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Administration of EBV-Specific Cytotoxic T Lymphocytes Following CD45 Antibody to Patients With EBV Positive Nasopharyngeal Carcinoma

Phase 1
Not Enrolling
Nasopharyngeal Cancer, EBV Infections

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Trial Information

Administration of EBV-Specific Cytotoxic T Lymphocytes Following CD45 Antibody to Patients With EBV Positive Nasopharyngeal Carcinoma

Three different doses of CTL will be evaluated: dose level I: 2 x 10e7/m2; dose level II: 5
x 10e7/m2; dose level III: 1 x 10e8/m2

Day 1 YTH 24/54 800ug/kg over 8 hr; Day 2 YTH 24/54 800ug/kg over 8 hr; Day 3 Rest; Day 4-6
CTL Infusion (provided CD45 Mab level <100 ug/ml).

Generation of EBV-specific CTL

After consent on the separate procurement protocol for CTL preparation the patient will
donate up to 60-70cc of peripheral blood. 10-20cc of this will be used for the establishment
of an EBV transformed lymphoblastoid cell line (EBV-LCL) by infection with virus produced
from the B95-8 master cell line. The EBV-LCLs will take approximately four to six weeks to
establish. 30-40cc of peripheral blood will be used to generate EBV specific CTLs. The CTL
line will be prepared by co-cultivation of the irradiated EBV-LCL with patient PBMC. After
establishment, the CTL lines will be checked for identity, phenotype and microbiological
culture and cryopreserved prior to administration according to SOPs. The antigen specificity
of each CTL line will be determined in cytotoxicity assay and when possible with tetramer

CD45 monoclonal antibodies

Anti-CD45 is a combination in equal amounts (weight for volume) of two monoclonal antibodies
that are directed to non-overlapping epitopes on human CD45. It is a purified, concentrated,
and sterile gamma globulin, primarily monomeric IgG, produced from the supernatant of the
two rat IgG2b hybridoma clones, YTH 24 and YTH 54. The hybridomas were produced as fusions
between splenocytes from DA rats immunized with human leukocytes and the rat myeloma line
Y3. The combination of the two MAbs exerts a synergistic effect in vitro on
complement-mediated cytotoxicity of white cells and it has been demonstrated to clear almost
all passenger leukocytes from donor kidneys before transplant. Anti-CD45 Mabs have been made
under cGMP conditions at the Therapeutic Antibody Center at Oxford and at Baylor College of
Medicine and will pass the safety tests required by the FDA.

Cell administration

Patients will be pre-medicated with Diphenhydramine 1mg/kg IV (max 50 mg) and Acetaminophen
10mg/kg po (max 650 mg). EBV specific T cells will be given by intravenous injection over
1-10 minutes through either a peripheral or a central line. Outpatients may be treated in
the clinic. Monitoring will be undertaken according to institutional standards for
administration of blood products with the exception that the injection will be given by a
physician. Anti-emetics in appropriate dosage for each patient will be prescribed as
necessary. Patients will receive supportive care for acute or chronic toxicity, including
blood components or antibiotics, and other intervention as appropriate.

Antibody administration

Patients will be pre-medicated with Diphenhydramine 1mg/kg IV (max 50 mg) and Acetaminophen
10mg/kg po (max 650 mg). 800ug/kg CD45 Mabs will be given as 2 daily intravenous infusions
over 8 hours. The antibody aliquot to be infused will arrive in the treatment area
hand-carried by the attending physician or appointed designate. The antibody aliquot will be
diluted in minimal amounts of normal saline. The resulting solution is stable for 24 hours.
The antibody solution is administered by a syringe pump in incremental doses, 0.2-0.8 mg in
the first hour and up to 10 mg/hr thereafter, for a total infusion time of a maximum of 6
hrs. A registered nurse and a physician must be readily available.

Inclusion Criteria:

- Any patient with EBV positive NPC, in relapse or with primary resistant disease

- Life expectancy of more than 6 weeks.

- No severe intercurrent infection

- Patient, parent/guardian able to give informed consent

- Bilirubin less than 2x normal

- SGOT less than 3x normal,

- Hgb higher than 8.0 g/L

- Creatinine less than 2x normal for age

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

- Karnofsky score of over or equal to 50.

Exclusion Criteria:

Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this
research. The male partner should use a condom.

Note: Patients who would be excluded from the protocol strictly for laboratory
abnormalities can be included at the investigator's discretion after approval by the CCGT
Protocol Review Committee and the FDA reviewer.


Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

safety of autologous Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in combination with CD45 monoclonal antibody (Mab) in patients with nasopharyngeal cancer

Outcome Time Frame:

6 weeks post infustion

Safety Issue:


Principal Investigator

Stephen Gottschalk, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine


United States: Food and Drug Administration

Study ID:




Start Date:

September 2003

Completion Date:

April 2007

Related Keywords:

  • Nasopharyngeal Cancer
  • EBV Infections
  • EBV
  • Carcinoma
  • Epstein-Barr Virus Infections
  • Nasopharyngeal Neoplasms



Texas Children's Hospital Houston, Texas  
The Methodist Hospital Houston, Texas  77030