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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Modified Preemptive CMV Management Strategy After Allogeneic Hematopoietic Cell Transplantation and Laboratory Correlation With Innate Immune Function

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 Summary:

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.

Current Primary Outcome:

• 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.
• 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.

Original Primary Outcome:

• Gancyclovir initiation [ Time Frame: Day 80 post stem cell transplant ]
• NK (natural killer) immunity in CMV (cytomegalovirus) negative vs CMV positive [ Time Frame: Day 80 post stem cell transplant ]
• Diagnosis of CMV pneumonia [ Time Frame: 1 year ]

Current Secondary Outcome:

• 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.
• 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.

Original Secondary Outcome:

• CMV disease, morbidity, and mortality [ Time Frame: Through 1 year ]
• Efficacy of an individualized strategy for CMV preemptive management on incidence of CMV disease, specifically CMV pneumonia [ Time Frame: By day 80 post transplant ]
• CMV reaction-free survival [ Time Frame: Post-transplant days 21 - 80 ]
• Percent cytotoxicity and ex vivo percent CD56+/CD107B+ cells [ Time Frame: Day 80 post stem cell transplant ]

Dates:
Date Received: September 8, 2010
Date Started: December 2010
Date Completion:
Last Updated: June 3, 2015
Last Verified: June 2015