Ignite Creation Date:
2024-05-05 @ 11:34 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00078546
Status:
COMPLETED
Last Update Posted:
2012-07-30
First Post:
2004-03-01
Brief Title:
EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus EBV Nasopharyngeal Carcinoma NPC
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Administration of EBV-Specific Cytotoxic T Lymphocytes Following CD45 Antibody to Patients With EBV Positive Nasopharyngeal Carcinoma
Status:
COMPLETED
Status Verified Date:
2012-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CLANC
Brief Summary:
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
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
Detailed Description:
Three different doses of CTL will be evaluated dose level I 2 x 10e7m2 dose level II 5 x 10e7m2 dose level III 1 x 10e8m2
Day 1 YTH 2454 800ugkg over 8 hr Day 2 YTH 2454 800ugkg over 8 hr Day 3 Rest Day 4-6 CTL Infusion provided CD45 Mab level 100 ugml
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
Cell administration
Patients will be pre-medicated with Diphenhydramine 1mgkg IV max 50 mg and Acetaminophen 10mgkg 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 1mgkg IV max 50 mg and Acetaminophen 10mgkg po max 650 mg 800ugkg 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 02-08 mg in the first hour and up to 10 mghr thereafter for a total infusion time of a maximum of 6 hrs A registered nurse and a physician must be readily available
Day 1 YTH 2454 800ugkg over 8 hr Day 2 YTH 2454 800ugkg over 8 hr Day 3 Rest Day 4-6 CTL Infusion provided CD45 Mab level 100 ugml
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
Cell administration
Patients will be pre-medicated with Diphenhydramine 1mgkg IV max 50 mg and Acetaminophen 10mgkg 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 1mgkg IV max 50 mg and Acetaminophen 10mgkg po max 650 mg 800ugkg 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 02-08 mg in the first hour and up to 10 mghr thereafter for a total infusion time of a maximum of 6 hrs A registered nurse and a physician must be readily available
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CLANC | None | None | None |