Modified Vaccinia Ankara (MVA) Vaccine Study

Study Overview
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Brief Summary
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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).

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

Conditions
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Nasopharyngeal Neoplasms, Epstein-Barr Virus Infections

Intervention / Treatment
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* Drug: MVA Vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MVA Vaccine<br> | Drug: MVA Vaccine<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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histologically confirmed EBV+ NPC patients