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

Primary Purpose

Gastric Cancer, Head and Neck Cancer, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine
laboratory biomarker analysis
pharmacological study
Sponsored by
Cancer Research UK
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Birmingham
  • Royal Marsden - London
  • Christie Hospital

Outcomes

Primary Outcome Measures

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

Measurement of EBV-genome levels in plasma

Full Information

First Posted
June 18, 2010
Last Updated
February 27, 2012
Sponsor
Cancer Research UK
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1. Study Identification

Unique Protocol Identification Number
NCT01147991
Brief Title
Vaccine Therapy in Treating Patients With Epstein-Barr Virus-Related Cancer
Official Title
A Phase I, Dose Escalation Trial of Recombinant Modified Vaccinia Ankara (MVA)-Based Vaccine Encoding Epstein-Barr Virus Target Antigens
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cancer Research UK

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Head and Neck Cancer, Lymphoma, Lymphoproliferative Disorder, Nonneoplastic Condition
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI CTCAE version 3.0)
Title
Occurrence of local skin reactions considered related to the vaccination
Title
Occurrence of drug-related systemic reactions (e.g., transient fever)
Title
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 Measure Information:
Title
Measurement of EBV-genome levels in plasma

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neil M Stevens, MD
Organizational Affiliation
University of Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Birmingham
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Facility Name
Royal Marsden - London
City
London
State/Province
England
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Christie Hospital
City
Manchester
State/Province
England
ZIP/Postal Code
M20 4BX
Country
United Kingdom

12. IPD Sharing Statement

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

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