Clinical Trials /

T Cell Therapy of Opportunistic Cytomegalovirus Infection

NCT02982902

Description:

The purpose of this study is to determine if a specific type of cell-based immunotherapy, using T-cells from a donor that are specific against cytomegalovirus (CMV) is feasible to treat infections by CMV. Adoptive T-cell therapy is an investigational (experimental) therapy that works by using the blood of a donor and selecting the T-cells that can respond against a specific infectious entity. These selected T-cells are then infused to the patient, to try to give the immune system the ability to fight the infection. Adoptive T-cell therapy is experimental because it is not approved by the Food and Drug Administration (FDA).

Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: T Cell Therapy of Opportunistic Cytomegalovirus Infection
  • Official Title: Antigen Specific Adoptive T Cell Therapy for Opportunistic Cytomegalovirus Infection Occurring After Stem Cell Transplant

Clinical Trial IDs

  • ORG STUDY ID: CASE1Z16
  • NCT ID: NCT02982902

Conditions

  • Cytomegalovirus Infections
  • Hematopoietic Stem Cell Transplant
  • Opportunistic Infections

Interventions

DrugSynonymsArms
CMV specific adoptive t-cellsimmunotherapyCMV specific adoptive t-cells

Purpose

The purpose of this study is to determine if a specific type of cell-based immunotherapy, using T-cells from a donor that are specific against cytomegalovirus (CMV) is feasible to treat infections by CMV. Adoptive T-cell therapy is an investigational (experimental) therapy that works by using the blood of a donor and selecting the T-cells that can respond against a specific infectious entity. These selected T-cells are then infused to the patient, to try to give the immune system the ability to fight the infection. Adoptive T-cell therapy is experimental because it is not approved by the Food and Drug Administration (FDA).

Detailed Description

      The primary objective of this study is to determine the feasibility of the treatment of
      opportunistic cytomegalovirus (CMV) infections after hematopoietic stem cell transplant
      (HSCT) with virus-specific, antigen-selected T-cells, selected using the CliniMACS prodigy
      system.

      Secondary Objective(s)

        -  To describe the safety profile of the infusion of CMV- specific, antigen selected
           T-cells.

        -  To describe the toxicities related to infusion of CMV- specific, antigen selected
           T-cells.

        -  To describe the rate of eradication of opportunistic CMV infections after HSCT and and
           treatment with CMV-specific, antigen-selected T-cells using the CliniMACS Prodigy
           System.

      This feasibility study will include a single treatment cohort.
    

Trial Arms

NameTypeDescriptionInterventions
CMV specific adoptive t-cellsExperimentalThis study involves a one-time infusion of the experimental CMV specific adoptive t-cells. After this infusion, patients will be followed for 4 weeks.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must have received allogeneic hematopoietic stem cell transplant and be
                 greater than 30 days post-transplant at the time of registration
    
              -  Patients must have documented opportunistic CMV infection, or reactivation; the
                 criteria include (both of the following criteria must be met)
    
                   -  Patients may have asymptomatic viremia (>1000 copies/ml) OR presence of symptoms
                      secondary to CMV infection, AND
    
                   -  Patients must have ONE OF THE NEXT FOUR CRITERIA:
    
                        -  Absence of an improvement of viral load after ≥ 14 days of antiviral
                           therapy with ganciclovir, valganciclovir or foscarnet (decrease by at least
                           1 log, i.e. 10-fold) or
    
                        -  New, persistent and/or worsening CMV-related symptoms, signs and/or markers
                           of end organ compromise while on antiviral therapy with ganciclovir,
                           valganciclovir or foscarnet, or
    
                        -  Have contraindications or experience adverse effects of antiviral therapy
                           with ganciclovir, valganciclovir or foscarnet.
    
                        -  Second recurrence of CMV viremia, CMV-related symptoms, signs and/or
                           markers of end organ compromise.
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
    
              -  Women of child-bearing potential and men must agree to use adequate contraception
                 (double barrier method of birth control or abstinence) 4 weeks prior to study entry,
                 for the duration of study participation and for 3 months after completing treatment.
    
              -  Subjects must have the ability to understand and the willingness to sign a written
                 informed consent document, or assent document.
    
            Exclusion Criteria:
    
              -  Pregnant or breastfeeding women are excluded from this study.
    
              -  Patients with opportunistic viral infections other than CMV.
    
              -  Patients with active, grade 2-4, acute graft vs. host disease (GVHD), chronic GVHD or
                 any condition requiring high doses of glucocorticosteroid (>0.5 mg/kg/day prednisone
                 or its equivalent) as treatment
    
              -  Treatment with antithymocyte globulin within 28 days of planned infusion of virus -
                 specific, antigen selected T cells.
    
              -  Treatment with virus - specific T cells within 6 weeks (42 days) of planned infusion.
    
            Donor eligibility
    
              -  Related donor of T cells must be at least partially HLA compatible, matching with
                 recipient in at least 3/6 HLA loci (HLA-A, HLA-B, and HLA-DRB1 loci will be
                 considered for this).
    
              -  Must have evidence of a serologic response (i.e. be seropositive) against CMV.
    
              -  Age ≥ 18 years
    
              -  Must meet the criteria for donor selection defined in the Standard Operating
                 Procedures of University Hospitals Seidman Cancer Center Stem Cell Transplant Program
    
              -  Must be capable of undergoing a single standard 2 blood volume leukapheresis or
                 donation of one unit of whole blood
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:3 Months
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence of adverse events
    Time Frame:Up to 100 days after transplant
    Safety Issue:
    Description:To determine the feasibility of the intervention, the study will record the incidence of adverse events, including graft versus host disease and other complications will be evaluated using binomial distribution theory and their 95% confidence intervals (CIs) will be also estimated using Wilson's method

    Secondary Outcome Measures

    Measure:Eradication rate of opportunistic CMV infections
    Time Frame:Up to 100 days after transplant
    Safety Issue:
    Description:The eradication rate will be the disappearance of opportunistic CMV infections with the use of CMV-specific, antigen-selected T cells using the CliniMACS Prodigy System over the total number CMV infections.
    Measure:response rate
    Time Frame:Up to 100 days after transplant
    Safety Issue:
    Description:A response rate of 25% is considered unacceptable; and the anticipated response rate is approximately 55% for the study population using the cell therapy.

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Case Comprehensive Cancer Center

    Trial Keywords

    • Immunotherapy
    • T-Cell Therapy
    • Lymphoproliferative Disorder

    Last Updated

    February 2, 2017