xml: <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/NCT06011486</url>
    </required_header>
    <id_info>
      <org_study_id>U1111-1226-7367</org_study_id>
      <nct_id>NCT06011486</nct_id>
    </id_info>
    <brief_title>Expansion of Virus-Specific Lymphocytes for Cell Therapy</brief_title>
    <official_title>Expansion of Virus-Specific Lymphocytes for Cell Therapy in Immunosuppressed Patients Who Underwent Bone Marrow Transplantation.</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>
        Infections and reactivation of human cytomegalovirus (CMV), adenovirus, Epstein-barr and&#xD;
        polyoma virus infections are frequent causes of morbidity and mortality and are a source of&#xD;
        serious complications in patients undergoing allogeneic bone marrow transplantation.&#xD;
  &#xD;
        In this project we will prepare specific T lymphocytes from blood donor, select cells&#xD;
        CMV-specific by interferon gamma capture and treat patients with CMV viral infections. These&#xD;
        cells will be used as antiviral therapy in transplanted patients whom do not respond to&#xD;
        conventional therapies or in patients whose conventional therapy may be toxic in the context&#xD;
        of transplantation. In this context, CMV reactivation can lead to serious complications in&#xD;
        patients, such as irreversible neurological changes, pulmonary, gastrointestinal and&#xD;
        ophthalmologic complications, among others, in addition to prolonged hospitalizations,&#xD;
        leading to significant morbidity and mortality , both in the health sector public as private.&#xD;
  &#xD;
        This project may represent an important therapeutic modality using cell of the shelf as a&#xD;
        source of therapy for different patients and contributing to reduced morbidity / mortality&#xD;
        after transplantation, as well as a reduction in the hospitalization period.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The proposed clinical trial is a phase I single-arm infusion study of cytomegalovirus&#xD;
        (CMV)-specific lymphocytes derived from buffy-coat derivatives of platelet donors&#xD;
        (ImmuneCellVir-I). T lymphocytes are expanded, stimulated with peptide (pp65) from the viral&#xD;
        capsid and selected according to interferon-γ (INF-γ) production in response to the stimulus.&#xD;
        After selection, the lymphocytes will be frozen and released for infusion into recipients&#xD;
        according to HLA compatibility, result of aerobic/anaerobic cultures and special&#xD;
        microorganisms/fungi, endotoxin, donor serological assays, PCR for CMV, EBV and B19 of the&#xD;
        product, NAT HCV, HIV, HBS and HTLV-1/2 of the product, and results of impurity and potency&#xD;
        tests of the product.&#xD;
  &#xD;
        The main objective of the study is to evaluate the safety and tolerability of Cytomegalovirus&#xD;
        (CMV)-specific Lymphocyte infusion in patients with CMV infection who do not respond to&#xD;
        conventional therapies or whose pharmacological therapy may be toxic in the post-transplant&#xD;
        context. As secondary outcome to determine the effectiveness of the infusion of CMV-specific&#xD;
        lymphocytes The main benefit to potential participants is the treatment of cytomegalovirus&#xD;
        infection for patients who are refractory or intolerant to the established drug treatment.&#xD;
        Furthermore, the infusion of CMV-specific lymphocytes could potentially help in the immune&#xD;
        reconstitution of patients. The expectation is that, with this therapeutic modality, it will&#xD;
        be possible to treat patients who have no other treatment alternative. While, the known&#xD;
        possible risks are related to cryopreserved allogeneic product infusion reactions and&#xD;
        potential risk of graft versus host disease.&#xD;
  &#xD;
        The possible mechanism of action of this therapy would be through the infused CMV-specific&#xD;
        donor cells that would recognize the CMV-infected cells in the patient. CD4 T lymphocytes&#xD;
        amplify the immune response by secreting cytokines, CD8 T lymphocytes attack CMV-infected&#xD;
        cells, releasing perforins and granzymes.&#xD;
  &#xD;
        Cytomegalovirus (CMV)-specific lymphocytes will be administered intravenously. Patients will&#xD;
        receive therapy containing a total amount of 1x106 CMV-specific T lymphocytes, equivalent to&#xD;
        a 1-2x104 dose/kg of recipient weight, which can be repeated on up to 2 occasions with a&#xD;
        minimum interval of 2 weeks between infusions, if the patient persists with the presence of&#xD;
        inclusion criteria in the study. The trial will be performed in accordance with protocol,&#xD;
        good clinical practice and regulatory requirements.&#xD;
  &#xD;
        At this time, it is not possible to state that all research participants will benefit&#xD;
        directly from this study. However, its development will allow a better knowledge of this&#xD;
        cellular therapy, allowing an improvement of the protocol and greater efficiency in future&#xD;
        protocols to be carried out. It is expected that the proposed treatment generates at least a&#xD;
        better quality of life for research participants, with a decrease in complications resulting&#xD;
        from the disease.&#xD;
  &#xD;
