Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Study Details
Study Description
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.
Detailed Description
PRIMARY OBJECTIVES:
- 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:
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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.
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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.
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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.
Study Design
Arms and Interventions
| Arm | 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 Names:
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 Names:
Drug: ganciclovir
Given IV
Other Names:
Drug: valganciclovir
Given orally
Other Names:
Drug: foscarnet sodium
Given orally
Other Names:
Procedure: antiviral therapy
undergo infection prophylaxis and management
Other Names:
Genetic: polymerase chain reaction
Correlative studies
Other Names:
Genetic: protein expression analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Initiation of anti-CMV therapy [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.
- Diagnosis of CMV pneumonia [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
- CMV reactivation-free survival, monitored using a real time PCR assay for CMV DNA in plasma [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.
- Percent cytotoxicity and ex vivo percent CD56+/CD107B+ cells [Day 120 post stem cell transplant]
Studied longitudinally in generalized linear models. Each of the 2 markers of NK function will be modeled separately.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis: hematologic malignancies/disorders including aplastic anemia and myelodysplastic syndrome
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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
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CMV seropositive donor and/or recipient
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Performance level: must have already been determined to be eligible for HCT at City of Hope (COH)
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Organ function requirements: The minimum organ function requirements should be the same as the requirements for HCT
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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:
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The recipient had prior polymerase chain reaction (PCR) positive CMV infection in blood or organ-specific disease in the past 12 months
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The source of hematopoietic stem cells is T-cell depleted
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Concomitant anti-graft-versus-host disease (GVD) treatment includes in vivo T cell depletion
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Recipient is human immunodeficiency virus (HIV)-1 positive
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No prior allogeneic HCT (Allo HCT) (autologous HCT [Auto HCT] is allowed)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope Medical Center | Duarte | California | United States | 91010 |
Sponsors and Collaborators
- City of Hope Medical Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Ryotaro Nakamura, City of Hope Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 09038
- NCI-2010-01932