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Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01199562
Recruitment Status : Completed
First Posted : September 13, 2010
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:

RATIONALE: Infection prophylaxis and management may help prevent cytomegalovirus (CMV) infection caused by a stem cell transplant.

PURPOSE:This clinical trial studies infection prophylaxis and management in treating cytomegalovirus infection in patients with hematologic malignancies previously treated with donor stem cell transplant.


Condition or disease Intervention/treatment
Hematopoietic/Lymphoid Cancer Accelerated Phase Chronic Myelogenous Leukemia Acute Undifferentiated Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Grade III Lymphomatoid Granulomatosis Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Aplastic Anemia Atypical Chronic Myeloid Leukemia, BCR-ABL Negative Blastic Phase Chronic Myelogenous Leukemia Chronic Eosinophilic Leukemia Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Chronic Phase Chronic Myelogenous Leukemia Contiguous Stage II Adult Burkitt Lymphoma Contiguous Stage II Adult Diffuse Large Cell Lymphoma Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma Contiguous Stage II Adult Lymphoblastic Lymphoma Contiguous Stage II Grade 1 Follicular Lymphoma Contiguous Stage II Grade 2 Follicular Lymphoma Contiguous Stage II Grade 3 Follicular Lymphoma Contiguous Stage II Mantle Cell Lymphoma Contiguous Stage II Marginal Zone Lymphoma Contiguous Stage II Small Lymphocytic Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Cytomegalovirus Infection de Novo Myelodysplastic Syndromes Essential Thrombocythemia Extramedullary Plasmacytoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Intraocular Lymphoma Isolated Plasmacytoma of Bone Mast Cell Leukemia Meningeal Chronic Myelogenous Leukemia Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Burkitt Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma Noncontiguous Stage II Adult Lymphoblastic Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Polycythemia Vera Post-transplant Lymphoproliferative Disorder Previously Treated Myelodysplastic Syndromes Primary Myelofibrosis Primary Systemic Amyloidosis Progressive Hairy Cell Leukemia, Initial Treatment Prolymphocytic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia 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 Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Secondary Myelofibrosis Splenic Marginal Zone Lymphoma Stage 0 Chronic Lymphocytic Leukemia Stage I Adult Burkitt Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage I Adult Diffuse Mixed Cell Lymphoma Stage I Adult Diffuse Small Cleaved Cell Lymphoma Stage I Adult Hodgkin Lymphoma Stage I Adult Immunoblastic Large Cell Lymphoma Stage I Adult Lymphoblastic Lymphoma Stage I Adult T-cell Leukemia/Lymphoma Stage I Chronic Lymphocytic Leukemia Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Grade 3 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Marginal Zone Lymphoma Stage I Multiple Myeloma Stage I Mycosis Fungoides/Sezary Syndrome Stage I Small Lymphocytic Lymphoma Stage II Adult Hodgkin Lymphoma Stage II Adult T-cell Leukemia/Lymphoma Stage II Chronic Lymphocytic Leukemia Stage II Cutaneous T-cell Non-Hodgkin Lymphoma Stage II Multiple Myeloma Stage II Mycosis Fungoides/Sezary Syndrome 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 Hodgkin Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Adult T-cell Leukemia/Lymphoma Stage III Chronic Lymphocytic Leukemia Stage III Cutaneous T-cell Non-Hodgkin 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 Multiple Myeloma Stage III Mycosis Fungoides/Sezary Syndrome 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 Hodgkin Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Adult T-cell Leukemia/Lymphoma Stage IV Chronic Lymphocytic Leukemia Stage IV Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome Stage IV Small Lymphocytic Lymphoma T-cell Large Granular Lymphocyte Leukemia Waldenstrom Macroglobulinemia Procedure: infection prophylaxis and management Other: laboratory biomarker analysis Other: flow cytometry Genetic: DNA analysis Genetic: RNA analysis Procedure: management of therapy complications Drug: ganciclovir Drug: valganciclovir Drug: foscarnet sodium Procedure: antiviral therapy Genetic: polymerase chain reaction Genetic: protein expression analysis

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy and safety of a individualized strategy for cytomegalovirus (CMV) preemptive management, one that monitors CMV viral load and clinical markers of immunosuppression to optimize use of ganciclovir in recipients of allogeneic hematopoietic cell transplantation (HCT) who experience CMV reactivation.

SECONDARY OBJECTIVES:

I. To investigate how donor killer-cell immunoglobulin-like receptors (KIR) genes of interest (activating KIR2DS2 and 2DS4, inhibitory KIR2DL1, 2DL2/2DL3, 3DL1, 3DL2), together with their recipient ligands where known, influence CMV reactivation-free survival after allogeneic HCT, independently of clinical risk factors such as onset of acute graft-versus-host disease.

II. To investigate whether markers of natural killer (NK) cell function correlate with a) KIR/ligand compound genotype and baseline or concurrent clinical factors and b) with history of CMV reactivation and anti-CMV therapy at the time of NK cell collection.

III. To investigate associations between NK cell recovery and antigen-specific T cell immune reconstruction.

OUTLINE: Patients receive standard antiviral infection prophylaxis and management comprising ganciclovir, valganciclovir, or foscarnet sodium for 2 weeks or until the plasma CMV deoxyribonucleic acid (DNA) quantitative polymerase chain reaction (Q-PCR) is negative. Patients may receive additional courses based on subsequent CMV reactivations.

After completion of study treatment, patients are followed up for up to 1 year.