        Infusion reactions, development of graft versus host disease (GvHD) and Immunogenicity The&#xD;
        primary outcomes of safety of ImmuneCellvir -I will be verified in the patients that will be&#xD;
        followed during infusion and 7 consecutive weeks after infusion, and also 100, 180 and 365&#xD;
        days. After cell infusion, patients will be monitored for vital signs (mmHg), pulse rate and&#xD;
        blood oxygen level every 15 minutes and must be instructed to contact the study team for any&#xD;
        unusual symptoms. After infusion, will be 6 visits (1/week) and 100 days, 6 months and 1&#xD;
        year, after infusion. Patients will be followed for clinical signs and symptoms of acute and&#xD;
        chronic GvHD , as gastrointestinal tract alterations, skin, eye, liver, musculoskeletal and&#xD;
        lung changes. Patient will be tested for 7 weeks for Bilirubin (μmol/L), Alkaline phosphatase&#xD;
        (U/L), Gamma-glutamyl Transferase (U/L) , glutamic-oxaloacetic transaminase/ glutamic pyruvic&#xD;
        transaminase (U/L), blood cells count (cells/mm3), creatinine (mg/dL), urea(mg/dL), Serum&#xD;
        level of tacrolimus/cyclosporine (mg/dL). For Immunogenicity will be measured the development&#xD;
        of anti Human Leukocyte Antigen antibodies in the patient.&#xD;
  &#xD;
        The secondary outcome will be measured by the evaluation of clinical symptoms score, level of&#xD;
        CMV copies and anti-CMV response. The secondary or exploratory outcome will be performed for&#xD;
        as indicative of efficacy. This outcome will be reported as a score of clinical symptoms,&#xD;
        comparing the symptoms before and after the infusion. Laboratorial tests will be performed&#xD;
        for 7 consecutive weeks after the infusion to demonstrated the patient clinical improvement&#xD;
        as the rate of CMV viral load (copies/mL), rate of anti-CMV response in the peripheral blood&#xD;
        of patients by ELISpot (IFN-y spots/10x6cells). The patients can be also evaluated for&#xD;
        specific exams (if required) depend on the site of infection as computed tomography,&#xD;
        colonoscopy, eye fundus examination and biopsy. In addition, assays to determine cell&#xD;
        biodistribution as chimerism (%) after infusion will be performed.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 10, 2023</start_date>
    <completion_date type="Anticipated">June 10, 2026</completion_date>
    <primary_completion_date type="Anticipated">June 10, 2024</primary_completion_date>
    <phase>Phase 1</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>Number of patients with immediate infusion reactions</measure>
      <time_frame>3 hours</time_frame>
      <description>Safety of cytotoxic T cell (CTL) based on patients with grade 3 immediate adverse events that are at least possibly related to the CTL infusion within 3 hours of the CTL infusion, using the grade as follows: Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe with Life-threatening consequences.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Development of Acute graft versus host disease (GvHD)</measure>
      <time_frame>6 weeks</time_frame>
      <description>Number of Patients that present Acute GvHD Grades III-IV [ Time Frame: 6 weeks] Safety of cytotoxic T Cell (CTL) will be based on patients with acute GvHD grades III-IV within 6 weeks after the last dose of CTL. Acute GVHD grading will be performed according to NIH criteria (1). Grade 0 represents no acute GvHD. Grade 4 represents the most severe acute GvHD.&#xD;
  1-Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, et al. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Development of Non-Hematological Adverse events</measure>
      <time_frame>6 weeks</time_frame>
      <description>Number of Patients With Grades 3 Non-hematologic Adverse Events Related to the T Cell Product [ Time Frame: 6 weeks ] Safety of VSTs based on patients with grade 3 non-hematologic adverse events that are at least possibly related to the CTL infusion within 6 weeks of the last CTL dose, using the grade as follows: Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe with Life-threatening consequences.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Risk for chronic GVHD [ Time Frame: At 6 and12 months post CTL infusion ]</measure>
      <time_frame>6 to 12 montas</time_frame>
      <description>Survival analysis method will be applied. Time to chronic GVHD will be defined from time of the last CTL infusion to the onset of chronic GVHD, or the last clinical assessment date if no chronic GVHD. Cumulative incidence of chronic GVHD at 6 and 12 months will be estimated.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Antiviral activity defined as response to viral load [ Time Frame: 6 weeks ]</measure>
      <time_frame>6 weeks</time_frame>
      <description>Complete response, partial , or no response will be defined and proportion of each outcome will be calculated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of anti-CMV response improvement in the peripheral blood of participants [ Time Frame: 6 weeks ]</measure>
      <time_frame>6 weeks</time_frame>
      <description>Anti-CMV response will be measured by ELISpot (IFN-y spots/10e6 cells)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical response to CTL infusions [ Time Frame: At 6 weeks and 3 months ]</measure>
      <time_frame>6 weeks and 3 month</time_frame>
