Treatment of Cytomegalovirus (CMV) Infections With Viral-Specific T Cells

Inclusion Criteria:

1. Adult or pediatric patient suffering from CMV reactivation/infections following HSCTor due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxictherapy).

• CMV reactivation/viremia defined as positive (>500 copies/ml) CMV qPCR and/or

• Presence of symptoms secondary to CMV infection or evidence of invasive CMVinfection (e.g. pneumonitis, colitis) AND

• Patients must have ONE OF THE FOLLOWING CRITERIA:

• Absence of an improvement of viral load after ≥ 14 days of antiviraltherapy with ganciclovir, valganciclovir or foscarnet (decrease by atleast 1 log, i.e. 10-fold), or

• New, persistent and/or worsening CMV-related symptoms, signs and/ormarkers of end organ compromise while on antiviral therapy withganciclovir, valganciclovir or foscarnet, or

• Have contraindications or experience adverse effects of antiviral therapywith ganciclovir, valganciclovir or foscarnet, or

• Known resistance to ganciclovir and/or foscarnet based on moleculartesting.

2. Recipients of an allogeneic HSCT must be 28 days after stem cell infusion at thetime of T-cell transfer.

3. Written informed consent given by patient or legal representative.

4. Minimum patient age 1 month.

5. Minimum weight 7 lbs.

6. Female patients of childbearing age with negative pregnancy tests.

7. Patient Karnofsky/Lansky Performance Status >30%.

8. Donor eligible based on FACT infectious screening requirements.

Exclusion Criteria:

1. Patient with acute GVHD > grade 2 or active moderate or severe chronic GVHD at timeof T-cell transfer

2. Patient receiving steroids (>1.0 mg/kg body weight (BW) prednisone equivalent) atthe time of T-cell transfer

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

4. Patient treated with donor lymphocyte infusion (DLI) within 28 days prior to T-celltransfer

5. Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressivemonoclonal antibodies within 28 days.

6. Patient with organ dysfunction or failure as determined by Karnofsky (patients >16years) or Lansky (patients ≤16 years) score ≤30% (Appendix 5)

7. Patients with CMV retinitis

8. Concomitant enrollment in another clinical trial with endpoints interfering withthis study

9. Any medical condition which could compromise participation in the study according tothe investigator's assessment

10. Known HIV infection

11. Female patient who is pregnant or breast-feeding, or adult of reproductive potentialnot willing to use an effective method of birth control during study treatment.Note: Women of childbearing potential must have a negative serum pregnancy test atstudy entry.

12. Patients unwilling or unable to comply with the protocol or unable to give informedconsent.

Donor Eligibility:

The original donor will be the first choice as source of T cells. If the original donor is not available for donation (such as NMDP donor, cord blood unit, or related donor not available) of peripheral mononuclear cells or does not meet all donor eligibility criteria (including donor selection criteria based on University of Wisconsin - Madison Standard Operating Procedures for the selection of allogeneic donors), 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).

1. All donors must be ≥ 18 years old, available, CMV IgG positive, eligible and capableof undergoing a single standard 2 blood volume leukapheresis. If original HSCT donoris not available, CMV IgG negative or ineligible, a CMV IgG positive fully matchedor haploidentical family donor will be used.

2. Related donors must be at least partially HLA compatible, matching with recipient inat least 3/6 HLA loci (HLA-A, HLA-B and HLA-DRB1 will be considered for this).

3. Donors must be CMV IgG seropositive.

4. Donors must show CMV T-cell activation after incubation with MACS GMP PepTivatorPeptide Pools of CMV pp65 before undergoing leukapheresis.

5. Donor must meet the criteria for donor selection defined in the Standard OperatingProcedures of the University of Wisconsin Hospitals and Clinics Stem Cell TransplantProgram and in FACT standards.