Donor CMV Specific CTLs in Treating CMV Reactivation or Infection in Participants Who Have Undergone Stem Cell Transplant or Solid Organ Transplant

PRIMARY OBJECTIVE I. Assess the safety and feasibility of administering high-throughput
antigen stimulation/interferon gamma capture system (Miltenyi Biotec, CliniMACS Prodigy
System) generated CMV specific- CTLs from haploidentical donors in transplant patients both
solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) with CMV
infection despite standard therapy.

OUTLINE:

Participants receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes
intravenously (IV). Participants with partial response, may receive up to 2 additional doses
at monthly intervals.

After completion of study treatment, participants are followed up at 1 year.

Inclusion Criteria:

- Patients must have solid organ transplant or have received allogeneic hematopoietic
stem cell transplant and be greater than 30 days post-transplant at the time of
registration.

- Persistent CMV viremia after standard therapy for >= 7 days with or without proven,
probable or possible CMV specific organ involvement.

- Receipt of an allogeneic HCT using bone marrow, peripheral blood, or umbilical cord
stem cells.

- SOT recipients including but not limited to renal, heart, lung, liver, pancreas, small
bowel, and multi-visceral transplants.

- Treatment of reactivation or infection with CMV: Reactivation is defined as detection
of CMV by quantitative polymerase chain reaction (PCR) from the blood. If any patient
develops CMV deoxyribonucleic acid (DNA)emia or has clinical evidence of CMV infection
(defined as the demonstration of CMV by biopsy specimen from visceral sites by culture
or histology) either pre or after CTL infusions, standard treatment with ganciclovir,
valganciclovir, cidofovir and/or foscarnet will be initiated per physician discretion.
Patients may receive CMV CTLs alone for elevated blood viral loads without evidence of
visceral infection.

- Administration of less than or equal to 0.5 mg/kg/day of prednisone or steroid
equivalent.

- Serum creatinine less than 2 x (upper level of normal (ULN).

- Available CMV seropositive haploidentical donor who is without evidence infection that
would otherwise preclude donation.

- Negative pregnancy test in female patients if applicable (childbearing potential who
have received a reduced intensity conditioning regimen).

- Written informed consent and/or signed assent line from patient, parent or guardian.

- DONOR: Donors will be deemed eligible if they are haploidentical matched to the
patient and are CMV seropositive, defined as detection of serum CMV IgG. Donor will be
screened and determined if acceptable as determined by the full donor evaluation and
transplant physician evaluation.

Exclusion Criteria:

- Receipt of anti-thymocyte globulin (ATG), alemtuzumab, or other T-cell depleting
agents within 28 days of screening for enrollment.

- Receiving > 0.5mg/kg/day of prednisone or steroid equivalent at the time of
enrollment.

- Evidence of uncontrolled infection as follows:

- Bacterial infections - patients must be receiving definitive therapy and have no
signs of progressing infection for 72 hours prior to enrollment.

- Fungal infections - patients must be receiving definitive systemic anti-fungal
therapy and have no signs of progressing infection for 1 week prior to
enrollment.

- Patients with hemodynamic instability attributable to bacterial sepsis or new
symptoms, worsening physical signs or radiographic findings attributable to
concomitant bacterial or fungal infection are excluded. Patients who require
ventilator support for CMV pneumonitis are not excluded. Persisting fever without
other signs or symptoms will not be interpreted as progressing infection.

- Receipt of donor lymphocyte infusion (DLI) within 28 days.

- Patients with active acute graft versus host disease (GvHD) grades II-IV requiring >
0.5 mg/kg/day of prednisone or steroid equivalent or T-cell depleting
immunosuppression.

- Acute graft rejection in solid organ transplantation requiring augmented
immunosuppression with T-cell depleting agents or steroids as mentioned above.

- Active and uncontrolled relapse of malignancy.