Clinical Trial: Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL)
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation Or Infection With Adenovirus, CMV and EBV After Hemopoiet
Brief Summary:
This trial is designed to evaluate the feasibility, safety and efficacy of most closely HLA-matched multivirus specific CTL lines (CHM-CTLs) in HSCT patients with EBV, CMV or adenovirus infections that are persistent despite standard therapy.
The primary objective of the study is to assess safety and feasibility of administering CTLs. Survival data will be collected by asking the transplant center to submit the routine Transplant Essential Data form that is sent to the Stem Cell Transplant Outcomes Database at 100 days and 1 year and includes data on survival status and other outcome measures.
Detailed Summary:
Patients may be screened for study entry when they have persistent disease despite standard therapy as defined in the inclusion criteria. At that stage a search will be done of the available lines. Lines were generated from HSCT donors who consented to the use of CTLs not required for their recipient for research or from normal donors. All donors were screened and deemed to be eligible as transplant donors. We will also manufacture additional lines with the goal of covering common HLA types and will consult with the NMDP to determine what HLA types would be desirable. Additional donors will be screened by a transplant donor center physician and must be deemed eligible before a line can be manufactured.
CTL Lines: We will use trivirus specific CTL lines generated as described previously. Generation of trivirus-specific CTL lines requires the generation of several different components from PBMC. The CTL line will be derived from donor peripheral blood T cells, by multiple stimulations with antigen-presenting cells (APCs) presenting CMV, EBV and adenovirus antigens and expansion with interleukin-2 (IL-2). The APCs used to stimulate and expand the CMV-specific T cells will be derived from patient mononuclear cells and B lymphocytes.
To initiate the trivirus-specific CTL line, PBMC will be transduced with an adenovirus vector (Ad5f35-pp65) expressing the immunodominant antigen of CMV, pp65. The monocyte fraction of PBMC expressed and presented CMV-pp65 peptide epitopes to the CMV-specific T cell fraction of the PBMC, while the virion proteins from the adenovirus vector were processed and presented to the adenovirus-specific T cell fraction.
To expand trivirus -specific T cells we used EBV-transformed B lymphoblastoid cell lines (EBV-LCLs) transduced with Ad5f35-pp65. This transd
Sponsor: Baylor College of Medicine
Current Primary Outcome: The primary purpose of the study is to assess the safety of administering CHM-CTLs in transplant patients with EBV, CMV, or adenovirus infection. We have elected to use a dose of 2 x 10^7 CHM-CTLs/m2. [ Time Frame: 1 year ]
Original Primary Outcome: The primary purpose of the study is to assess the safety of administering CHM-CTLs in transplant patients with EBV, CMV, or adenovirus infection. We have elected to use a dose of 2 x 107 CHM-CTLs/m2. [ Time Frame: 1 year ]
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Baylor College of Medicine
Dates:
Date Received: June 20, 2008
Date Started: November 2008
Date Completion:
Last Updated: March 25, 2016
Last Verified: March 2016
