Allogeneic Virus-Specific Cytotoxic T-Lymphocytes(CTL), Persistent/Recurrent Viral Infection Post-HSCT (EAP CHALLAH) (EAP CHALLAH)
|ClinicalTrials.gov Identifier: NCT01945619|
Expanded Access Status : No longer available
First Posted : September 18, 2013
Last Update Posted : January 21, 2016
Subjects have a type of blood cell cancer, other blood disease or a genetic disease for which they received a stem cell transplant. After transplant while the immune system grows back the subjects have an infection with one or more of three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) or adenovirus - that has persisted or come back despite standard therapy.
Adenovirus is a virus that causes symptoms of a common cold normally but can cause serious life-threatening infections in patients who have weak immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the gut, the liver, the pancreas and the eyes.
CMV is a virus that can also cause serious infections in patients with suppressed immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the intestinal tract, the liver and the eyes. Approximately 2/3 of normal people harbor this virus in their body. In healthy people CMV rarely causes any problems because the immune system can keep it under control. If the subject and/or the subject's donor are positive for CMV, s/he is at risk of developing CMV disease while his/her immune system is weak post transplant.
EBV is the virus that causes glandular fever or kissing disease. It is also normally controlled by a healthy immune system, but when the immune system is weak, it can cause fevers, enlarged lymph nodes and sometimes develop into a type of cancer called lymphoma.
This treatment with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from the transplant donor. However, as it takes 2-3 months to make the cells, that approach is not practical when the subject already has an infection. We want to find out if we can use CTLs which have already been made from another donor that match the subject and his/her donor as closely as possible and if the CTLs will last in the body and have activity against these viruses.
In a recent study these cells were given to 50 patients with viral infections post transplant and over 70% had a complete or partial response. The purpose of this study is to make CTL lines leftover from that previous study available to patients with viral infections that have not responded to standard treatments.
These virus-specific CTLs are an investigational product not approved by the FDA.
|Condition or disease||Intervention/treatment|
|EBV Infection CMV Infection Adenoviral Infection||Biological: Trivirus-Specific CTLs|
The CTL lines were made at Baylor College of Medicine from donors for other transplant patients or other normal donors from the National Marrow Donor Program. All donors were screened in the same way as blood donors. When the CTL lines were made, blood was taken from the donors and used to grow T cells. To do this, we first infected a type of blood cells called monocytes with a specially produced adenovirus gene that also carries part of the CMV gene. The monocytes with these new genes then stimulated the T cells. This stimulation trained the T cells to kill cells with this part of the CMV virus or with adenovirus.
We then grew these CTLs with more stimulation with EBV infected cells (which we made from donor blood by infecting them with EBV in the laboratory). We also put the adenovirus that carries the CMV gene into these EBV infected cells so that they too had CMV and adenovirus proteins. These EBV infected cells were treated with radiation so they cannot grow. By this type of culture, we grew out T cells that can see and attack cells infected with EBV, adenovirus or CMV. Once we made sufficient numbers of T cells we tested them to make sure they killed cells infected with these viruses and then froze them.
The cells will be thawed and injected into an intravenous line over 1-5 minutes.
All participants on this study will get the same dose of cells. However if the subject's infection responds to the CTLs, s/he may be offered up to 4 more doses at two-week intervals. If the infection does not respond, the doctors may also try a line from a different donor.
|Study Type :||Expanded Access|
|Official Title:||Expanded Access Protocol: Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation or Infection With Adenovirus, CMV and EBV After HSCT|
- Biological: Trivirus-Specific CTLs
Patients will receive up to 2 x 10^7 CHM-CTL/m2 as a single infusion and may receive up to 4 additional infusions at intervals of at least 2 weeks.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01945619
|United States, Texas|
|Houston Methodist Hospital|
|Houston, Texas, United States, 77030|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Helen E Heslop, MD||Baylor College of Medicine|