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

Cancer Clinical Trial

Official title:

A Phase I Trial to Examine the Safety, Clinical, Immunologic and Virologic Effects of CMV pp65 Specific Cytotoxic T Lymphocytes for Recipients of Allogeneic Stem Cell Transplants With Persistent or Therapy Refractory Infections

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00509691
• Other study ID #: CDR0000557037
• Secondary ID: PSCI-25114
• Status: Completed
• Phase: Phase 1
• First received: July 30, 2007
• Last updated: May 8, 2017
• Start date: June 2007
• Est. completion date: December 2011

Study information

• Verified date: May 2017
• Source: University of Louisville
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Cytomegalovirus Infections
• Infection

Intervention

Biological:
• cytomegalovirus pp65-specific cytotoxic T lymphocytes

Genetic:
• polymerase chain reaction

Other:
• diagnostic laboratory biomarker analysis

• flow cytometry

• immunologic technique

Locations

Country	Name	City	State
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Louisville	Penn State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity		1 year
Primary	Treatment failure		1 year
Primary	Safety		1 year
Secondary	Time to development of cytomegalovirus (CMV) specific immune reconstitution		1 year
Secondary	CMV DNA levels		1 year
Secondary	Time during post-infusion follow up at which the dominant CMV pp65 epitope for the donor is recognized by the cytotoxic t-cell lymphocyte recipient		1 year