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

This study has been completed.
Sponsor:
Collaborators:
Information provided by:
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00716911
First received: July 15, 2008
Last updated: March 4, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Nonneoplastic Condition
Drug: ganciclovir
Genetic: polymerase chain reaction
Other: flow cytometry
Other: immunologic technique
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: assessment of therapy complications
Procedure: peripheral blood stem cell transplantation

Study Type: Interventional
Study Design: Primary Purpose: Supportive Care
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

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Cytomegalic Inclusion Disease Lymphosarcoma Lymphoma, Small Cleaved-cell, Diffuse Multiple Myeloma Chronic Myeloproliferative Disorders Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Acute Lymphoblastic Leukemia Hodgkin Lymphoma Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic/myeloproliferative Disease Acute Myeloid Leukemia, Adult Follicular Lymphoma B-cell Lymphomas Myelofibrosis Burkitt Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Lymphoblastic Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Hypereosinophilic Syndrome Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Anaplastic Plasmacytoma
U.S. FDA Resources

Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Correlation of TBApp65 results with CMV viral loads [ Designated as safety issue: No ]
  • Correlation of TBApp65 results with CMV-associated complications [ Designated as safety issue: No ]

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

Estimated Enrollment: 100
Study Start Date: January 2000
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00716911

Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: John A. Zaia, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided by City of Hope Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John A. Zaia, City of Hope Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00716911     History of Changes
Other Study ID Numbers: 99061, R01AI058148, P30CA033572, CHNMC-99061, CDR0000600022
Study First Received: July 15, 2008
Last Updated: March 4, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
cytomegalovirus infection
accelerated phase chronic myelogenous leukemia
atypical chronic myeloid leukemia, BCR-ABL negative
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma

Additional relevant MeSH terms:
Neoplasms
Cytomegalovirus Infections
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Lymphoma, Large-Cell, Immunoblastic
Myelodysplastic-Myeloproliferative Diseases
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on August 27, 2014