A Phase 1b Safety and Immunogenicity Study of Cytomegalovirus (CMV) Directed Type 1 Polarized Dendritic Cell Vaccination (αDC1) After Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Number of CMV pp56 reactive T cells
研究概览
简要总结
This phase Ib trial evaluates the safety and most effective dose of a cytomegalovirus (CMV) pp65 peptide-loaded alpha-type-1 polarized dendritic cell (CMV-alphaDC1) vaccination in patients who are undergoing an allogeneic hematopoietic stem cell transplant. CMV is an opportunistic infection that can occur or reactivate after allogeneic hematopoietic stem cell transplant as a result of immunosuppression. The CMV-alphaDC1 vaccine is made of white blood cells that have been exposed to molecules called cytokines, as well as CMV proteins. Introducing these dendritic cells to the patients immune system may activate an immune response to CMV, protecting against infection or reactivation.
详细描述
PRIMARY OBJECTIVES:
I. Determine the safety of cytomegalovirus (CMV) pp65 peptide loaded alpha-type 1 polarized dendritic cell (CMV-alphaDC1) vaccination after allogeneic hematopoietic cell transplantation (alloHCT).
II. Determine the immunogenicity of CMV-alphaDC1 vaccination after alloHCT.
SECONDARY OBJECTIVES:
I. Evaluate the effect of CMV-alphaDC1 vaccination after alloHCT on late CMV reactivation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Recipient age >= 18 years of age
- •The recipient is CMV seropositive
- •The recipient is planned to receive an allogeneic peripheral blood stem cell graft
- •The recipient is planned to receive fludarabine, melphalan, and total body irradiation for the transplant conditioning regimen
- •The recipient is planned to receive micro-dose methotrexate, tacrolimus, and mycophenolate mofetil for acute graft versus host disease (GvHD) prophylaxis
- •The recipient has an expected hematopoietic cell transplantation-comorbidity index (HCT-CI) score of 4 or less based upon the data available at the time of eligibility assessment
- •The recipient must understand the investigational nature of this study and has signed an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedures
- •The donor is CMV seronegative or seropositive
- •The donor is 8/8 human leukocyte antigen (HLA) (DR-B1, A, B, C) matched to the recipient
- •The donor is willing and able to donate peripheral blood mononuclear cells in addition to peripheral blood stem cells
- •The donor is willing to sign informed consent
排除标准
- •The recipient is CMV seronegative
- •The recipient is planned to receive T cell depletion in vivo (anti-thymocyte globulin [ATG], alemtuzumab, post-transplant cyclophosphamide) or ex vivo (alpha-beta T cell depleted or CD34+ selected grafts) as acute GvHD prophylaxis
- •The graft source is cord blood or bone marrow
- •The donor or recipient has HLA DRB1*0301 or DRB1*1501 alleles
- •The recipient has a very high disease risk index (DRI) based upon the data available at the time of eligibility assessment
- •The recipient has a medical, behavioral, or social condition which in the opinion of the investigators would preclude compliance with the study
结局指标
主要结局
Number of CMV pp56 reactive T cells
时间窗: At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
The number of CMV pp65 reactive T cells will be determined by cytokine secretion (such as IFN-gamma) with ELISPOT before and after vaccination with CMV-alphaDC1. Assessed by the change in the number of CMV specific T cells before and after treatment, which is compared using a one-sided paired t-test. The number of CMV specific T cells will be summarized before and after treatment using the appropriate descriptive statistics, with the mean change estimated using a 90% confidence interval.
Incidence of dose limiting toxicities
时间窗: Up to 2 years
For each dose level of cytomegalovirus (CMV) pp65 peptide loaded alpha-type 1 polarized dendritic cell (CMV-alphaDC1) vaccination that is tested. Will be summarized by dose level using frequencies and relative frequencies.
Number of multifunctional CMV antigen specific T cells
时间窗: At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
The number of multifunctional CMV antigen specific T cells will be determined by flow cytometry before and after vaccination with CMV-alphaDC1. Assessed by the change in the number of CMV specific T cells before and after treatment, which is compared using a one-sided paired t-test. The number of CMV specific T cells will be summarized before and after treatment using the appropriate descriptive statistics, with the mean change estimated using a 90% confidence interval.
次要结局
- Incidence of late CMV reactivation after allogeneic hematopoietic stem cell transplant(From day 85 to 365)
- Incidence of non-relapse mortality after allogeneic hematopoietic stem cell transplant(Up to 2 years)