Clinical Trial: Administration of Virus-Specific Cytotoxic T-Lymphocytes
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Administration of Virus-Specific Cytotoxic T-Lymphocytes for the Prophylaxis and Therapy of Adenovirus Infection Post Allogeneic Stem Cell Transplant
Brief Summary: The main purpose of this study is to see if these T-lymphocytes are safe. To make these Ad-specific T lymphocytes the investigators will obtain blood from the stem cell donor and transfer Ad into another type of blood cell, called monocytes. These cells can then stimulate the T lymphocytes and train them to kill cells infected with Ad. The investigators will then grow these Ad-specific T lymphocytes by more stimulation with Ad-infected monocytes and a third type of blood cell called a B lymphoblast from the donor. After testing the T -lymphocytes, the investigators will inject them into patients after transplant who are at high risk of serious Ad virus infection. The investigators will make sure the injected cells are safe and see if they affect the growth and behavior of adenoviruses in the patient's own body.
Detailed Summary:
Viral infection is one of the major causes of morbidity and mortality in patients who receive bone marrow transplantation (BMT) from unrelated or mismatched donors. This increased risk of infection relates to a number of factors including the immunosuppressive regimens these patients receive, delayed immune recovery and the greater genetic disparity between donor and recipient that result in defective interactions between antigen presenting cells and immune system effector cells. In most cases viral infection post BMT results from reactivation of latent virus and CMV, EBV and adenoviruses (Ad) are the commonest viral pathogens causing disease after transplant.
The incidence of Ad infection is >25% for patients at risk in the first 100 days after transplant 1 2. In the transplant population, adenovirus is recoverable from many sites and may cause hemorrhagic cystitis, pneumonitis, nephritis, hepatitis, colitis and pancreatitis, often with severe morbidity and a mortality approaching 60%3. The most frequently used drug for the treatment of adenoviral infections is Cidofovir. But while there are occasional reports of responses to Cidofovir, no approved antiviral agent has proven efficacy for the treatment of severe Ad disease, nor are there any prospective randomized, controlled trials of potentially useful anti-Ad therapies 4. With the increasing use of so-called submyeloablative or reduced intensity, highly immunosuppressive conditioning regimens, higher rates of Ad infections/reactivation have been observed due to prolonged immune suppression. The onset of Ad disease/reactivation has recently been reported to occur at a median of 18 days post-transplant (range -7/>+100) 2.
As viral complications in these patients are clearly associated with the lack of recovery of virus-specific cellular immune responses, reconstitut
Sponsor: Baylor College of Medicine
Current Primary Outcome:
- safety, toxicity and MTD of 1 IV injection of donor-derived adenovirus-specific CTLs given as adenovirus prophylaxis to patients at risk of developing adenovirus infection after allogeneic stem cell transplant. [ Time Frame: 1 year ]
- To evaluate the recovery of virus-specific immunity after CTL infusion and assess its correlation with protection from viral load and disease. [ Time Frame: 1 year ]
- To obtain preliminary information regarding whether the presence of antigen is required for Ad-specific CTL persistence in vivo. [ Time Frame: 1 year ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Baylor College of Medicine
Dates:
Date Received: December 21, 2007
Date Started: July 2003
Date Completion:
Last Updated: February 14, 2014
Last Verified: February 2014
