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

NCT01147991 | Completed Phase 1

• 3 other identifiers: CDR0000675266CRUK-PH1-101EUDRACT-2004-001931-46
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Measurement of EBV-genome levels in plasma

Interventions

EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine BIOLOGICAL

laboratory biomarker analysis OTHER

pharmacological study OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (3)

University of Birmingham

Birmingham, England, B15 2TT, United Kingdom

Location

Royal Marsden - London

London, England, SW3 6JJ, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Stomach Neoplasms; Head and Neck Neoplasms; Lymphoma; Lymphoproliferative Disorders; Epstein-Barr Virus Infections; Nasopharyngeal Neoplasms; Hodgkin Disease; Lymphoma, Extranodal NK-T-Cell; Immunoblastic Lymphadenopathy; Burkitt Lymphoma; Lymphoma, Large-Cell, Immunoblastic

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphadenopathy; Lymphoma, B-Cell

Study Officials

• Neil M Stevens, MD

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2010
• First Posted: June 22, 2010
• Study Start: March 1, 2005
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: February 28, 2012

Record last verified: 2012-02

Locations

GB (3)