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EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus (EBV) + Nasopharyngeal Carcinoma (NPC) (CLANC)

Primary Purpose

Nasopharyngeal Cancer, EBV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
EBV specific CTL Infusion
Anti CD45 monoclonal antibody
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Cancer focused on measuring EBV, NASOPHARYNGEAL, CARCINOMA, EBV POSITIVE NASOPHARYNGEAL CARCINOMA

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. .

Sites / Locations

  • Texas Children's Hospital
  • The Methodist Hospital

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
March 1, 2004
Last Updated
July 27, 2012
Sponsor
Baylor College of Medicine
Collaborators
The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00078546
Brief Title
EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus (EBV) + Nasopharyngeal Carcinoma (NPC)
Acronym
CLANC
Official Title
Administration of EBV-Specific Cytotoxic T Lymphocytes Following CD45 Antibody to Patients With EBV Positive Nasopharyngeal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
September 2003 (undefined)
Primary Completion Date
January 2007 (Actual)
Study Completion Date
April 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
Collaborators
The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Cancer, EBV Infections
Keywords
EBV, NASOPHARYNGEAL, CARCINOMA, EBV POSITIVE NASOPHARYNGEAL CARCINOMA

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
EBV specific CTL Infusion
Intervention Description
One injection at one of the following dose levels Dose level I: 2x107/m2 Dose level II: 5x107/m2 Dose level III: 1x108/m2
Intervention Type
Biological
Intervention Name(s)
Anti CD45 monoclonal antibody
Other Intervention Name(s)
YTH 24/54
Intervention Description
400ug/kg over 6 to 8 hr for 4 days
Primary Outcome Measure Information:
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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. .
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Gottschalk, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18971421
Citation
Louis CU, Straathof K, Bollard CM, Gerken C, Huls MH, Gresik MV, Wu MF, Weiss HL, Gee AP, Brenner MK, Rooney CM, Heslop HE, Gottschalk S. Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients. Blood. 2009 Mar 12;113(11):2442-50. doi: 10.1182/blood-2008-05-157222. Epub 2008 Oct 29.
Results Reference
derived

Learn more about this trial

EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus (EBV) + Nasopharyngeal Carcinoma (NPC)

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