Nivolumab With Epstein Barr Virus Specific T Cells (EBVSTS), Relapsed/Refractory EBV Positive Lymphoma (PREVALE)



Status:Recruiting
Conditions:Lymphoma, Lymphoma, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:Any
Updated:1/24/2018
Start Date:February 16, 2016
End Date:February 16, 2020
Contact:Ravi Pingali, MD
Email:spingali@houstonmethodist.org
Phone:713-441-6220

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Phase I Study Combining Nivolumab With Epstein Barr Virus Specific T Cells (EBVSTS) in Relapsed/Refractory EBV Positive Lymphoma Patients (PREVALE)

Subjects have a type of a lymph node cancer called Non-Hodgkin's Lymphoma (NHL) or
lymphoproliferative disease (LPD), which affects their immunity, blood production, and can
involve multiple other organs in the body. Their disease has come back or has not gone away
after treatment. The experimental treatment plan consists of an antibody therapy called
"Nivolumab" that helps the subjects' T-cells control the tumor, and special immune system
cells called EBV-specific cytotoxic T lymphocytes, also a new therapy whose side effects are
well studied.

Some patients with NHL or LPD are infected with the virus that causes infectious
mononucleosis (called Epstein-Barr virus, or EBV) before or at the time of their diagnosis.
The cancer cells that are infected by EBV are able to hide from the body's immune system and
escape destruction. Investigators want to see if special white blood cells, called T cells,
that have been trained to kill cells infected by EBV can survive in the blood and affect the
tumor.

Investigators have used this sort of therapy to treat a different type of cancer that occurs
after bone marrow or solid organ transplant called post-transplant lymphoma with good
success. These cells are called EBV-specific cytotoxic T-lymphocytes (EBVSTs), and are
effective in treating these diseases. These EBVSTs are experimental and not yet approved by
the Food and Drug Administration (FDA).

Sometimes it is not possible to grow these cells; or they may not last very long in the body
after being given into the vein thereby having only limited time to fight the tumor. With
this study, investigators aim to increase the duration of time that the T cells can last in
the body and can effectively fight the cancer by using nivolumab. Nivolumab is FDA approved
for treatment of other kinds of cancer like lung cancer and a skin cancer called Melanoma.

The purpose of this study is to find out if EBVST cells in combination with nivolumab are
safe, to learn what the side effects are, and to see whether this therapy may help patients
with EBV related lymphoma or LPD.

The investigators will draw blood from the subject to make EBV-specific cytotoxic
T-lymphocytes (EBVSTs) in the lab. Investigators will make the cells by first growing a
special type of cells called dendritic cells (DCs) or monocytes to stimulate the T cells.
Then they will add specially produced mixtures of proteins that included the LMP, EBNA1, and
BARF proteins. These are used to stimulate T cells. As the T cells grow, investigators add
some of the subject's cells expressing these proteins to stimulate them. They also add a cell
called K562 that has had new genes put inside it so it expresses proteins that stimulate the
immune system to encourage the T cells to grow. This stimulation trains the EBVSTs to kill
cells with EBV proteins on their surface. These cells will be grown and frozen.

The cells grown in the lab will be thawed and injected into the subject's vein over 2-10
minutes. Initially, one dose of the drug nivolumab is given one day before the EBVST cells
are infused (on day 0) and then every 2 weeks for a total of four doses of nivolumab.
Subjects will receive two infusions of the EBVST cells. The first infusion will be given on
Day 1 and a second infusion of T cells on Day 15.

If eligible, subjects may receive up to three additional doses of the T cells 6-12 weeks
apart and each additional T cell infusion would be preceded by one dose of nivolumab a day
prior.

Subjects will have medical and blood tests at predetermined time points. Investigators will
follow subjects closely after treatment for any side effects for at least for 1 year after
the subject's last infusion.

Inclusion Criteria:

PROCUREMENT Inclusion

- Any patient, regardless of age* or sex, with measurable EBV-positive Hodgkin's or
non-Hodgkin's Lymphoma, (regardless of the histological subtype)^ or EBV (associated)-
T/NK- or B cell lymphoproliferative disease

* The first 3 patients enrolled will be adults. Patients <18 years of age are eligible
if those first 3 patients do not experience dose limiting toxicity considered to be
primarily related to the EBVST or Nivolumab.

^ Patients with relapsed or refractory lymphoma who failed or are ineligible for an
autologous hematopoietic cell transplantation are also eligible for this study.

- EBV positive tumor (can be pending)

- Weighs at least 12kg

- Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given a copy of informed consent.

- Life expectancy of greater than 6 weeks.

TREATMENT Inclusion

- Any patient, regardless of age* or sex, with measurable EBV-positive Hodgkin's or
non-Hodgkin's Lymphoma, (regardless of the histological subtype)^ or EBV (associated)-T/NK-
or B cell lymphoproliferative disease

* The first 3 patients enrolled will be adults. Patients <18 years of age are eligible if
those first 3 patients do not experience dose limiting toxicity considered to be primarily
related to the EBVST or Nivolumab.

^ Patients with relapsed or refractory lymphoma who failed or are ineligible for an
autologous hematopoietic cell transplantation are also eligible for this study.

And

- Hodgkin's lymphoma patients in second relapse or first relapse and refractory to at
least two lines of salvage chemotherapy including Brentuximab Vedotin or primary
refractory disease after at least two lines therapy or

- Non- Hodgkin's lymphoma patients in first relapse and/or refractory to at least one
salvage chemotherapy or with primary refractory disease after at least two lines of
therapy or in second or subsequent relapse or

- T/NK- or B lymphoproliferative disease in first relapse and/or refractory to at least
one salvage chemotherapy or with primary refractory disease after at least two lines
of therapy or in second or subsequent relapse

- EBV positive tumor

- Patients with life expectancy >/= 6 weeks.

- Patients with bilirubin less than or equal to 3x upper limit of normal

- AST less than or equal to 5x upper limit of normal

- Hgb more than 8.0 (may be a transfused value).

- Patients with a creatinine less than or equal to 2x upper limit of normal for age

- Pulse oximetry of more than 90% on room air

- Patients should have been off other investigational therapy for 4 weeks prior to entry
in this study.

- Patients with a Karnofsky/Lansky score of >/= 60

- Recovered from acute toxic effects of prior chemotherapy at least one week before
entering the study.

- Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 6 months after the study is concluded. The
male partner should use a condom.

- Informed consent explained to, understood and signed by patient/guardian.
Patient/guardian given a copy of informed consent.

Exclusion Criteria:

PROCUREMENT Exclusion

- Active infection with HIV, HTLV, HBV, HCV (can be pending at this time)

- History of solid organ transplant

TREATMENT Exclusion

- Pregnant or lactating due to unknown effects of this therapy on a fetus or lactation

- Severe active intercurrent infection.

- Current use of systemic corticosteroids >0.5 mg/kg/day

- Currently receiving any investigational agents or radiotherapy within 4 weeks prior to
entering the study.

- Patients with central nervous system involvement.

- History of allergic reactions attributed to nivolumab or any other checkpoint
inhibitors.

- Uncontrolled autoimmune disease needing systemic steroids or steroid sparing agents
except for hypothyroidism or type I diabetes.

- History of solid organ transplant

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Lipase more than 70U/ml
We found this trial at
2
sites
6621 Fannin St
Houston, Texas 77030
(832) 824-1000
Phone: 832-824-4647
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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6550 Fannin St
Houston, Texas 77030
(713) 790-3311
Phone: 713-441-6220
Houston Methodist Hospital Houston Methodist is comprised of a leading academic medical center in the...
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