Epstein-Barr Virus Infections, Nasopharyngeal Neoplasms
Conditions
Keywords
histologically confirmed EBV+ NPC patients
Brief summary
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).
Interventions
DRUGMVA 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.
Sponsors
Chinese University of Hong Kong
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine safety and to characterise the toxicity profile of MVA-EBNA1/LMP2 vaccine | 4 years |
Secondary
| Measure | Time frame |
|---|---|
| To assess changes in levels of EBV genome levels in plasma | 4 Years |
| 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 |
Countries
Hong Kong
Outcome results
None listed