A Phase I Trial Evaluating the Administration of Epstein Barr Virus (EBV)-Specific Cytotoxic T-Lymphocytes (CTLs) to Patients With Recurrent or Metastatic EBV-Positive Nasopharygneal Cancer (NPC) - Full Text View

Sponsored by:	University Health Network, Toronto
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00706316

Purpose

Nasopharyngeal cancer (NPC) is a cancer that starts at the back of the nose. Without distant spread, NPC is sensitive to radiotherapy and chemotherapy; however, if NPC relapses or spreads to other organs, treatment options are limited. This grant proposes to evaluate the safety and tolerability of a novel treatment for patients with NPC that has either relapsed or spread to distant organs. Epstein-Barr Virus (EBV) is known to play a role in the development of NPC, and studies have shown that NPC tumor cells express proteins that are related to EBV. Some of these proteins can trigger a response from the immune system, specifically the activation of cytototoxic T lymphocytes (CTLs), a type of immune cell that might exert anti-tumor effects. In this project, we will take blood from NPC patients, generate CTLs targeted against EBV, and re-infuse these back into patients in an attempt to achieve anti-tumor activity. Patients will also receive an antibody called CD45 Mab prior to CTL infusion in order to allow for better expansion of the infused CTLs in the patients.

Condition	Intervention	Phase
Nasopharyngeal Cancer	Biological: EBV-Specific CTLs and CD45 Mab	Phase I

MedlinePlus related topics: Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Open Label, Active Control, Single Group Assignment, Safety Study
Official Title:	A Phase I Trial Evaluating the Administration of Epstein Barr Virus (EBV)-Specific Cytotoxic T-Lymphocytes (CTLs) to Patients With Recurrent or Metastatic EBV-Positive Nasopharygneal Cancer (NPC)

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

To determine the safety of autologous EBV-specific CTLs in patients with nasopharyngeal cancer [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To obtain information on the expansion, persistence and anti-tumor effects of EBV-specific CTL lines in patients with nasopharyngeal cancer [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	25
Study Start Date:	December 2007
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental A dose escalation schema will be employed. Three to six patients will be treated at each of the following dose levels:Dose Level I: 2 x 10^7 cells/m2Dose Level II: 5 x 10^7 cells/m2Dose Level III: 1 x 10^8 cells/m2Dose escalation decisions will be made after review of the data from the current dose level. There will be no intra-patient escalation. An additional 6-10 patients with measurable disease will be treated at the recommended phase II dose to expand the experience at this dose level.	Biological: EBV-Specific CTLs and CD45 Mab One time infusion (IV) at one of the following dose levels: Dose level I: 5 x 107 cells/m2 Dose level II: 1 x 108 cells/m2 Dose level III: 2 x 108 cells/m2

Arms

Assigned Interventions

1: Experimental

A dose escalation schema will be employed. Three to six patients will be treated at each of the following dose levels:Dose Level I: 2 x 10^7 cells/m2Dose Level II: 5 x 10^7 cells/m2Dose Level III: 1 x 10^8 cells/m2Dose escalation decisions will be made after review of the data from the current dose level. There will be no intra-patient escalation. An additional 6-10 patients with measurable disease will be treated at the recommended phase II dose to expand the experience at this dose level.

Biological: EBV-Specific CTLs and CD45 Mab

One time infusion (IV) at one of the following dose levels:

Dose level I: 5 x 107 cells/m2

Dose level II: 1 x 108 cells/m2

Dose level III: 2 x 108 cells/m2

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Any patient with EBV positive NPC, with recurrent and/or metastatic disease
Patients with a life expectancy > 3 months.
Patients with an ECOG performance status of 0, 1 or 2
No severe intercurrent infection.
Patients who are able to give informed consent.
Patients with:
- bilirubin <2x normal,
- SGOT (AST) and SGPT (ALT) <3x normal,
- Hgb >80 g/L,
- absolute neutrophil count (ANC) > 1.5 x 109/L,
- and platelets > 100 x 109/L.
Patients with a creatinine <2x normal for age
Patients should have been off any chemotherapy or other investigational therapy for at least 4 weeks prior to entry in this study.
Patients should have completed any prior radiation therapy for at least 3 weeks prior to entry in this study. Exception may be made, however, for low-dose, non-myelosuppressive radiotherapy, but this must be discussed with Principal Investigator(s).
All patients must have measurable disease, with minimum indicator lesions size as follows:
- CT scan > 2 cm (or > 1 cm if spiral CT scan is used)
- Ultrasound > 2 cm
- Chest x-ray > 2 cm
- Physical exam > 1 cm (skin lesions, nodes, soft tissue masses)

Exclusion Criteria:

Patients with a life expectancy of < 3 months.
Patients with an ECOG performance status of >2.
Patients with a severe intercurrent infection.
Patients unable or unwilling to give informed consent.
Patients with a bilirubin >2x normal.
SGOT (AST) and SGPT (ALT) >3x normal.
Patients with a creatinine >2x normal for age
Patients with Hgb < 80 g/L, absolute neutrophil count (ANC) < 1.5 x 109/L, and platelets < 100 x 109/L.
Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. Lactating women are excluded from this study. Patients and their partners must use an effective birth control method during the study and for 6 months after. Effective birth control methods are: total abstinence, oral contraceptives, intrauterine devices, contraceptive implants under the skin or contraceptive injections. If one of these methods cannot be used, contraceptive foam with a condom is allowed. The male partner should use a condom.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706316

Contacts

Contact: Lillian Siu

416 946 2911

lillian.siu@uhn.on.ca

Locations

Canada, Ontario
Princess Margaret Hospital	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Lillian Siu 416 946 2911 lillian.siu@uhn.on.ca
Principal Investigator: Lillian Siu, MD
Principal Investigator: Armand Keating, MD

Sponsors and Collaborators

University Health Network, Toronto

Investigators

Principal Investigator:

Lillian Siu, MD

University Health Network - Princess Margaret Hospital

More Information

Responsible Party:	University Health Network, Princess Margaret Hospital ( Dr. Lillian Siu )
Study ID Numbers:	NPC-CTL, OCRN #03-NOV-0422
Study First Received:	June 25, 2008
Last Updated:	June 26, 2008
ClinicalTrials.gov Identifier:	NCT00706316
Health Authority:	Canada: Health Canada

Keywords provided by University Health Network, Toronto:

Nasopharygneal Cancer
Epstein Barr Virus
(EBV)-Specific Cytotoxic T-Lymphocytes

Recurrent
Metastatic
EBV-Positive Nasopharygneal Cancer

Study placed in the following topic categories:

Virus Diseases
Nasopharyngeal carcinoma
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms

Pharyngeal Neoplasms
Stomatognathic Diseases
Pharyngeal Diseases
Nasopharyngeal Neoplasms
Recurrence

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases

ClinicalTrials.gov processed this record on January 16, 2009