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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cancer Research UK
ClinicalTrials.gov Identifier:
NCT01147991
First received: June 18, 2010
Last updated: February 27, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
Head and Neck Cancer
Lymphoma
Lymphoproliferative Disorder
Nonneoplastic Condition
Biological: EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I, Dose Escalation Trial of Recombinant Modified Vaccinia Ankara (MVA)-Based Vaccine Encoding Epstein-Barr Virus Target Antigens

Resource links provided by NLM:


Further study details as provided by Cancer Research UK:

Primary Outcome Measures:
  • Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI CTCAE version 3.0) [ Designated as safety issue: Yes ]
  • Occurrence of local skin reactions considered related to the vaccination [ Designated as safety issue: Yes ]
  • Occurrence of drug-related systemic reactions (e.g., transient fever) [ Designated as safety issue: Yes ]
  • 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 ... [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measurement of EBV-genome levels in plasma [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: March 2005
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01147991

Locations
United Kingdom
University of Birmingham
Birmingham, England, United Kingdom, B15 2TT
Royal Marsden - London
London, England, United Kingdom, SW3 6JJ
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Sponsors and Collaborators
Cancer Research UK
Investigators
Principal Investigator: Neil M Stevens, MD University of Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT01147991     History of Changes
Other Study ID Numbers: CDR0000675266, CRUK-PH1-101, EUDRACT-2004-001931-46
Study First Received: June 18, 2010
Last Updated: February 27, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Cancer Research UK:
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Lymphoma
Lymphoproliferative Disorders
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Stomach Diseases

ClinicalTrials.gov processed this record on November 25, 2014