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

Phase 1
18 Years
Not Enrolling
Gastric Cancer, Head and Neck Cancer, Lymphoma, Lymphoproliferative Disorder, Nonneoplastic Condition

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Trial Information

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



- 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

- 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.


- 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

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

Inclusion Criteria


- 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

- 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


- 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


- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI CTCAE version 3.0)

Safety Issue:


Principal Investigator

Neil M Stevens, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Birmingham


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

March 2005

Completion Date:

April 2011

Related Keywords:

  • Gastric Cancer
  • Head and Neck Cancer
  • Lymphoma
  • Lymphoproliferative Disorder
  • Nonneoplastic Condition
  • Epstein-Barr virus infection
  • stage I nasopharyngeal cancer
  • stage II nasopharyngeal cancer
  • stage I adult Hodgkin lymphoma
  • stage II adult Hodgkin lymphoma
  • post-transplant lymphoproliferative disorder
  • stage I gastric cancer
  • stage II gastric cancer
  • adult nasal type extranodal NK/T-cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • stage I adult Burkitt lymphoma
  • contiguous stage II adult Burkitt lymphoma
  • contiguous stage II adult immunoblastic large cell lymphoma
  • stage I adult immunoblastic large cell lymphoma
  • Head and Neck Neoplasms
  • Lymphoma
  • Lymphoproliferative Disorders
  • Stomach Neoplasms
  • Lymphoma, Large-Cell, Immunoblastic