Administration of Epstein Barr Virus - Specific Cytotoxic T-Lymphocytes to Metastatic EBV-Positive Nasopharygneal Cancer (NPC-CTL)

July 8, 2015 updated by: University Health Network, Toronto

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)

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 cytotoxic 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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, the treatment of this cancer can lead to later complications, including other cancers, and if NPC relapses or spreads to other organs, the 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 in individuals, especially those with a compromised immune system. 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 cytotoxic 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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EBV-Specific CTLs and CD45 Mab
A dose escalation schema will be employed. Three to six patients will be treated at each of the following dose levels with EBV-Specific CTLs and CD45 Mab: Dose Level I: 2 x 10^7 cells/m2. Dose Level II: 5 x 10^7 cells/m2. Dose Level III: 1 x 10^8 cells/m2. Dose 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the safety of autologous EBV-specific CTLs in patients with nasopharyngeal cancer
Time Frame: 24 months
24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Lillian Siu, MD, University Health Network - Princess Margaret Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

August 1, 2009

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

June 25, 2008

First Submitted That Met QC Criteria

June 26, 2008

First Posted (Estimate)

June 27, 2008

Study Record Updates

Last Update Posted (Estimate)

July 10, 2015

Last Update Submitted That Met QC Criteria

July 8, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NPC-CTL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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