EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus (EBV) + Nasopharyngeal Carcinoma (NPC) (CLANC)
To determine the safety of the combination of CD45 monoclonal antibody (Mab) followed by intravenous injection of EBV specific CTL in patients with nasopharyngeal cancer.
To compare the expansion, persistence and anti-tumor effects of the EBV specific CTL given after CD45 Mab administration with that observed in our first study.
To obtain preliminary information on the safety and response to an extended dosage regimen of EBV-specific CTL in patients, who have stable disease or a partial response after the initial dose of EBV-specific CTL.
|Nasopharyngeal Cancer EBV Infections||Biological: EBV specific CTL Infusion Biological: Anti CD45 monoclonal antibody||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Administration of EBV-Specific Cytotoxic T Lymphocytes Following CD45 Antibody to Patients With EBV Positive Nasopharyngeal Carcinoma|
- safety of autologous Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in combination with CD45 monoclonal antibody (Mab) in patients with nasopharyngeal cancer [ Time Frame: 6 weeks post infustion ]
- obtain information on the expansion, persistence and anti-tumor effects of EBV-specific CTL lines given after lymphodepletion with CD45 Mab in patients with nasopharyngeal cancer [ Time Frame: 12 months post infusion ]
- To obtain preliminary information on the safety and response to an extended dosage regimen of EBV-specific CTL in patients, who have stable disease or a partial response after the initial dose of EBV-specific CTL. [ Time Frame: 12 months post infusion ]
|Study Start Date:||September 2003|
|Study Completion Date:||April 2007|
|Primary Completion Date:||January 2007 (Final data collection date for primary outcome measure)|
Biological: EBV specific CTL Infusion
One injection at one of the following dose levels
Dose level I: 2x107/m2 Dose level II: 5x107/m2 Dose level III: 1x108/m2
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 reagents.
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00078546
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|The Methodist Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Stephen Gottschalk, MD||Baylor College of Medicine|