Emergency Use of Donor Lymphocytes in Treating Patients Who Have Undergone Donor Stem Cell Transplant and Have Cytomegalovirus Infections

Penn State Health

Status and phase: Unknown; Phase 1

Conditions: Cancer

Treatments: Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes; Other: laboratory biomarker analysis; Genetic: polymerase chain reaction; Other: flow cytometry; Other: immunological diagnostic method; Biological: therapeutic allogeneic lymphocytes; Biological: cytomegalovirus IE-1-specific cytotoxic T lymphocytes

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00769613

CDR0000615167

PSCI-PSHCI-08-051

Details and patient eligibility

About

RATIONALE: White blood cells that have been treated in the laboratory may kill cells that are infected with cytomegalovirus.

PURPOSE: This phase I trial is studying how well cytotoxic T cells work in treating patients who have undergone donor stem cell transplant and have cytomegalovirus infections.

Full description

OBJECTIVES:

Primary

• To provide access to cytomegalovirus (CMV) pp65- and IE-1-specific cytotoxic T lymphocytes (CTL) in patients with persistent CMV infections after allogeneic stem cell transplantation.

Secondary

• To characterize CMV pp65- and IE-1-specific immune responses in terms of cytotoxicity and cytokine production pre-infusion and then periodically thereafter.
• To characterize the levels of CMV DNA in recipients of CMV pp65- and IE-1-specific CTL and observe whether the CTL infusion has any impact on level of virus.
• To determine the feasibility of CMV CTL culture from CMV-seronegative donors who have received a CMV vaccine.

OUTLINE: This is a multicenter study.

Patients receive allogeneic cytomegalovirus (CMV) pp65- and IE-1-specific cytotoxic T-cell lymphocytes infusion over 5 minutes on day 1. Patients may receive up to 2 more doses at least 2 weeks after previous dose.

Blood samples are collected and analyzed by quantitative CMV PCR, chromium-release assays for CMV pp65- and IE-1-specific cytotoxicity, and immunophenotype for CD3, CD4, CD8, CD56, CD19, and CD45RA/RO. Intracellular cytofluorometry is used to assess IL-2, IL-4, IL-10, and IFN-γ production by CD4 and CD8 CMV-specific effector cells.

After completion of study therapy, patients are followed periodically for up to 1 year.

Enrollment: 20 estimated patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Recipient of an allogeneic stem cell transplantation

• Cytomegalovirus (CMV)-seropositive and meeting 1 of the following criteria:

  • Patient has a history of CMV antigenemia for ≥ 2 weeks
  • CMV DNA levels ≥ 600 copies/mcg of DNA despite antiviral therapy targeting CMV (e.g., ganciclovir or foscarnet)

• No ongoing graft-vs-host disease

• Has donor available for peripheral blood mononuclear cell collection (for cytotoxic T lymphocytes production), meeting either of the following criteria:

  • CMV-seropositive donor (≥ 2 years of age)
  • CMV-seronegative related donor (≥ 18 years of age) who consents to receive the CMV vaccine

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-3 OR Lansky PS 50-100% (for patients < 16 years of age)
• Bilirubin < 2.0 mg/dL
• AST and ALT < 2.5 times normal
• Creatinine clearance ≥ 30 mL/min
• Pulse oximetry ≥ 94% on no more than 40% oxygen by face mask
• Not moribund
• No patients expected to survive ≤ 1 month after the T-cell infusion due to cardiac, pulmonary, renal, hepatic, or neurologic dysfunction

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Must be on ≤ 1 mg/kg/day of prednisone or its equivalent at the time of study CTL infusion