Administration of Virus-Specific Cytotoxic T-Lymphocytes (LYPTAIST)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00590083|
Recruitment Status : Completed
First Posted : January 10, 2008
Last Update Posted : February 19, 2014
|Condition or disease||Intervention/treatment||Phase|
|Adenovirus Infection||Biological: CTL administration||Phase 1|
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, reconstitution of the host with in vitro expanded CTLs is an effective approach to prevent and treat these diseases. Adoptive immunotherapy with in vitro expanded CTLs has proved effective in preventing and treating diseases related to Epstein Barr virus (EBV) infections 5; 6 and cytomegalovirus (CMV) reactivations7 in hematopoietic stem cell transplant (HSCT) recipients. A promising strategy to generate donor-derived Ad-specific CTL is the infection of monocytes that direct the CTL response to viral capsid antigens8. This approach allows exposure to all proteins in the Ad protein coat, leading to presentation of multiple, undefined antigen epitopes. Hence, the investigators now plan to use a recombinant Ad vector for infection of donor-derived monocytes. These infected monocytes will then be used as antigen presenting cells (APC) to generate Ad-specific CTL in vitro. For the expansion of the Ad-specific CTL, the second stimulation will use irradiated, Ad-infected monocytes and subsequent stimulations will use donor-derived Lymphoblastoid Cell Lines (LCL) transduced with the Ad vector as an APC 9.
The investigators propose to evaluate this approach for the prophylaxis of Ad reactivation and disease in the recipients of matched unrelated donor or mismatched family member bone marrow allografts, who are at high risk for this complication. Initially, the investigators will give the donor-derived Ad-specific CTLs to patients in a dose escalation study to determine their safety and immunologic and virologic efficacy.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Administration of Virus-Specific Cytotoxic T-Lymphocytes for the Prophylaxis and Therapy of Adenovirus Infection Post Allogeneic Stem Cell Transplant|
|Study Start Date :||July 2003|
|Actual Primary Completion Date :||January 2011|
|Actual Study Completion Date :||January 2011|
Experimental: Virus Specific Cytoxic T lymphocytes
Virus Specific Cytoxic T lymphocytes
Biological: CTL administration
Adenovirus specific T cells will be given by intravenous injection from day 30 post transplant.
One infusion of Adenovirus-specific CTL given to patients at risk for Adenoviral disease after matched or mismatched unrelated or matched or mismatched related donor stem cell transplant. Four dose levels will be explored. The lowest level will be 1x dose of 5x10e6cells/m2 and the highest will be 1x dose of 1.35x10e8/m2.
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00590083
|United States, District of Columbia|
|National Institute of Health (NIH)|
|Washington, District of Columbia, United States, 20894|
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|The Methodist Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Catherine Bollard, MD||Baylor College of Medicine|