Vaccine Therapy in Treating Patients With Epstein-Barr Virus-Related Cancer

February 27, 2012 updated by: Cancer Research UK

A Phase I, Dose Escalation Trial of Recombinant Modified Vaccinia Ankara (MVA)-Based Vaccine Encoding Epstein-Barr Virus Target Antigens

RATIONALE: Vaccines made from a gene-modified virus 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 vaccine therapy in treating patients with Epstein-Barr virus and cancer.

Study Overview

Detailed Description

OBJECTIVES:

Primary

  • To determine safety and to characterize the toxicity profile of EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine in patients in remission having been treated conventionally for Epstein-Barr virus (EBV) and malignancy.
  • To describe changes in the frequency of functional T-cell responses to major histocompatibility complex (MHC) class I and II-restricted epitopes within EBNA1 and LMP2 in peripheral blood at sequential time-points before, during, and up to nine months after the vaccination course in these patients.

Secondary

  • To assess changes in levels of EBV genome in plasma in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine intradermally on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for immune function, biomarker, and pharmacological studies.

After completion of study treatment, patients are followed up at weeks 11 and 14, and at 6 months and 1 year.

Study Type

Interventional

Enrollment (Actual)

16

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

    • England
      • Birmingham, England, United Kingdom, B15 2TT
        • University of Birmingham
      • London, England, United Kingdom, SW3 6JJ
        • Royal Marsden - London
      • Manchester, England, United Kingdom, M20 4BX
        • Christie 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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignancy of a type typically associated with Epstein-Barr virus (EBV) latent infection meeting the following criteria:

    • The presence of EBV within the malignant cells has been demonstrated by immunohistochemistry for viral antigens or by EBER (EBV early RNA) in situ hybridization
  • Patients in remission from disease or with disease for which no standard treatment is appropriate, as defined by 1 of the following groups:

    • Have achieved a continuing complete response (CR) or unconfirmed CR
    • Residual masses at the site of treated disease that are not progressing (i.e., stable disease) and for which no standard therapy is recognized
    • Residual or recurrent disease that is low-volume and causing minimal or no symptoms and for which no standard therapy is recognized
  • Completed standard therapy for malignancy ≥ 12 weeks before trial entry

    • No more than 1 course of chemotherapy as treatment for EBV+ malignancy
  • No ongoing toxic manifestations of prior treatment, except alopecia or certain grade 1 toxicities at the discretion of the investigator and Cancer Research UK
  • No patients with active EBV+ cancer for whom evidence-based active treatment is available and likely to be offered to prolong life or relieve symptoms within 14 weeks of the first vaccination

PATIENT CHARACTERISTICS:

  • WHO performance status 0 or 1
  • Life expectancy ≥ 4 months
  • Lymphocyte count must satisfy 1 of the following criteria:

    • Greater than lower limit of the reference range in the investigator site
    • Greater than or equal to 0.5 x 10^9/L AND recovery from nadir of lymphocyte numbers following primary treatment for EBV+ malignancy, judged by no successive rises in lymphocyte count measured up to 3 successive occasions 3 weeks apart
  • Hemoglobin > 10.0 g/dL
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Serum alkaline phosphatase < 1.5 times ULN
  • ALT and/or AST < 1.5 times ULN
  • Calculated creatinine clearance > 50 mL/min (uncorrected value) OR isotope clearance measurement > 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during study and for 6 months after completion of study treatment
  • No known chronic active infection with hepatitis B, hepatitis C, or HIV
  • No history of anaphylaxis or severe allergy to vaccinations
  • No allergy to eggs or egg products
  • No ongoing active infection
  • No known splenic dysfunction
  • No concurrent active autoimmune disease
  • No prior NYHA class III or IV cardiac disease or concurrent congestive heart failure
  • No concurrent active skin diseases requiring therapy (i.e., psoriasis, eczema)
  • No other condition that, in the Investigator's opinion, would make the patient not a good candidate for this clinical trial

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior myeloablative therapy followed by an autologous or allogeneic hematopoietic stem cell transplant
  • More than 12 weeks since prior and no concurrent chemotherapy or radiotherapy
  • No splenectomy or splenic irradiation
  • No concurrent immunosuppressive medication, including corticosteroids

    • Long-term prophylactic use of inhaled corticosteroids allowed
  • No major thoracic and/or abdominal surgery within the past 4 weeks from which the patient has not yet recovered
  • No other concurrent anticancer or investigational drugs

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

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI CTCAE version 3.0)
Occurrence of local skin reactions considered related to the vaccination
Occurrence of drug-related systemic reactions (e.g., transient fever)
Demonstration by ELIspot assays of the frequency of T-lymphocytes recognizing major histocompatibility complex (MHC) class I and II-restricted epitopes within EBNA1 and LMP2 in peripheral blood at sequential time-points before, during, and up to 9 mo ...

Secondary Outcome Measures

Outcome Measure
Measurement of EBV-genome levels in plasma

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Neil M Stevens, MD, University of Birmingham

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

March 1, 2005

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

June 18, 2010

First Submitted That Met QC Criteria

June 18, 2010

First Posted (Estimate)

June 22, 2010

Study Record Updates

Last Update Posted (Estimate)

February 28, 2012

Last Update Submitted That Met QC Criteria

February 27, 2012

Last Verified

February 1, 2012

More Information

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.

Clinical Trials on Lymphoma

Clinical Trials on pharmacological study

3
Subscribe