Donor Cytomegalovirus-Specific Cytotoxic T-Lymphocytes in Treating Patients With a Persistent Cytomegalovirus Infection

PRIMARY OBJECTIVES:

I. To assess the efficacy, feasibility and safety of administering most closely human
leukocyte antigen (HLA)-matched cytomegalovirus (CMV) specific cytotoxic T-lymphocytes
(HMC-CTLs) generated by "gamma-catch" to mediate antiviral activity in hematopoietic stem
cell transplantation (HSCT) recipients with CMV infections.

SECONDARY OBJECTIVES:

I. To assess the persistency of the administered HMC-CTLs generated by "gamma-catch" and
their contribution immune reconstitution.

OUTLINE:

Patients receive allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes intravenously
(IV). Patients with partial response, stable disease, or progressive disease may receive an
additional dose of allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes at a minimum
of 2 weeks from the first infusion.

After completion of study treatment, patients are followed up periodically for 12 months.

Inclusion Criteria:

- Patients with or without a malignancy; and/or any type of autologous or allogeneic
HSCT; and/or patients who are immunocompromised with CMV infection will be included

- Persistent CMV infection despite optimum anti-viral therapy

- Patients with CMV disease: defined as the demonstration of CMV by biopsy specimen
from visceral sites (by culture or histology) or the detection of CMV by culture
or direct fluorescent antibody stain in bronchoalveolar lavage fluid in the
presence of new or changing pulmonary infiltrates; OR

- Failure of antiviral therapy: defined as the continued presence of
deoxyribonucleic acid (DNA)emia (defined as >= 137 copies/ml by polymerase chain
reaction [PCR]) for at least 2 weeks of CMV antiviral therapy; OR

- Optimum therapy is defined as at least 14 days of therapy with ganciclovir,
foscarnet, cidofovir, or valganciclovir for patients with disease or CMV
viremia

- Relapse while on CMV antiviral therapy defined as recurrence of DNAemia
while being on at least 2 weeks of antiviral therapy OR

- Patients who cannot tolerate standard anti-viral therapy and cannot continue
anti-viral treatment due to side effect profile will be eligible independent of
anti-viral therapy duration

- Clinical status at enrollment to allow tapering of steroids equal to or less than 0.5
mg/kg/day of prednisone

- Patients with chronic graft-versus-host disease (GVHD) if on prednisone equal to or
less than 0.5 mg/kg and not receiving second-line GVHD treatments like pentostatin,
infliximab, etanercept, etc

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

- Negative pregnancy test in female patients of childbearing potential

Exclusion Criteria:

- Patients receiving prednisone > 0.5 mg/kg/day at time of enrollment, or have received
anti-thymocyte globulin (ATG), donor lymphocyte infusion (DLI) or Campath within 28
days of enrollment

- Patients with other uncontrolled infections; for bacterial infections, patients must
be receiving definitive therapy and have no signs of progressing infection for 72
hours prior to enrollment; for fungal infections patients must be receiving definitive
systemic anti-fungal therapy and have no signs of progressing infection for 1 week
prior to enrollment; progressing infection is defined as hemodynamic instability
attributable to sepsis or new symptoms, worsening physical signs or radiographic
findings attributable to infection; persisting fever without other signs or symptoms
will not be interpreted as progressing infection; patients with ongoing viral
infections are excluded

- Patients with active acute GVHD grades II-IV

- Active and uncontrolled relapse of malignancy