Vaccine Therapy in Treating Patients Who Have Undergone a Donor Stem Cell Transplant and Have Cytomegalovirus Infection That Has Not Responded to Therapy

University of Louisville (UOFL)

Status and phase: Completed; Phase 1

Conditions: Cancer

Treatments: Other: flow cytometry; Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes; Genetic: polymerase chain reaction; Other: diagnostic laboratory biomarker analysis; Other: immunologic technique

Study type: Interventional

Funder types: Other

Identifiers

NCT00509691

PSCI-25114

CDR0000557037

Details and patient eligibility

About

RATIONALE: Vaccines may help the body build an effective immune response to kill cytomegalovirus infections.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients who have undergone a donor stem cell transplant and have cytomegalovirus infection that has not responded to therapy.

Full description

OBJECTIVES:

Primary

• To determine the safety of infusing cytomegalovirus (CMV) pp65-specific cytotoxic T-lymphocytes (CTL) generated using pp65 peptides in patients who have undergone allogeneic stem cell transplantation and have persistent CMV infections.

Secondary

• Characterize CMV pp65-specific immune responses in terms of cytotoxicity and cytokine production pre-infusion and then periodically thereafter.
• Characterize the levels of CMV DNA in recipients of CMV pp65 CTL and observe whether the CTL infusion has any impact on the level of virus.

OUTLINE: This is a multicenter study.

Patients receive cytomegalovirus (CMV) pp65 cytotoxic T-cell infusion 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-specific cytotoxicity, and immunophenotype for CD3, CD4, CD8, CD56, CD19, and CD45 RA/RD. 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 treatment, patients are followed periodically for up to 1 year.

Enrollment: 20 patients

Sex: All

Ages: 2 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Cytomegalovirus (CMV) seropositive

  • Patient has had CMV antigenemia for ≥ 2 weeks OR CMV DNA levels ≥ 600 copies/μg of DNA despite antiviral therapy targeting CMV (ganciclovir or foscarnet)

• No prior allogeneic stem cell transplantation before the most recent transplantation

• CMV seropositive donor negative for HIV-1, HIV-2, HTLV-1/2 available

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2 (for patients ≤ 16 years of age) OR Lansky performance status 70-100%
• Bilirubin < 2.0 mg/dL
• AST and ALT < 2.5 times upper limit of normal
• Creatinine clearance > 50 mL/min
• Pulse oximetry > 95% without supplemental oxygen
• No history of graft-vs-host disease (GVHD) ≥ grade 2
• Not moribund
• No patients not expected to survive 1 month after T cell infusion due to cardiac, pulmonary, renal, hepatic, or neurologic dysfunction

PRIOR CONCURRENT THERAPY:

• No concurrent systemic immunosuppressive agents for the treatment of GVHD

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Single arm study

Experimental group

Treatment:

Other: diagnostic laboratory biomarker analysis

Genetic: polymerase chain reaction

Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes

Other: flow cytometry

Other: immunologic technique