Laboratory-Treated Autologous T-Lymphocytes in Treating Patients With High-Risk, Refractory, or Recurrent Epstein-Barr Virus-Positive Nasopharyngeal Cancer - Full Text View

Sponsors and Collaborators:	Baylor College of Medicine National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00682864

Purpose

RATIONALE: Some types of nasopharyngeal cancer are associated with Epstein-Barr virus. White blood cells that are treated in the laboratory with Epstein-Barr virus antigens may help the body build an effective immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated autologous T-lymphocytes in treating patients with high-risk, refractory, or recurrent Epstein-Barr virus-positive nasopharyngeal cancer.

Condition	Intervention	Phase
Head and Neck Cancer	Biological: autologous LMP1-/LMP2- specific cytotoxic T-lymphocytes Genetic: polymerase chain reaction Other: immunoenzyme technique Other: laboratory biomarker analysis	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Administration Of LMP1-And LMP2-Specific Cytotoxic T-Lymphocytes To Patients With EBV-Positive Nasopharyngeal Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]
Frequency of T-cells specific for Epstein-Barr virus antigens and CMV (or adenovirus) as measured by multimer and enzyme-linked immunospot (Elispot) assays [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate as measured by RECIST criteria [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	June 2007
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To determine the safety of autologous LMP1- and LMP2-specific cytotoxic T-lymphocytes in patients with high-risk, refractory, or recurrent Epstein-Barr virus-positive nasopharyngeal carcinoma.
To obtain information on the expansion, persistence, and anti-tumor effects of this treatment regimen in these patients.

OUTLINE: Peripheral blood samples are collected to generate dendritic cells (DC). The DCs are cultured with sargramostim (GM-CSF) and interleukin-4 (IL-4), transduced with recombinant adenovirus encoding non-toxic LMP1 and LMP2, and matured with recombinant IL-4, GM-CSF, TNF-α, and prostaglandin (PGE-1) to stimulate cytotoxic T-lymphocytes (CTL). An Epstein-Barr virus (EBV)-transformed lymphoblastoid B-cell line is established and LMP1- and LMP2-specific CTL are generated.

Patients receive autologous LMP1- and LMP2-specific CTL IV over 1-10 minutes on days 0 and 14. Cohorts of patients receive escalating doses of autologous LMP1- and LMP2-specific CTL until the maximum tolerated dose (MTD) is determined. A total of 16 patients are treated at the MTD.

Patients undergo blood sample collection at baseline and periodically during study for immune function studies.

Samples are analyzed for evaluation of phenotype; frequency of T cells specific for EBV antigens and control antigens (e.g., CMV or adenovirus) by multimer analysis, enzyme-linked immunospot (Elispot), or CTL precursor assays; specificity of EBV responses by cytotoxicity assays (when appropriate); and EBV DNA persistence by polymerase chain reaction. Blood samples are also used to determine concentration of molecules that modulate immune responses such as cytokines or chemokines.

After completion of study treatment, patients are followed periodically for up to 12 months.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of nasopharyngeal carcinoma meeting one of the following criteria:
- In first or subsequent relapse
- Primary refractory disease
- High-risk (T3 or T4, or node positive) disease
Tumor tissue positive for Epstein-Barr virus

PATIENT CHARACTERISTICS:

Life expectancy > 6 weeks
Karnofsky performance status 50-100% (≥ 16 years of age) OR Lansky performance status 50-100% (< 16 years of age)
Bilirubin < 2 times normal*
SGOT < 3 times normal*
Hemoglobin > 8.0*
Creatinine < 2 times normal for age*
Not pregnant
Negative pregnancy
Fertile patients must use effective contraception
No severe concurrent infection NOTE: *Patients who would be excluded from the study strictly due to laboratory abnormalities may be eligible at the investigator's discretion after approval by the CCGT Protocol Review Committee and the FDA reviewer.

PRIOR CONCURRENT THERAPY:

At least 1 month since prior investigational therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00682864

Locations

United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Trials Office - Dan L. Duncan Cancer Center at Baylor 713-798-1297
Methodist Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Yu-Feng Lin 832-824-4258
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Recruiting
Houston, Texas, United States, 77030-2399
Contact: Yu-Feng Lin 832-824-4258

Sponsors and Collaborators

Baylor College of Medicine

National Cancer Institute (NCI)

Investigators

Study Chair:	Stephen Gottschalk, MD	Baylor College of Medicine
Principal Investigator:	Helen E. Heslop, MD	Baylor College of Medicine

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000596241, BCM-H-21000
Study First Received:	May 21, 2008
Last Updated:	June 9, 2009
ClinicalTrials.gov Identifier:	NCT00682864 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent lymphoepithelioma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
stage II lymphoepithelioma of the nasopharynx
stage II squamous cell carcinoma of the nasopharynx

stage III lymphoepithelioma of the nasopharynx
stage III squamous cell carcinoma of the nasopharynx
stage IV lymphoepithelioma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx

Study placed in the following topic categories:

Nasopharyngeal Carcinoma
Otorhinolaryngologic Neoplasms
Otorhinolaryngologic Diseases
Pharyngeal Neoplasms
Squamous Cell Carcinoma
Pharyngeal Diseases
Recurrence

Nasopharyngeal Neoplasms
Carcinoma
Virus Diseases
Head and Neck Neoplasms
Epidermoid Carcinoma
Stomatognathic Diseases
Carcinoma, Squamous Cell

Additional relevant MeSH terms:

Neoplasms
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Neoplasms by Site
Head and Neck Neoplasms

Nasopharyngeal Diseases
Pharyngeal Neoplasms
Stomatognathic Diseases
Pharyngeal Diseases
Nasopharyngeal Neoplasms

ClinicalTrials.gov processed this record on September 10, 2009