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

Primary Purpose

Chronic Myeloproliferative Disorders, Leukemia, Lymphoma

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
ganciclovir
polymerase chain reaction
flow cytometry
immunologic technique
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
assessment of therapy complications
peripheral blood stem cell transplantation
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Chronic Myeloproliferative Disorders focused on measuring 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, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, chronic eosinophilic leukemia, chronic neutrophilic leukemia, primary myelofibrosis, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, stage I multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Outcomes

    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
    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

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

    Full Information

    First Posted
    July 15, 2008
    Last Updated
    June 3, 2015
    Sponsor
    City of Hope Medical Center
    Collaborators
    National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00716911
    Brief Title
    Measuring Changes in Blood in Patients at High Risk of Cytomegalovirus Infection After Undergoing Donor Bone Marrow Transplant or Peripheral Blood Stem Cell Transplant
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2000 (undefined)
    Primary Completion Date
    July 2007 (Actual)
    Study Completion Date
    July 2007 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    City of Hope Medical Center
    Collaborators
    National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Nonneoplastic Condition
    Keywords
    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, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, chronic eosinophilic leukemia, chronic neutrophilic leukemia, primary myelofibrosis, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, stage I multiple myeloma

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Not Applicable
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    ganciclovir
    Intervention Type
    Genetic
    Intervention Name(s)
    polymerase chain reaction
    Intervention Type
    Other
    Intervention Name(s)
    flow cytometry
    Intervention Type
    Other
    Intervention Name(s)
    immunologic technique
    Intervention Type
    Procedure
    Intervention Name(s)
    allogeneic bone marrow transplantation
    Intervention Type
    Procedure
    Intervention Name(s)
    allogeneic hematopoietic stem cell transplantation
    Intervention Type
    Procedure
    Intervention Name(s)
    assessment of therapy complications
    Intervention Type
    Procedure
    Intervention Name(s)
    peripheral blood stem cell transplantation
    Primary Outcome Measure Information:
    Title
    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
    Title
    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
    Title
    Correlation of TBApp65 results with CMV viral loads
    Title
    Correlation of TBApp65 results with CMV-associated complications
    Secondary Outcome Measure Information:
    Title
    Correlation of TBApp65 results with clinical events, including acute graft-versus-host-disease (GVHD), chronic GVHD, ganciclovir exposure, and survival

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    John A. Zaia, MD
    Organizational Affiliation
    City of Hope Comprehensive Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    21719601
    Citation
    Lacey SF, La Rosa C, Kaltcheva T, Srivastava T, Seidel A, Zhou W, Rawal R, Hagen K, Krishnan A, Longmate J, Andersson HA, St John L, Bhatia R, Pullarkat V, Forman SJ, Cooper LJ, Molldrem J, Diamond DJ. Characterization of immunologic properties of a second HLA-A2 epitope from a granule protease in CML patients and HLA-A2 transgenic mice. Blood. 2011 Aug 25;118(8):2159-69. doi: 10.1182/blood-2011-04-349951. Epub 2011 Jun 30.
    Results Reference
    derived

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

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