      <description>In cases with CMV disease, clinical response can be evaluated with evaluation of the involved organ with specific exams (if required) as computed tomography, colonoscopy, eye fundus examination and biopsy .</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">10</enrollment>
    <condition>CMV Viremia</condition>
    <condition>CMV</condition>
    <arm_group>
      <arm_group_label>Lymphocyte infusion</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with CMV disease or reactivation will be included for receiving donor-CMV-specific cells</description>
    </arm_group>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>Lymphocyte infusion (ImmuneCellVir-I)</intervention_name>
      <description>Infusion of donor CMV specific cells into patients eligible to the trial</description>
      <arm_group_label>Lymphocyte infusion</arm_group_label>
      <other_name>CMV-specific cells infusion</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Be able to provide signed informed consent.&#xD;
  &#xD;
            -  Must be between 18 and 75 years old at the time of signing the consent form&#xD;
  &#xD;
            -  Having undergone allogeneic hematopoietic stem cell transplantation (related,&#xD;
               unrelated, haploidentical or cord blood transplant)&#xD;
  &#xD;
            -  Negative pregnancy test for women of childbearing age (non-fertile age defined as&#xD;
               post-menopausal over one year, or surgically sterilized); Acceptance of the use of&#xD;
               contraceptive methods by sexually active men and women of childbearing age;&#xD;
  &#xD;
            -  Present with clinically significant CMV infection and one of the following conditions:&#xD;
  &#xD;
            -  Refractory CMV infection, defined as over a 1log increase in blood or plasma CMV&#xD;
               copies number after 2 weeks of treatment with appropriate anti-CMV medication&#xD;
               (treatment with ganciclovir, valganciclovir, or foscarnet)&#xD;
  &#xD;
            -  Probable refractory CMV infection, defined as persistence of CMV DNA in blood or&#xD;
               plasma at the same level or under 1 log increase after 2 weeks of treatment with&#xD;
               appropriate anti-CMV medication (treatment with ganciclovir, valganciclovir, or&#xD;
               foscarnet)&#xD;
  &#xD;
            -  Presence of resistant CMV, defined by the presence of a known genetic mutation that&#xD;
               reduces susceptibility to one or more antiviral medications&#xD;
  &#xD;
            -  Refractory CMV disease, defined as worsening of signs and symptoms and/or progression&#xD;
               to CMV disease after 2 weeks of appropriate antiviral therapy&#xD;
  &#xD;
            -  Restrictions or complications related to conventional therapy, which make it&#xD;
               impossible to carry out conventional drug treatment defined as cytopenias with&#xD;
               neutrophils under 1000 per microliter, platelets under 100,000 per microliter related&#xD;
               to the use of ganciclovir or valganciclovir and nephrotoxicity with an increase of 1.5&#xD;
               times in the baseline creatinine with the use of foscavir.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients who do not meet the inclusion criteria&#xD;
  &#xD;
            -  Patients who do not agree to participate in the study or sign the consent form&#xD;
  &#xD;
            -  Patients reporting allergy to murine antibodies or iron-dextran&#xD;
  &#xD;
            -  Patients with grade 3 or 4 graft versus host disease/graft versus host disease in&#xD;
               activity/treatment&#xD;
  &#xD;
            -  Pregnant or lactating patients&#xD;
  &#xD;
            -  Patients with uncontrolled bacterial and/or fungal infections&#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>Nelson Hamerschlak, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Hospital Israelita Albert Einstein</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Nelson C Hamerschlak, MD, PhD</last_name>
      <phone>+5511999614340</phone>
      <email>hamer@einstein.br</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Luciana C Marti, PhD</last_name>
      <phone>+5511983716733</phone>
      <email>luciana.marti@einstein.br</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Hospital Israelita Albert Einstein</name>
        <address>
          <city>São Paulo</city>
          <state>SP</state>
          <zip>05653000</zip>
          <country>Brazil</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Nelson Hamerschlak, MD, PhD</last_name>
        <phone>+5511999614340</phone>
        <email>hamer@einstein.br</email>
      </contact>
      <contact_backup>
        <last_name>Luciana C Marti, PhD</last_name>
        <phone>+5511983716733</phone>
        <email>luciana.marti@einstein.br</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Brazil</country>
    </location_countries>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>June 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Viremia</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06011486
  org study id: U1111-1226-7367
  nct id: NCT06011486
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Infections and reactivation of human cytomegalovirus (CMV), adenovirus, Epstein-barr and
        polyoma virus infections are frequent causes of morbidity and mortality and are a source of
        serious complications in patients undergoing allogeneic bone marrow transplantation.
