Modified Vaccinia Ankara (MVA) Vaccine Study

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

This is a phase I, dose escalation trial of MVA-EBNA1/LMP2 vaccine across a pre-defined range of doses in patients in remission having had an EBV+ nasopharyngeal carcinoma (NPC).

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Neoplasms; Epstein-Barr Virus Infections
• Intervention / Treatment: Drug: MVA Vaccine

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Department of Clinical Oncology, Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed NPC, in which the presence of EBV within the malignant cells has been demonstrated by (1) EBER (EBV early RNA) in situ hybridisation in more than 50% of the malignant cells, or (2) undifferentiated or poorly differentiated carcinoma histology in association with a raised serum titer of IgA to EBV VCA.
• Patients in remission from disease, ie complete response (CR) or unconfirmed complete response (CRu).
• Completion of standard therapy for malignancy at least 12 weeks before trial entry.
• Written informed consent and the ability of the patient to co-operate with treatment and follow up must be ensured and documented.
• Age greater than 18 years.
• World Health Organisation (WHO) performance status of 0 or 1
• Life expectancy of at least 4 months.

• Haematological and biochemical indices (these measurements must be performed within 28 days prior to the patient going on study):

  • Haemoglobin (Hb) > 10.0 g/dl
  • Lymphocytes > 1.0 x 109/L (or above the lower limit of normal range of institutional laboratory)
  • Neutrophils ≥ 1.5 x 109/L
  • Platelets (Plts) ≥ 100 x 109/L
  • baseline liver function tests :
  • Serum bilirubin ≤ 1.5 x upper normal limit
  • Serum alkaline phosphatase, alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) < 1.5 x ULN.
  • baseline renal function test:
  • calculated creatinine clearance > 50ml/min Female patients of child-bearing potential are eligible, provided they have a negative pregnancy test prior to enrolment and agree to use appropriate medically approved contraception during the study up to six months after the last vaccination.
• Male patients must agree to use appropriate medically approved contraception during the study up to six months after the last vaccination.

Exclusion Criteria:

• Receiving current chemotherapy or radiotherapy, or received within 12 weeks of trial entry.
• Known chronic active infection with Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
• Current active autoimmune disease.
• Current active skin diseases requiring therapy (psoriasis, eczema etc).
• Ongoing active infection.
• History of anaphylaxis or severe allergy to vaccination.
• Allergy to eggs or egg products.
• Previous myeloablative therapy followed by an autologous or allogeneic haematopoietic stem cell transplant.
• Patients who have had a splenectomy or splenic irradiation, or with known splenic dysfunction.
• Receiving current immunosuppressive medication, including corticosteroids.
• Pregnant and lactating women.
• Ongoing toxic manifestations of previous treatment. Exceptions to this are alopecia or certain Grade 1 toxicities which in the opinion of the Investigator and Cancer Research UK should not exclude the patient.
• Major thoracic and/or abdominal surgery in the preceding four weeks from which the patient has not yet recovered.
• Patients with any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
• Concurrent congestive heart failure or prior history of class III/ IV cardiac disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MVA Vaccine	Drug: MVA Vaccine; The starting dose will be 5 x 107 plaque forming units (pfu) given by intradermal vaccination. Cohorts of three patients will receive escalating doses of the vaccine (100%, 100%, 67% and 50%). The dose escalation scheme is 5 x 107 pfu, 1 x 108 pfu, 2 x 108 pfu, 3.3 x 108 pfu, 5 x 108pfu. This will be dependant on toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine safety and to characterise the toxicity profile of MVA-EBNA1/LMP2 vaccine	4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To describe changes in the frequency of functional T-cell responses to 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.	4 years
To assess changes in levels of EBV genome levels in plasma	4 Years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Anthony TC Chan, MD, FRCP, Department of Clinical Oncology, The Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: December 8, 2010
• First Submitted That Met QC Criteria: December 8, 2010
• First Posted (Estimate): December 9, 2010

Study Record Updates

• Last Update Posted (Estimate): December 22, 2011
• Last Update Submitted That Met QC Criteria: December 21, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: histologically confirmed EBV+ NPC patients
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Poxviridae Infections; Nasopharyngeal Neoplasms; Epstein-Barr Virus Infections; Vaccinia
• Other Study ID Numbers: VAC002