Title
Treatment of CMV Infections with Viral-Specific T Cells Against CMV in Pediatric and Adult Immunocompromised Patients or Recipients of Allogeneic Stem Cell Transplantation

Description
Pilot study for treatment of CMV infections with Viral-Specific T Cells

Objective
The purpose of this study is to determine if it is possible to treat your CMV infection with a new type of cell-based immunotherapy(therapy that uses cells of the immune system to treat the infection) and learn about the side effects(unwanted effects) of this therapy. This treatment is called adoptive T cell therapy. Another purpose is to learn how effective those T cells are in clearing your viral infection and how your immune system responds to it.

Adoptive T cell therapy is an investigational (experimental) therapy that works by using the blood of a donor that has immunity(defense) against the CMV virus. The donor cells are collected and then specific cells, called T cells, that are capable of defending you against CMV, are selected out. This is done in a special laboratory at the University of Wisconsin. These selected T cells are then given to you through an IV, similar to how you get a blood transfusion. We hope this will give your immune system the ability to fight the CMV infection but this cannot be guaranteed. This therapy has already been used as part of clinical studies in other research subjects. Because it is not approved by the food and drug administration (FDA), adopitve T cell therapy is considered experimental

Each subject will have one donor in this study. The donor may be your previous stem cell transplant donor or another blood relative. Donor selection depends on several factors, including the donor's immunity to CMV, how closely the genes on white blood cells(called "human leukocyte antigens" or HLA for short) match between patient and donor, health screening factors, ability to produce CMV specific T-cell(immune cells) and donor availability

Treatment Patient and donor are screened for eligibility, if eligible they will be enrolled, 7 days prior to donors leukapheresis patient must still meet eligibility requirements including persistent CMV, if the requirements are met the leukapheresis is preformed and cells are manufactured, then the patient receives the cell infusion and follow-up per protocol requirements

Key Eligibility
Adult or pediatric patient suffering from CMV reactivation/infections following HSCT or due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxic therapy: CMV reactivation/viremia defined as positive (>500 copies/ml) CMV qPCR and/or Presence of symptoms secondary to CMV infection or evidence of invasive CMV infection (e.g. pneumonitis, colitis) AND

Patients must have ONE OF THE FOLLOWING 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
o Have contraindications or experience adverse effects of antiviral therapy with ganciclovir, valganciclovir or foscarnet, or Known resistance to ganciclovir and/or foscarnet based on molecular testing

Recipients of an allogeneic HSCT must be 28 days after stem cell infusion at the time of T-cell transfer

Minimum patient age 1 month and minimum weight 7 lbs

Female patients of childbearing age with negative pregnancy test

Patient Karnofsky/Lansky Performance Status greater than 30%

Donor eligible based on FACT infectious screening requirements

EXCLUSION

Patient with acute GVHD greater than grade 2 or active moderate or severe chronic GVHD at time of T-cell transfer

Patient receiving steroids (greater than 0.5 mg/kg body weight (BW) prednisone equivalent) at the time of T-cell transfer

Patient with organ dysfunction or failure as determined by Karnofsky (patients greater than 16 years) or Lansky (patients less than or equal to 16 years) score less than or equal to 30%

Patients with CMV retinitis

Known HIV infection

Female patient who is pregnant or breast-feeding, or adult of reproductive potential not willing to use an effective method of birth control during study treatment

Patient received allogeneic HSCT less than 28 days prior to T-cell transfer

Patient treated with donor lymphocyte infusion (DLI) within 28 days prior to T-cell transfer

Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressive monoclonal antibodies within 28 days

DONOR ELIGIBILITY

The original donor will be the first choice as source of T cells, If the original donor is not available for donation of peripheral mononuclear cells or does not meet all donor eligibility criteria alternative related donors will be selected, with preference for those who have full HLA matching in 6/6 loci over those with partial HLA matching (≥ 3/6 HLA loci)

All donors must be greater than 18 years old, available, CMV IgG positive, eligible and capable of undergoing a single standard 2 blood volume leukapheresis

Donors must be CMV IgG seropositive

Donors must show CMV T-cell activation after incubation with MACS GMP PepTivator Peptide Pools of CMV pp65 before undergoing leukapheresis

If donor fails to meet any of the inclusion criteria, they will not be eligible to participate in the study

Applicable Disease Sites
Unknown Sites

Participating Institutions
UW Health University Hospital