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

December 17, 2013 updated by: Milton S. Hershey Medical Center

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Cancer Institute at Milton S. Hershey Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Safety

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Milton S. Hershey Medical Center

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2008

Primary Completion (ANTICIPATED)

August 1, 2014

Study Registration Dates

First Submitted

October 8, 2008

First Submitted That Met QC Criteria

October 8, 2008

First Posted (ESTIMATE)

October 9, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

December 18, 2013

Last Update Submitted That Met QC Criteria

December 17, 2013

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000615167
  • PSCI-PSHCI-08-051

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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