Modified Preemptive CMV Management Strategy After Allogeneic Hematopoietic Cell Transplantation and Laboratory Correlation With Innate Immune Function
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 153
- 试验地点
- 1
- 主要终点
- Initiation of anti-CMV therapy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: infection prophylaxis and management (Procedure)
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.
干预措施: laboratory biomarker analysis (Other)
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.
干预措施: flow cytometry (Other)
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.
干预措施: DNA analysis (Genetic)
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.
干预措施: RNA analysis (Genetic)
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.
干预措施: management of therapy complications (Procedure)
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.
干预措施: ganciclovir (Drug)
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.
干预措施: valganciclovir (Drug)
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.
干预措施: foscarnet sodium (Drug)
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.
干预措施: antiviral therapy (Procedure)
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.
干预措施: polymerase chain reaction (Genetic)
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.
干预措施: protein expression analysis (Genetic)
结局指标
主要结局
Initiation of anti-CMV therapy
时间窗: 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
时间窗: 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.
次要结局
- Percent cytotoxicity and ex vivo percent CD56+/CD107B+ cells(Day 120 post stem cell transplant)
- CMV reactivation-free survival, monitored using a real time PCR assay for CMV DNA in plasma(Up to day 100 post-transplant)