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

Sponsor

Milton S. Hershey Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT00769613

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Biological: cytomegalovirus IE-1-specific cytotoxic T lymphocytes Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes Biological: therapeutic allogeneic lymphocytes Genetic: polymerase chain reaction Other: flow cytometry Other: immunological diagnostic method Other: laboratory biomarker analysis	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Emergency Access to C.V. pp65 / IE-1 Specific Cytotoxic T Lymphocytes for Recipients of Allogeneic Stem Cell Transplants With Persistant or Therapy Refractory Infections

Study Start Date :

Aug 1, 2008

Anticipated Primary Completion Date :

Aug 1, 2014

Outcome Measures

Primary Outcome Measures

Safety []
Toxicity []

Secondary Outcome Measures

Time to development of cytomegalovirus (CMV)-specific immune reconstitution []
CMV DNA levels []
Time during post-infusion follow-up at which the dominant CMV pp65- and IE-1 epitopes for the donor is recognized by the cytotoxic T-cell lymphocytes (CTL) []
Feasibility of CMV pp65- and IE-1 CTL culture after CMV vaccination of seronegative donors []

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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