Multivirus-specific T Cells for the Treatment of Virus Infections After Stem Cell Transplant (CHARMS)
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|ClinicalTrials.gov Identifier: NCT02108522|
Recruitment Status : Active, not recruiting
First Posted : April 9, 2014
Last Update Posted : May 29, 2019
Patients enrolled on this study will have received a stem cell transplant. After a transplant, while the immune system grows back the patient is at risk for infection. Some viruses can stay in the body for life and if the immune system is weakened, like after a transplant, they can cause life threatening infections.
Patients enrolled on this study will have had an infection with one or more of the following viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV), BK virus, JC virus, adenovirus or HHV6 (Human Herpes Virus 6).
Investigators want to see if they can use a kind of white blood cell called T cells to treat infections of these viruses after a transplant. Investigators have observed in other studies that treatment with specially trained T cells has been successful when the cells are made from the transplant donor. However as it takes 1-2 months to make the cells, that approach is not practical when a patient already has an infection.
Investigators have now generated multivirus-specific T cells (VSTs) from the blood of healthy donors and created a bank of these cells. Investigators have previously successfully used frozen multivirus-specific T cells from healthy donors to treat virus infections after bone marrow transplant and now have improved the production method to make it safer and target more viruses.
In this study, investigators want to find out if they can use these banked VSTs to fight infections caused by the viruses mentioned above.
|Condition or disease||Intervention/treatment||Phase|
|Infection||Biological: Multivirus Specific T cells||Not Applicable|
These VST lines have been made at Baylor College of Medicine from donors for other transplant patients or other normal donors some of whom were from the National Marrow Donor Program. All donors have been screened with the standard blood bank donor questionnaire, medical history and testing for infectious disease by a doctor who is experienced in screening transplant donors. Only donors who have cleared this process and were deemed to be eligible provided blood for VST generation.
The lines were made using a special process. To make the VSTs investigators mixed donor cells with small pieces of proteins, called peptides that come from adenovirus, CMV, EBV, BKV and HHV6. These peptides stimulate donor T cells that react against the viruses to grow and train the donor T cells to kill cells that are infected with CMV, EBV, adenovirus, BKV and HHV6.
Once the investigators made sufficient numbers of VSTs, they tested them to make sure they would target cells infected with these virusesbut not normal cells. Then the cells were frozen.
For patients treated on this study, the VSTs will be thawed and injected into their intravenous line. The patient will remain in the clinic for at least one hour after the infusion. After the patient receives the cells, their transplant doctor will monitor the levels of the virus the patient is infected with in their blood. The investigators will also take blood to see how long the VSTs given to the patient last in their body.
The patient will continue to be followed by their doctors after the injection. The patient will either be seen in the clinic or will be contacted by a research nurse to follow up for this study every week for 6 weeks then at 3, 6 and 12 months. The patient may have other visits for their standard care.
The patient will also have regular blood tests done to follow their counts and the viral infection, but most of these will be done as part of their standard medical care. To learn more about the way the VSTs are working in the patient's body, up to an extra 30-40 ml (6-8 teaspoons) of blood will be taken before the infusion and then at 1, 2, 3, 4, 6 weeks and 3 months. Blood should come from the central intravenous line, and should not require extra needle sticks.
All participants on this study will be infused with the same number (dose) of cells. If after the first treatment the patient has a persistent infection, we would discuss this with him/her and allow an option to receive more treatments. These additional treatments might be with cells from the same donor or if we feel that there is another donor's whose cells might be better for the patient, we would use cells from a different donor. This second product will be administered at the same dose level 28 days after the initial infusion, and subsequent infusions should be at least 14 days apart. After each VST infusion, the patient will be monitored as described above.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||59 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Administration of Most Closely HLA-matched Multivirus-specific Cytotoxic T-Lymphocytes for the Treatment of EBV, CMV, Adenovirus, HHV6, and BK Virus Infections Post Allogeneic Stem Cell Transplant|
|Study Start Date :||June 2014|
|Actual Primary Completion Date :||January 2018|
|Estimated Study Completion Date :||June 2020|
Experimental: Multivirus Specific T cells
Partially HLA-matched multivirus specific T cells (VSTs) will be thawed and given by intravenous injection. Patients will receive 2 x 10^7 VSTs/m2 as a single infusion. In the rare case where insufficient banked cell product is available, a lower number of cells may be infused after discussion with the principal investigator, patient and/or guardian and the treatment team.
If after the first treatment there is persistent infection, there is an option to receive more treatments. These additional treatments might be with cells from the same donor or another donor whose cells are also felt to be a good match for the patient and effective against their virus. This second product will be administered at the same dose level 28 days after the initial infusion, and subsequent infusions should be at least 14 days apart.
Biological: Multivirus Specific T cells
- Number of patients where a suitable VST line could be found [ Time Frame: within 24 hours of receiving recipient HLA information ]Consented subjects will be screened for a suitable VST line to asses feasibility of finding a sufficiently matching VST line.
- Number of patients with acute GvHD grades III-IV [ Time Frame: 42 days ]Safety of VSTs based on patients with acute GvHD grades III-IV within 42 days of the last dose of VSTs
- Number of patients with grades 3-5 non-hematologic adverse events related to the T cell product [ Time Frame: 28 days ]Safety of VSTs based on patients with grades 3-5 non-hematologic adverse events that are at least possibly related to the T cell product within 28 days of the last VST dose by NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.X.
- Viral load at 6 weeks [ Time Frame: 6 weeks ]Effects of partially HLA-matched VSTs on viral loads
- Number of patients with reconstitution of antiviral immunity [ Time Frame: 12 months ]Reconstitution of Antiviral Immunity is defined as virus-specific T cells > 10 SFC/5x10e5 PBMCs for one virus or additive within the first 6 weeks
- Persistence of VSTs [ Time Frame: 6 weeks ]Number of patients with circulating T cells of confirmed 3rd party origin as measured by epitope mapping and other techniques
- Association between HLA matching and viral load reduction [ Time Frame: 6 weeks ]Viral reduction between patients treated with low HLA match and high HLA match lines will be compared
- Number of patients with an antiviral responses 42 days after the first dose of VSTs [ Time Frame: 42 days ]Antiviral response rate is defined as the proportion of subjects with a positive response is defined as the viral load by at least 50% (partial response), or return to the normal level (complete response) for the treated virus
- Number of patients with viral reactivations within 12 months [ Time Frame: 12 months ]All CMV, EBV, adenovirus, BK virus, JC virus and HHV6 infections/reactivations, other than the primary infection, occurring within 12 months of VST infusion
- Number of patients with secondary graft failure at 30 days [ Time Frame: 30 days ]Secondary graft failure is defined as initial neutrophil engraftment followed by subsequent decline in the ANC to less than 500/mm^3 for three consecutive measurements on different days, unresponsive to growth factor therapy that persists for at least 14 days in the absence of a known cause such as relapse
- Number of patients with chronic GVHD [ Time Frame: 12 months ]Number of patients with new or worsened chronic GVHD by standard criteria
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): NCT02108522
|United States, Texas|
|Houston Methodist Hospital|
|Houston, Texas, United States, 77030|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Bilal Omer, MD||Baylor College of Medicine|