ARMS - Rapidly Generated Multivirus-Specific CTLs for the Prophylaxis And Treatment of EBV, CMV, Adenovirus, HHV6, and BK Virus (ARMS)
|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: NCT01570283|
Recruitment Status : Completed
First Posted : April 4, 2012
Last Update Posted : December 7, 2017
|First Submitted Date ICMJE||March 27, 2012|
|First Posted Date ICMJE||April 4, 2012|
|Last Update Posted Date||December 7, 2017|
|Start Date ICMJE||September 2012|
|Primary Completion Date||August 2016 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
||Assessment of patients with adverse events after multi-virus specific CTL infusion [ Time Frame: 42 days ]
To determine the safety of escalating doses donor-derived rapidly generated multi-virus-specific cytotoxic T lymphocytes (mCTLs) in patients at risk of developing CMV, adenovirus EBV, HHV6 or BK virus infections after allogeneic stem cell transplant.
|Change History||Complete list of historical versions of study NCT01570283 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
||Assessment of viral load response to the CTL infusion [ Time Frame: 1 year ]
Assess the effect of the CTL infusion on viral load, reconstitution of antiviral immunity post-infusion, and clinical responses
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||ARMS - Rapidly Generated Multivirus-Specific CTLs for the Prophylaxis And Treatment of EBV, CMV, Adenovirus, HHV6, and BK Virus|
|Official Title ICMJE||ARMS - Administration Of Rapidly Generated Multivirus-Specific Cytotoxic T-Lymphocytes For The Prophylaxis And Treatment Of EBV, CMV, Adenovirus, HHV6, And BK Virus Infections Post Allogeneic Stem Cell Transplant|
The subjects eligible for this trial have a type of blood cell cancer, other blood disease or a genetic disease for which they will receive a stem cell transplant. The donor of the stem cells will be either the subject's brother or sister, or another relative, or a closely matched unrelated donor. The Investigators are asking subjects to participate in this study which tests if blood cells from the subject's donor that have been grown in a special way, can prevent or be a effective treatment for early infection by five viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus, BK virus (BKV) and human herpes virus 6 (HHV6).
Adenovirus is a virus that usually causes symptoms of a common cold, but can cause serious life-threatening infections in patients who have weak immune systems. It can affect the lungs and cause very serious pneumonia, and can also damage the gut, liver, pancreas and eyes.
CMV can also cause serious infections in patients with weak or suppressed immune systems. It usually affects the lungs, causing a very serious pneumonia, but it can also affect the gut, 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, but after a transplant, the risk of developing CMV disease is much higher because the immune system is so weak.
EBV is the virus that causes glandular fever or kissing disease. It is also a life long infection like CMV that is normally controlled by immune system. When immunity is weak, the virus can become active and cause fevers, enlarged lymph nodes and sometimes a type of cancer called lymphoma.
BKV is a virus that usually causes symptoms of a common cold such as fever and normally does not cause problems. If the immune system is weakened in some way, for example following a bone marrow transplant, then BKV can cause life-threatening infections affecting mainly the kidneys, bladder, and urinary tract.
HHV6 is another virus that infects most people in childhood causing symptoms like fever, diarrhea and rash. Like CMV, EBV, and BKV, HHV6 remains in the body for life and can cause problems when the immune system is weakened. When this occurs the virus can affect many organs including the brain, lungs, heart, kidney and gastrointestinal tract.
The Investigators want to see if they can use a kind of white blood cell called T lymphocytes (or T cells) to prevent and treat adenovirus, CMV, EBV, BKV and HHV6 in the early stages of reactivation or infection.
The Investigators have grown T cells from the subject's stem cell donor in the laboratory in a way that will train them to recognize the viruses and control them when the T cells are given after a transplant. This treatment with specially trained T cells (also called cytotoxic T cells or "CTLs") has had activity against three of these viruses (CMV, EBV and Adenovirus) in previous studies. In this study the Investigators want to see if they increase the number of viruses that can be targeted to include BKV and HHV6 using a simple and fast approach to make the cells.
To make the CTLs, subject's donors' cells were mixed 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 sufficient numbers of T cells were made, they were tested to make sure they would target the cells infected with these viruses but not the normal cells. Then the cells were frozen.
When the Investigators think the subject needs them, the subject's donor's CTL cells will be thawed and injected into the intravenous line. To prevent an allergic reaction, prior to receiving the CTLs the subject may be given diphenhydramine (Benadryl) and acetaminophen (Tylenol). After the subject receives the cells, Investigators will monitor the levels of these five viruses in the blood. They will also take blood to see how long the T cells they gave the subject are lasting in the body.
If the CTL infusion has helped the subjects infection or if they have had a treatment, for example with steroid drugs that might have destroyed the T cells the subject was given, then they are allowed to receive up to 2 more doses of the cells.
The first part of this study was a dose escalation study. That means that at the beginning, patients were started on the lowest dose (1 of 3 different levels) of T cells. The next group of patients were started at a higher dose. This process continued until all 3 dose levels were studied. They would now like to enroll more patients at the highest dose level to get more information about how the T cells work.
Subjects will continue to be followed by their transplant doctors after the injection. The subject will either be seen in the clinic or they will be contacted by a research nurse to follow up for this study every week for 6 weeks then at 8 week and 3, 6 and 12 months. The subject may have other visits for their standard care. Subjects will also have regular blood tests done to follow their counts and the viral infection. To learn more about the way the T cells are working in the body, up to an extra 30-40 ml (6-8 teaspoons) of blood will be taken before the infusion and then at 1, 2, 4, 5, 6 and 8 weeks and 3 months. Blood should come from the central intravenous line, and should not require extra needle sticks.
If subjects experience a positive response or are taking medicines (such as steroids) that may affect how long T cells stay in the body, they may be able to receive up to two additional doses of the T cells at the same initial dose level from 28 days after their initial dose. After each T-cell infusion, they will be monitored as described above.
Study Duration: Subjects will be on study for approximately one year. If they receive additional doses of the T cells as described above, they will be followed until 1 year after their last dose of T-cells.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Viral Infection|
|Intervention ICMJE||Biological: Multi-virus-specific cytotoxic T lymphocytes
The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level.
Dose Level One: 5x10^6 mCTLs/m2
Dose Level Two: 1x10^7 mCTLs/m2
Dose Level Three: 2x10^7 mCTLs/m2
There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL.
|Study Arms||Experimental: Multi-virus-specific cytotoxic T lymphocytes
Multivirus-specific T cells will be thawed and given by intravenous injection.
Intervention: Biological: Multi-virus-specific cytotoxic T lymphocytes
|Publications *||Papadopoulou A, Gerdemann U, Katari UL, Tzannou I, Liu H, Martinez C, Leung K, Carrum G, Gee AP, Vera JF, Krance RA, Brenner MK, Rooney CM, Heslop HE, Leen AM. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014 Jun 25;6(242):242ra83. doi: 10.1126/scitranslmed.3008825.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||September 2017|
|Primary Completion Date||August 2016 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Patients will be eligible following any type of allogeneic transplant to receive CTLs as prevention or for early reactivations as defined below.
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01570283|
|Other Study ID Numbers ICMJE||H-29966 ARMS|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Study Sponsor ICMJE||ViraCyte|
|Verification Date||January 2017|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP