Administration of Neomycin Resistance Gene Marked EBV Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma
The investigators will take 60-70 ml (12 teaspoonfuls) of blood from the patient to make a B
cell line called a lymphoblastoid cell line or LCL by infecting the blood with a laboratory
strain of EBV called B95. The investigators 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. The investigators will then test the T
cells to make sure that they kill the EBV infected cells and not normal cells and freeze
Patients will be entered into one of three different dosing schedules being evaluated. Three
to six patients will be evaluated on each dosing schedule. Escalation will continue until
irreversible or life threatening side effects considered to be related to the T cells are
The cells will then be thawed and injected into the patients' vein over 10 minutes, after
pretreatment with Tylenol and Benadryl. Tylenol and Benadryl are given to prevent a possible
allergic reaction to the T cell administration. Initially, two doses of T cells will be
given two weeks apart. If after the second infusion there is a reduction in the size of the
patient's lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive
up to six additional doses of the T cells. All of the treatments will be given at Texas
Children's Hospital or the Methodist Hospital.
Patients will be followed in the clinic after the injections. At each visit about 10ml (2
teaspoonfuls) of blood will be taken every other week for 6 weeks after the injection and
then every 3 months for 1 year to monitor blood chemistry and hematology. To learn more
about the way the T cells are working and how long they last in the body, an extra 40 mls (8
teaspoonfuls) of blood will be taken before each infusion and then 24 hours after each
infusion, 3-4 days after each infusion and at 1, 2, 4, and 6 weeks post infusion and then at
3, 6, 9 and 12 months post infusion. The blood may be drawn from the central line at the
time of regular blood tests. This blood will be used to test for the frequency and activity
of EBV specific T cells. A total of at least 122 teaspoons (approximately 40 tablespoons) of
blood will be collected during participation in this study.
If the patient decide to withdraw at any time during the study both samples and data
collected during participation will be maintained.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The safety of two IV injections of auto EBV specific CTLs will be determined through adverse event measurement. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector.
Three patients will be enrolled at the first dose level and followed for six weeks after the second dose (which will constitute a course) for evaluation of any critical toxicity. The toxicity will be evaluated as per the NCI Common Toxicity criteria version 2.0.Any toxicity scored as Grade 3 or 4 according to this criteria will be classified as an adverse event. If no toxicity is observed in the first three patients then we will enroll another three patients at the next dose level. However, if toxicity is observed in no more than one out of the three patients then three more patients will be enrolled at the same dose level. Now if the toxicity is observed in no more than one out of the six patients then we will advance to the next dose level and enroll three new patients. If toxicity is observed in two or more patients out of six then the dose limiting toxicity (DLT) has been exceeded and the previous dose level will be considered as the maximum tolerated dose (MTD) level.
Catherine M. Bollard, MD
Baylor College of Medicine
United States: Food and Drug Administration
|Baylor College of Medicine||Houston, Texas 77030|
|Texas Children's Hospital||Houston, Texas|
|The Methodist Hospital||Houston, Texas 77030|