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Study Type : Observational
Actual Enrollment : 153 participants
Official Title: Modified Preemptive CMV Management Strategy After Allogeneic Hematopoietic Cell Transplantation and Laboratory Correlation With Innate Immune Function
Study Start Date : December 2010
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Lymphosarcoma B-cell Lymphoma Follicular Lymphoma Diffuse Large B-Cell Lymphoma Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Marginal Zone Lymphoma Chronic Myeloproliferative Disorders Myelodysplastic Syndromes Cutaneous T-cell Lymphoma Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Chronic Lymphocytic Leukemia Multiple Myeloma AL Amyloidosis Mantle Cell Lymphoma Peripheral T-cell Lymphoma Extranodal Nasal NK/T Cell Lymphoma Hodgkin Lymphoma Acute Graft Versus Host Disease Anaplastic Large Cell Lymphoma Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Cytomegalic Inclusion Disease Primary Myelofibrosis Aplastic Anemia Waldenstrom Macroglobulinemia Polycythemia Vera Burkitt Lymphoma Chronic Graft Versus Host Disease Post-transplant Lymphoproliferative Disease Mycosis Fungoides Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Hairy Cell Leukemia Aggressive NK Cell Leukemia T-cell Large Granular Lymphocyte Leukemia Myelodysplastic/myeloproliferative Disease Adult T-cell Leukemia/lymphoma Essential Thrombocythemia Sezary Syndrome Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Plasmacytoma Chronic Neutrophilic Leukemia Leukemia, T-cell, Chronic Lymphomatoid Granulomatosis Hypereosinophilic Syndrome Mastocytosis

Group/Cohort Intervention/treatment
Arm I
Patients receive standard antiviral infection prophylaxis and management comprising ganciclovir, valganciclovir, or foscarnet sodium for 2 weeks or until the plasma CMV DNA Q-PCR is negative. Patients may receive additional courses based on subsequent CMV reactivations.
Procedure: infection prophylaxis and management
Undergo infection prophylaxis and management
Other Name: treatment of infectious disease

Other: laboratory biomarker analysis
Correlative studies

Other: flow cytometry
Correlative studies

Genetic: DNA analysis
Correlative studies

Genetic: RNA analysis
Correlative studies

Procedure: management of therapy complications
undergo infection prophylaxis and management
Other Name: complications of therapy, management of

Drug: ganciclovir
Given IV
Other Names:
  • BW 759U
  • BW-B759U

Drug: valganciclovir
Given orally
Other Names:
  • Valcyte
  • VGCV

Drug: foscarnet sodium
Given orally
Other Names:
  • Foscavir
  • trisodium phosphonoformate

Procedure: antiviral therapy
undergo infection prophylaxis and management
Other Name: therapy, antiviral

Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR

Genetic: protein expression analysis
Correlative studies




Primary Outcome Measures :
  1. Initiation of anti-CMV therapy [ Time Frame: Day 80 post stem cell transplant ]
    Subjects will not be considered treated with anti-CMV agents unless at least 4 consecutive days of therapy are completed.

  2. Diagnosis of CMV pneumonia [ Time Frame: 1 year ]
    Confirmed by detection of CMV in bronchoalveolar lavage or lung biopsy. Reported overall and separately for those whose preemptive management was and was not modified (postponed or foregone or limited to a false start) and compared to corresponding incidence in a similar cohort at our institution.


Secondary Outcome Measures :
  1. CMV reactivation-free survival, monitored using a real time PCR assay for CMV DNA in plasma [ Time Frame: Up to day 100 post-transplant ]
    Modeled using proportional hazards regression. Primary risk factors will be donor KIR of interest (activating KIR2DS2 and 2DS4, inhibitory KIR2DL1, 2DL2/2DL3, 3DL1, 3DL2), together with their recipient ligands where known. Potential confounding factors to be controlled in the model will include established clinical risk factors, including pretransplant CMV serostatus of donor and recipient, unrelated donor, marrow versus peripheral blood stem cells, and onset of acute graft-versus-host disease, handled as a time-dependent variable. The proportionality of hazards over time will be verified.

  2. Percent cytotoxicity and ex vivo percent CD56+/CD107B+ cells [ Time Frame: Day 120 post stem cell transplant ]
    Studied longitudinally in generalized linear models. Each of the 2 markers of NK function will be modeled separately.



Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis: hematologic malignancies/disorders including aplastic anemia and myelodysplastic syndrome
  • Procedure: first allogeneic, T cell-replete transplantation of stem-cells from peripheral blood or bone marrow of an human leukocyte antigen (HLA) matched, unrelated or nonsyngeneic sibling donor
  • CMV seropositive donor and/or recipient
  • Performance level: must have already been determined to be eligible for HCT at City of Hope (COH)
  • Organ function requirements: The minimum organ function requirements should be the same as the requirements for HCT
  • Informed Consent: All patients must be capable of signing a written informed consent and no consent can be provided by a legal guardian

Exclusion Criteria:

  • The recipient had prior polymerase chain reaction (PCR) positive CMV infection in blood or organ-specific disease in the past 12 months
  • The source of hematopoietic stem cells is T-cell depleted
  • Concomitant anti-graft-versus-host disease (GVD) treatment includes in vivo T cell depletion
  • Recipient is human immunodeficiency virus (HIV)-1 positive
  • No prior allogeneic HCT (Allo HCT) (autologous HCT [Auto HCT] is allowed)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01199562


Locations
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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ryotaro Nakamura City of Hope Medical Center
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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01199562    
Other Study ID Numbers: 09038
NCI-2010-01932
First Posted: September 13, 2010    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: November 2017
Additional relevant MeSH terms:
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Infections
Burkitt Lymphoma
Mycoses
Cytomegalovirus Infections
Lymphoma
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Lymphoma, Follicular
Preleukemia
Lymphoma, Non-Hodgkin
Neoplasm Metastasis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, Mantle-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma, B-Cell, Marginal Zone
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Mycosis Fungoides
Sezary Syndrome
Leukemia, T-Cell