T Cell Therapy of Opportunistic Cytomegalovirus Infection

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.

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