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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00716911
• Other study ID #: 99061
• Secondary ID: R01AI058148P30CA
• Status: Completed
• Phase: N/A
• First received: July 15, 2008
• Last updated: June 3, 2015
• Start date: January 2000
• Est. completion date: July 2007

Study information

• Verified date: June 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Cytomegalovirus Infections
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Neoplasms
• Neoplasms, Plasma Cell
• Nonneoplastic Condition
• Plasmacytoma
• Preleukemia

Intervention

Drug:
• ganciclovir

Genetic:
• polymerase chain reaction

Other:
• flow cytometry

• immunologic technique

Procedure:
• allogeneic bone marrow transplantation

• allogeneic hematopoietic stem cell transplantation

• assessment of therapy complications

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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			No
Primary	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			No
Primary	Correlation of TBApp65 results with CMV viral loads			No
Primary	Correlation of TBApp65 results with CMV-associated complications			No
Secondary	Correlation of TBApp65 results with clinical events, including acute graft-versus-host-disease (GVHD), chronic GVHD, ganciclovir exposure, and survival