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
To make the CTLs we mixed the subjects donors' 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 we made sufficient numbers of T
cells, we tested them to make sure they would target the cells infected with these viruses
but not the normal cells. Then we froze the cells.
When we 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 we will monitor the levels of these five viruses in the
blood. We will also take blood to see how long the T cells we 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.
This is a dose escalation study. This means that at the beginning, patients will be started
on the lowest dose (1 of 3 different levels, 2-4 patients at each dose level) of T cells and
followed for 42 days for dose limited toxicity evaluations. The decision whether it is safe
to escalate to next dose level or not will be made after at least two patients have finished
their 42 days. Once that dose schedule proves safe, the next group of patients will be
started at a higher dose. This process will continue until all 3 dose levels are studied. If
the side effects are too severe, the dose will be lowered or the T cell injections will be
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Patients with acute GvHD grades III-IV within 42 days of the last dose of CTLsinfusion
To determine the feasibility and safety of escalating doses of 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.
Helen Heslop, MD
Baylor College of Medicine
United States: Institutional Review Board
|Texas Children's Hospital||Houston, Texas|
|The Methodist Hospital||Houston, Texas 77030|