  
        In this project we will prepare specific T lymphocytes from blood donor, select cells
        CMV-specific by interferon gamma capture and treat patients with CMV viral infections. These
        cells will be used as antiviral therapy in transplanted patients whom do not respond to
        conventional therapies or in patients whose conventional therapy may be toxic in the context
        of transplantation. In this context, CMV reactivation can lead to serious complications in
        patients, such as irreversible neurological changes, pulmonary, gastrointestinal and
        ophthalmologic complications, among others, in addition to prolonged hospitalizations,
        leading to significant morbidity and mortality , both in the health sector public as private.
  
        This project may represent an important therapeutic modality using cell of the shelf as a
        source of therapy for different patients and contributing to reduced morbidity / mortality
        after transplantation, as well as a reduction in the hospitalization period.
  The proposed clinical trial is a phase I single-arm infusion study of cytomegalovirus
        (CMV)-specific lymphocytes derived from buffy-coat derivatives of platelet donors
        (ImmuneCellVir-I). T lymphocytes are expanded, stimulated with peptide (pp65) from the viral
        capsid and selected according to interferon-γ (INF-γ) production in response to the stimulus.
        After selection, the lymphocytes will be frozen and released for infusion into recipients
        according to HLA compatibility, result of aerobic/anaerobic cultures and special
        microorganisms/fungi, endotoxin, donor serological assays, PCR for CMV, EBV and B19 of the
        product, NAT HCV, HIV, HBS and HTLV-1/2 of the product, and results of impurity and potency
        tests of the product.
  
        The main objective of the study is to evaluate the safety and tolerability of Cytomegalovirus
        (CMV)-specific Lymphocyte infusion in patients with CMV infection who do not respond to
        conventional therapies or whose pharmacological therapy may be toxic in the post-transplant
        context. As secondary outcome to determine the effectiveness of the infusion of CMV-specific
        lymphocytes The main benefit to potential participants is the treatment of cytomegalovirus
        infection for patients who are refractory or intolerant to the established drug treatment.
        Furthermore, the infusion of CMV-specific lymphocytes could potentially help in the immune
        reconstitution of patients. The expectation is that, with this therapeutic modality, it will
        be possible to treat patients who have no other treatment alternative. While, the known
        possible risks are related to cryopreserved allogeneic product infusion reactions and
        potential risk of graft versus host disease.
  
        The possible mechanism of action of this therapy would be through the infused CMV-specific
        donor cells that would recognize the CMV-infected cells in the patient. CD4 T lymphocytes
        amplify the immune response by secreting cytokines, CD8 T lymphocytes attack CMV-infected
        cells, releasing perforins and granzymes.
  
        Cytomegalovirus (CMV)-specific lymphocytes will be administered intravenously. Patients will
        receive therapy containing a total amount of 1x106 CMV-specific T lymphocytes, equivalent to
        a 1-2x104 dose/kg of recipient weight, which can be repeated on up to 2 occasions with a
        minimum interval of 2 weeks between infusions, if the patient persists with the presence of
        inclusion criteria in the study. The trial will be performed in accordance with protocol,
        good clinical practice and regulatory requirements.
  
        At this time, it is not possible to state that all research participants will benefit
        directly from this study. However, its development will allow a better knowledge of this
        cellular therapy, allowing an improvement of the protocol and greater efficiency in future
        protocols to be carried out. It is expected that the proposed treatment generates at least a
        better quality of life for research participants, with a decrease in complications resulting
        from the disease.
  
        Infusion reactions, development of graft versus host disease (GvHD) and Immunogenicity The
        primary outcomes of safety of ImmuneCellvir -I will be verified in the patients that will be
        followed during infusion and 7 consecutive weeks after infusion, and also 100, 180 and 365
        days. After cell infusion, patients will be monitored for vital signs (mmHg), pulse rate and
        blood oxygen level every 15 minutes and must be instructed to contact the study team for any
        unusual symptoms. After infusion, will be 6 visits (1/week) and 100 days, 6 months and 1
        year, after infusion. Patients will be followed for clinical signs and symptoms of acute and
        chronic GvHD , as gastrointestinal tract alterations, skin, eye, liver, musculoskeletal and
        lung changes. Patient will be tested for 7 weeks for Bilirubin (μmol/L), Alkaline phosphatase
        (U/L), Gamma-glutamyl Transferase (U/L) , glutamic-oxaloacetic transaminase/ glutamic pyruvic
        transaminase (U/L), blood cells count (cells/mm3), creatinine (mg/dL), urea(mg/dL), Serum
        level of tacrolimus/cyclosporine (mg/dL). For Immunogenicity will be measured the development
        of anti Human Leukocyte Antigen antibodies in the patient.
  
        The secondary outcome will be measured by the evaluation of clinical symptoms score, level of
        CMV copies and anti-CMV response. The secondary or exploratory outcome will be performed for
        as indicative of efficacy. This outcome will be reported as a score of clinical symptoms,
        comparing the symptoms before and after the infusion. Laboratorial tests will be performed
        for 7 consecutive weeks after the infusion to demonstrated the patient clinical improvement
        as the rate of CMV viral load (copies/mL), rate of anti-CMV response in the peripheral blood
        of patients by ELISpot (IFN-y spots/10x6cells). The patients can be also evaluated for
        specific exams (if required) depend on the site of infection as computed tomography,
        colonoscopy, eye fundus examination and biopsy. In addition, assays to determine cell
        biodistribution as chimerism (%) after infusion will be performed.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of patients with immediate infusion reactions
  time frame: 3 hours
  description: Safety of cytotoxic T cell (CTL) based on patients with grade 3 immediate adverse events that are at least possibly related to the CTL infusion within 3 hours of the CTL infusion, using the grade as follows: Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe with Life-threatening consequences.
  measure: Development of Acute graft versus host disease (GvHD)
  time frame: 6 weeks
  description: Number of Patients that present Acute GvHD Grades III-IV [ Time Frame: 6 weeks] Safety of cytotoxic T Cell (CTL) will be based on patients with acute GvHD grades III-IV within 6 weeks after the last dose of CTL. Acute GVHD grading will be performed according to NIH criteria (1). Grade 0 represents no acute GvHD. Grade 4 represents the most severe acute GvHD.
  1-Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, et al. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10.
  measure: Development of Non-Hematological Adverse events
  time frame: 6 weeks
  description: Number of Patients With Grades 3 Non-hematologic Adverse Events Related to the T Cell Product [ Time Frame: 6 weeks ] Safety of VSTs based on patients with grade 3 non-hematologic adverse events that are at least possibly related to the CTL infusion within 6 weeks of the last CTL dose, using the grade as follows: Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe with Life-threatening consequences.
  measure: Risk for chronic GVHD [ Time Frame: At 6 and12 months post CTL infusion ]
  time frame: 6 to 12 montas
  description: Survival analysis method will be applied. Time to chronic GVHD will be defined from time of the last CTL infusion to the onset of chronic GVHD, or the last clinical assessment date if no chronic GVHD. Cumulative incidence of chronic GVHD at 6 and 12 months will be estimated.
  measure: Antiviral activity defined as response to viral load [ Time Frame: 6 weeks ]
  time frame: 6 weeks
  description: Complete response, partial , or no response will be defined and proportion of each outcome will be calculated.
  measure: Rate of anti-CMV response improvement in the peripheral blood of participants [ Time Frame: 6 weeks ]
  time frame: 6 weeks
  description: Anti-CMV response will be measured by ELISpot (IFN-y spots/10e6 cells)
  measure: Clinical response to CTL infusions [ Time Frame: At 6 weeks and 3 months ]
  time frame: 6 weeks and 3 month
  description: In cases with CMV disease, clinical response can be evaluated with evaluation of the involved organ with specific exams (if required) as computed tomography, colonoscopy, eye fundus examination and biopsy .
  arm group label: Lymphocyte infusion
  arm group type: Experimental
  description: Patients with CMV disease or reactivation will be included for receiving donor-CMV-specific cells
  intervention type: Combination Product
  intervention name: Lymphocyte infusion (ImmuneCellVir-I)
  description: Infusion of donor CMV specific cells into patients eligible to the trial
  arm group label: Lymphocyte infusion
  other name: CMV-specific cells infusion
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Nelson Hamerschlak, MD, PhD
  role: Principal Investigator
  affiliation: Hospital Israelita Albert Einstein
  last name: Nelson C Hamerschlak, MD, PhD
  phone: +5511999614340
  email: hamer@einstein.br
  last name: Luciana C Marti, PhD
  phone: +5511983716733
  email: luciana.marti@einstein.br
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: Brazil
  responsible party type: Sponsor
  mesh term: Viremia