Giving Epstein-Barr Virus (EBV) Specific Killer T Lymphocytes to Patients Who Have Had Donor Marrow Grafts
| Status: | Recruiting |
|---|---|
| Conditions: | Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 5/5/2014 |
| Start Date: | May 1993 |
| End Date: | May 2016 |
| Contact: | Helen E Heslop, MD |
| Email: | hheslop@bcm.edu |
| Phone: | 832-824-4662 |
Administration of EBV Specific Cytotoxic T Lymphocytes to Recipients of Mismatched-Related or Phenotypically Similar Unrelated Donor Marrow Grafts
Patients have a type of blood cell cancer or other blood problem that is very hard to cure
with standard treatments and s/he will receive a bone marrow transplant. If the patient does
not have a brother or sister whose marrow is a "perfect match", this bone marrow will come
from a donor whose marrow is the best match available. This person may be a close relative
or an unrelated person whose bone marrow best "matches" the patient's, and who agrees to
donate marrow.
In normal people, the Epstein-Barr (EB) virus infection causes a flu like illness and
usually gets better when the immune system controls the infection. The virus, however,
remains hidden in the body for life. After a transplant, while the new immune system is
growing back, the EB virus can come out and infect cells and cause them to grow in an
uncontrolled manner. Patients can develop fevers, swollen lymph nodes and damage to other
organs such as kidneys and lungs. This infection acts like a cancer because the cells
infected with EB virus grow very quickly and there is no known effective treatment. This
sort of infection will occur in between 10-30% of patients receiving a transplant from a
donor who is not a perfect match, and has been fatal in nearly all these cases.
This infection occurs because the immune system cannot control the growth of the cells. We
want to see if we can prevent it from happening or treat it by giving the patient a kind of
white blood cell called T cells that we have grown from the marrow donor. These cells have
been trained to attack EB virus infected cells. We will grow these T cells from blood taken
from the donor at the time of bone marrow harvest. These T cells will be stimulated with the
donor's EB virus-infected cells which have been treated with radiation so they cannot grow.
After mixing these cells together we will be able to grow special T cells from the donor
that can attack EB virus infected cells. We will then collect the T cells and make sure they
can kill the virus infected cells. These EBV specific T cells are an investigational product
not approved by the Food and Drug Administration.
with standard treatments and s/he will receive a bone marrow transplant. If the patient does
not have a brother or sister whose marrow is a "perfect match", this bone marrow will come
from a donor whose marrow is the best match available. This person may be a close relative
or an unrelated person whose bone marrow best "matches" the patient's, and who agrees to
donate marrow.
In normal people, the Epstein-Barr (EB) virus infection causes a flu like illness and
usually gets better when the immune system controls the infection. The virus, however,
remains hidden in the body for life. After a transplant, while the new immune system is
growing back, the EB virus can come out and infect cells and cause them to grow in an
uncontrolled manner. Patients can develop fevers, swollen lymph nodes and damage to other
organs such as kidneys and lungs. This infection acts like a cancer because the cells
infected with EB virus grow very quickly and there is no known effective treatment. This
sort of infection will occur in between 10-30% of patients receiving a transplant from a
donor who is not a perfect match, and has been fatal in nearly all these cases.
This infection occurs because the immune system cannot control the growth of the cells. We
want to see if we can prevent it from happening or treat it by giving the patient a kind of
white blood cell called T cells that we have grown from the marrow donor. These cells have
been trained to attack EB virus infected cells. We will grow these T cells from blood taken
from the donor at the time of bone marrow harvest. These T cells will be stimulated with the
donor's EB virus-infected cells which have been treated with radiation so they cannot grow.
After mixing these cells together we will be able to grow special T cells from the donor
that can attack EB virus infected cells. We will then collect the T cells and make sure they
can kill the virus infected cells. These EBV specific T cells are an investigational product
not approved by the Food and Drug Administration.
We will obtain blood from the donor and will first make a B cell line called a
lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV
called B95. We will then use this EBV-infected cell line (which have been treated with
radiation so that they cannot grow) as stimulator cells and mix it with more blood. This
stimulation will train the T cells to kill EBV infected cells and result in the growth of an
EBV specific T cell line. We will then test the T cells to make sure that they kill the EBV
infected cells and not the normal cells and freeze them.
The marrow donor's T cells will be thawed and injected through an intravenous line for a
period of 10 minutes. The subject may be premedicated with diphenhydramine (Benadryl) and
acetaminophen (Tylenol). We would give one dose of the cells on or after day 45 following
transplant if the subject agreed and was well enough. If the EBV DNA levels remain high or
the subject has persistent disease, s/he may be eligible to receive up to 5 additional
injections of T cells at the original dose at monthly intervals. After the subject has
received the T cells, s/he will be contacted by the research nurse or another member of the
study team weekly for 6 weeks, then once every three months for a year so that we can check
on his/her progress.
We will continue to follow the subject in the BMT clinic after the injections. To learn more
about the way the T cells are working, an extra 40 mls (about 8 teaspoonfuls) of blood will
be taken pre-infusion, 4 hours after the infusion, 3-4 days post infusion (optional) and at
1, 2, 4 and 6 weeks after the T cell infusions, and then at 3, 6, 9, and 12 months post
infusion. The blood should come from the central intravenous line, and should not require
extra needle sticks.
lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV
called B95. We will then use this EBV-infected cell line (which have been treated with
radiation so that they cannot grow) as stimulator cells and mix it with more blood. This
stimulation will train the T cells to kill EBV infected cells and result in the growth of an
EBV specific T cell line. We will then test the T cells to make sure that they kill the EBV
infected cells and not the normal cells and freeze them.
The marrow donor's T cells will be thawed and injected through an intravenous line for a
period of 10 minutes. The subject may be premedicated with diphenhydramine (Benadryl) and
acetaminophen (Tylenol). We would give one dose of the cells on or after day 45 following
transplant if the subject agreed and was well enough. If the EBV DNA levels remain high or
the subject has persistent disease, s/he may be eligible to receive up to 5 additional
injections of T cells at the original dose at monthly intervals. After the subject has
received the T cells, s/he will be contacted by the research nurse or another member of the
study team weekly for 6 weeks, then once every three months for a year so that we can check
on his/her progress.
We will continue to follow the subject in the BMT clinic after the injections. To learn more
about the way the T cells are working, an extra 40 mls (about 8 teaspoonfuls) of blood will
be taken pre-infusion, 4 hours after the infusion, 3-4 days post infusion (optional) and at
1, 2, 4 and 6 weeks after the T cell infusions, and then at 3, 6, 9, and 12 months post
infusion. The blood should come from the central intravenous line, and should not require
extra needle sticks.
INCLUSION CRITERIA:
- All patients receiving a T cell depleted BMT from a mismatched family member or
unrelated donor will be eligible for this protocol. In addition, patients receiving a
matched sibling transplant or T replete transplant may be eligible if they are at
high risk of developing EBV LPD because of their underlying disease (e.g
Wiskott-Aldrich or Ataxia Telangiectasia) or have a past history of EBVLPD or other
EBV associated malignancy.
- O2 saturation > 90% on room air
EXCLUSION CRITERIA:
- Exclusion criteria for BMT will be as detailed in the relevant protocol.
Exclusion criteria at time of administration CTLs:
- Patients with GVHD of Grade II or greater.
- Patients with severe renal disease (i.e., creatinine clearance less than half normal
for age).
- Patients with severe hepatic disease (bilirubin greater than twice normal, or SGOT
greater than 3 x normal).
- Patients with a severe intercurrent infection.
- Patients with a life expectancy <6 weeks
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