  Evidence of active autoimmune process&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Minocher M Battiwalla, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Heart, Lung, and Blood Institute (NHLBI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center, 9000 Rockville Pike</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Gerdemann U, Keirnan JM, Katari UL, Yanagisawa R, Christin AS, Huye LE, Perna SK, Ennamuri S, Gottschalk S, Brenner MK, Heslop HE, Rooney CM, Leen AM. Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Mol Ther. 2012 Aug;20(8):1622-32. doi: 10.1038/mt.2012.130. Epub 2012 Jul 17.</citation>
    <PMID>22801446</PMID>
  </reference>
  <reference>
    <citation>Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995 Oct 19;333(16):1038-44. doi: 10.1056/NEJM199510193331603.</citation>
    <PMID>7675046</PMID>
  </reference>
  <reference>
    <citation>Blyth E, Clancy L, Simms R, Ma CK, Burgess J, Deo S, Byth K, Dubosq MC, Shaw PJ, Micklethwaite KP, Gottlieb DJ. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood. 2013 May 2;121(18):3745-58. doi: 10.1182/blood-2012-08-448977. Epub 2013 Feb 22.</citation>
    <PMID>23435462</PMID>
  </reference>
  <verification_date>December 29, 2017</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>December 14, 2019</last_update_submitted>
  <last_update_submitted_qc>December 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BK Virus</keyword>
  <keyword>Cytotoxic T Cells</keyword>
  <keyword>EBV</keyword>
  <keyword>Adenovirus</keyword>
  <keyword>CMV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</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/NCT02231853
org study id: 140182
secondary id: 14-H-0182
nct id: NCT02231853
lead sponsor: 
Allogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life
      threatening viral reactivation. Conventional antiviral therapy is suboptimal for
      cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK
      virus (BKV). An alternative approach to prevent viral reactivation is to infuse
      virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such
      multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to
      prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi
      virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral
      antigens and expanded in vitro before infusion into the transplant recipient. Viral
      reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation
      is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate
      post-SCT period has not been previously studied. This protocol will be the first of a planned
      series of cellular therapies to be layered on our existing T lymphocyte depleted transplant
      platform protocol 13-H-0144.

      The aim of this study is to determine the safety and efficacy of very early infusion of MVST
      directed against the four most common viruses causing complications after T-depleted SCT.
      GMP-grade allogeneic MVST from the stem cell donor will be generated using monocyte-derived
      donor dendritic cells (DCs) pulsed with overlapping peptide libraries of immunodominant
      antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 10-14
      days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem
      cell mobilization will be used to generate the MVST cells. MVST passing release criteria will
      be cryopreserved ready for infusion post SCT.

      Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVST
      within 30 days (target day +14, range 0-30 days) post SCT. Phase I safety monitoring will
      continue for 6 weeks. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by
      serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent
      herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding
      threshold for treatment, or those with clinically overt viral disease will receive
      conventional antiviral treatment. Patients developing acute GVHD will receive standard
      treatment with systemic steroids. These patients are eligible for reinfusion of MVST when
      steroids are tapered.

      The clinical trial is designed as a single institution, open label, non-randomized Phase I/II
      trial of MVST in transplant recipients, designed as 3-cohort dose escalation Phase I followed
      by a 20 subject extension Phase II at the maximum tolerated dose of cells. Safety will be
      monitored continuously for a period of 6 weeks post T cell transfer. The primary safety
      endpoint will be the occurrence of dose limiting toxicity, defined as the occurrence of Grade
      IV GVHD or any other SAE that is deemed to be at least probably or definitely related to the
      investigational product. The primary efficacy endpoint for the phase II will be the
      proportion of CMV reactivation requiring treatment at day 100 post transplant. Secondary
      endpoints are technical feasibility of MSVT manufacture, patterns of virus reactivation by
      PCR, and clinical disease from EBV, Ad, BK, day 100 non-relapse mortality.
Allogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life
      threatening viral reactivation. Conventional antiviral therapy is suboptimal for
      cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK
      virus (BKV). An alternative approach to prevent viral reactivation is to infuse
      virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such
      multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to
      prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi
      virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral
      antigens and expanded in vitro before infusion into the transplant recipient. Viral
      reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation
      is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate
      post-SCT period has not been previously studied. This protocol will be the first of a planned
      series of cellular therapies to be layered on our existing T lymphocyte depleted transplant
      platform protocol 13-H-0144.

      The aim of this study is to determine the safety and efficacy of very early infusion of MVSTr
      cells directed against the four most common viruses causing complications after T-depleted
      SCT. GMP-grade allogeneic MVSTr from the stem cell donor will be generated using or
      peripheral blood mononuclear cells (PBMCs) pulsed with overlapping peptide libraries of
      immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by
      IL-2 for 14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained
      prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release
      criteria will be cryopreserved ready for infusion post SCT.

      Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVSTr
      on day +7 post transplant range 0-14 days) post SCT. Phase I safety monitoring will continue
      for 6 weeks after infusion. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by
      serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent
      herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding
      threshold for treatment, or those with clinically overt viral disease will receive
      conventional antiviral treatment. Patients developing acute GVHD will receive standard
      treatment with systemic steroids. These patients are eligible for reinfusion of MVST when
      steroids are tapered.

      The clinical trial is designed as a single institution, open label, non-randomized Phase I
      trial of MVSTr in transplant recipients, designed as a single cohort Phase I study. Safety
      will be monitored continuously for a period of 6 weeks post MVSTr transfer. The primary
      safety endpoint will be the occurrence of dose limiting toxicity (DLT), defined as the
      occurrence of Grade IV GVHD, Grade III cytokine release syndrome (CRS), Grade III
      autoimmunity or any other SAE that is deemed to be at least probably or definitely related to
      the investigational product.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Occurrence of dose limiting toxicity
time frame: 6 weeks
measure: EBV, Ad, BK, day 100 non-relapse mort.
time frame: 100 days
arm group label: -1
arm group type: Experimental
description: 1x10e4 MVST/kg infusion
arm group label: 1
arm group type: Experimental
description: 1x10e5 MVST/kg infusion
arm group label: 2
arm group type: Experimental
description: 5x10e5 MVST/kg infusion
arm group label: 3
arm group type: Experimental
description: 1x10e6 MVST/kg infusion
arm group label: 3B
arm group type: Experimental
description: 1x10e6 MVSTr/kg infusion
arm group label: 4
arm group type: Experimental
description: 5x10e6 MVSTr/kg infusion
intervention type: Biological
intervention name: MVST
description: MVST Infusion
arm group label: -1
arm group label: 1
arm group label: 2
arm group label: 3
intervention type: Biological
intervention name: MVSTr
description: PBMCs will be collected by apheresis prior to mobilization for Hematopoietic stem cells collection, donor apheresis will be used partially to prepare DLIs per PI specification and remaining will be further processed by elutriation.
Monocytes and Lymphocytes are cryopreserved for further manufacture of MVSTr.
arm group label: 3B
arm group label: 4
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Minocher M Battiwalla, M.D.
role: Principal Investigator
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
facility: 
country: United States
citation: Gerdemann U, Keirnan JM, Katari UL, Yanagisawa R, Christin AS, Huye LE, Perna SK, Ennamuri S, Gottschalk S, Brenner MK, Heslop HE, Rooney CM, Leen AM. Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Mol Ther. 2012 Aug;20(8):1622-32. doi: 10.1038/mt.2012.130. Epub 2012 Jul 17.
PMID: 22801446
citation: Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995 Oct 19;333(16):1038-44. doi: 10.1056/NEJM199510193331603.
PMID: 7675046
citation: Blyth E, Clancy L, Simms R, Ma CK, Burgess J, Deo S, Byth K, Dubosq MC, Shaw PJ, Micklethwaite KP, Gottlieb DJ. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood. 2013 May 2;121(18):3745-58. doi: 10.1182/blood-2012-08-448977. Epub 2013 Feb 22.
PMID: 23435462
responsible party type: Sponsor
mesh term: Virus Diseases
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Leukemia, Myeloid, Acute
mesh term: Myelodysplastic Syndromes