Measuring Changes in Blood in Patients at High Risk of Cytomegalovirus Infection After Undergoing Donor Bone Marrow Transplant or Peripheral Blood Stem Cell Transplant

June 3, 2015 updated by: City of Hope Medical Center

CMV Specific Cellular Immunity in Recipients of Allogeneic Bone Marrow Transplantation: Association of CMV-Specific HLA-Peptide Tetramer Binding With Cytotoxic T-Cell Function, CMV Infection and Other Clinical Events

RATIONALE: Tests that measure certain changes in blood in patients at high risk of cytomegalovirus infection may help doctors learn more about predicting cytomegalovirus infection after donor stem cell transplant.

PURPOSE: This clinical trial is studying tests that measure changes in the blood in patients at high risk of cytomegalovirus infection after undergoing donor bone marrow transplant or peripheral stem cell transplant.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • To document the quantitative characteristics of a cytomegalovirus (CMV)-specific HLA-peptide tetramer-binding assay (TBA) for cytotoxic T lymphocytes (CTLs) in patients who have undergone allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT).
  • To confirm the optimal TBA conditions for CTL characterization in these patients.
  • To compare the TBA results for these patients with conventional assays for CTL functions.
  • To compare CMV-specific TBA during the first 3 months after allogeneic BMT or PBSCT and to determine whether this binding function, in either donor or recipient, is a surrogate marker for protection from risk of CMV infection in these patients.
  • To determine whether acquisition of CMV-specific TBA protects from risk for CMV disease in patients having active CMV infection after allogeneic BMT or PBSCT.

OUTLINE: This is a multicenter study. Patients accrue initially to cohort 1 until a sufficient number of stem cell transplantation (SCT) recipients are enrolled. Patients then accrue to cohort 2 based on documented cytomegalovirus (CMV) infection and preemptive treatment with ganciclovir within 90 days after SCT (patients previously accrued to cohort 1 can be accrued to cohort 2 if they develop CMV infection).

  • Cohort 1: Patients undergo blood sample collection on approximately days 40, 90, 120, 150, 180, and 360 post transplantation. Samples are analyzed (to determine the development of CMV immunity) for prevalence of CMV-specific cytotoxic T-lymphocytes (CTL) by HLA-peptide tetramer-binding assay (TBA) pp65, with and without in vitro stimulation (IVS). Samples collected on days 40 and 90 are also analyzed by chromium release assay (CRA). Patients suspected of developing CMV viremia may receive ganciclovir according to standard clinical practice.
  • Cohort 2: Patients undergo blood sample collection on approximately days 90, 120, 150, 180, and 360 after SCT. Samples are analyzed by TBApp65 staining and for prospective measurement of CMV-specific CTL functions.

All patients undergo routine clinical surveillance for CMV infection on days 21 to 100 after SCT. CMV viral load measurements are obtained twice weekly by CMV-DNA PCR assays on blood cells and plasma and shell-vial blood cultures. In cohort 2, CMV viral load is also determined on days 90 (if not previously as part of cohort 1), 120, 150, 180, and 360. The CMV infection data obtained is then compared with TBA and CTL measurements using HLA-specific tetramers and IVS-induced cytotoxicity assays. Clinical events, such as graft-versus-host disease, underlying disease status, and procedure-related complications are also analyzed and correlated with TBA results.

Stromal cell cultures are obtained from marrow donors at the time of marrow harvest for use as target cells in CTL assays. Donor saliva samples are also obtained for detection of CMV infection by shell-vial method.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Meets 1 of the following criteria at the City of Hope National Medical Center:

    • Patient who has undergone a matched-related or matched-unrelated allogeneic bone marrow or peripheral blood stem cell transplantation (SCT) for a hematological malignancy (e.g., aplastic anemia or myelodysplastic syndromes)

      • At risk for cytomegalovirus (CMV) infection and disease due to 1 of the following risk factors:

        • CMV-seropositive prior to transplantation
        • Received SCT from a CMV-seropositive donor
    • Donor for matched-related SCT
    • Healthy volunteer evaluated concurrently with SCT recipients to establish normal values for both CMV-seronegative and CMV-seropositive persons
  • Any HLA serotypes allowed

PATIENT CHARACTERISTICS:

  • See Disease Characteristics

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Quantitative determination of HLA-peptide tetramer-binding assay (TBA) pp65 on days 40 and 90 after stem cell transplantation, with and without in vitro stimulation
Comparison of quantitative determination of TBApp65 with concomitant determination of in vitro CMV-specific cytotoxic T-lymphocyte function on days 40 and 90 after stem cell transplantation
Correlation of TBApp65 results with CMV viral loads
Correlation of TBApp65 results with CMV-associated complications

Secondary Outcome Measures

Outcome Measure
Correlation of TBApp65 results with clinical events, including acute graft-versus-host-disease (GVHD), chronic GVHD, ganciclovir exposure, and survival

Collaborators and Investigators

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

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: John A. Zaia, MD, City of Hope Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

January 1, 2000

Primary Completion (Actual)

July 1, 2007

Study Completion (Actual)

July 1, 2007

Study Registration Dates

First Submitted

July 15, 2008

First Submitted That Met QC Criteria

July 15, 2008

First Posted (Estimate)

July 16, 2008

Study Record Updates

Last Update Posted (Estimate)

June 8, 2015

Last Update Submitted That Met QC Criteria

June 3, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 99061
  • P30CA033572 (U.S. NIH Grant/Contract)
  • R01AI058148 (U.S. NIH Grant/Contract)
  • CHNMC-99061
  • CDR0000600022 (Registry Identifier: NCI PDQ)

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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