Vaccine Therapy For Patients Being Considered For Organ Transplant Who Are at Risk For PTLD

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a person's white blood cells may help the body build an effective immune response. PURPOSE: This phase I trial is studying the side effects of vaccine therapy in treating patients who are being considered for solid organ transplant who are at risk for post-transplant lymphoproliferative disorder.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of photochemically-treated autologous Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell vaccine in generating an EBV-specific T-cell and antibody response in EBV-negative patients or in boosting the response in EBV-positive patients who are being considered for a solid organ transplant and are at high risk for post-transplant lymphoproliferative disorder. Determine adverse events associated with this vaccine in these patients. Determine the ability of the vaccine to protect from EBV primary infection in EBV-seronegative patients during the time course of the study. OUTLINE: This is a nonrandomized, pilot study. Patients are stratified according to Epstein-Barr virus (EBV) status (seropositive vs seronegative). Patients receive photochemically-treated autologous EBV-transformed B-lymphoblastoid cell vaccine intradermally once in weeks 0 and 4. After completion of study treatment, patients are followed periodically for up to 5 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Official Title
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Vaccination of Patients at High Risk for Post-Transplant Lymphoproliferative Disorder With a Photochemically Inactivated EBV-Infected B-Cell Vaccine

Conditions
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Lymphoproliferative Disorder

Intervention / Treatment
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* Biological: Inactivated EBV-infected vaccine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Being considered for a solid organ transplant At high risk for post-transplant lymphoproliferative disorder PATIENT CHARACTERISTICS: Body weight ≥ 25 kg Karnofsky performance status 50-100% OR Lansky performance status 50-100% Not pregnant Negative pregnancy test Fertile patients must use contraception during and for 2 months after completion of study treatment Hemoglobin ≥ 8 g/dL (erythropoietin allowed) No history of autoimmune disease, including any of the following: Systemic lupus erythematosus Sarcoidosis Rheumatoid arthritis Glomerulonephritis Vasculitis No primary immunodeficiency No HIV positivity PRIOR CONCURRENT THERAPY: No corticosteroids for 1 month before and for 1 month after the first study vaccination, except for the following: Physiologic steroid dosing (≤ 20 mg/day of prednisone or steroid equivalent) for adrenal insufficiency Inhaled steroids
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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBV Seronegative<br>Inactivated EBV-infected vaccine given at Week 0 and Week 4. This arm included all participants who were negative for Epstein-Barr Virus (EBV) at baseline. | Biological: Inactivated EBV-infected vaccine<br> <br> |
| Experimental: EBV Seropositive<br>Inactivated EBV-infected vaccine given at Week 0 and Week 4. This arm included all participants who were positive for Epstein-Barr Virus (EBV) at baseline. | Biological: Inactivated EBV-infected vaccine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Vaccine as Assessed by T-cell Responses | Percentage of participants with T-cell responses. For participants who were EBV-seronegative at enrollment, a response is defined as the appearance of EBV-specific T-cells at one month after the second injection. For participants who were EBV-seropositive at enrollment, a response is defined as a two-fold increase over baseline in the frequency of CD8+ T-cells responding to EBV latency antigens at any point during the first 67 days following the first injection. | Up to 67 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events Associated With the Vaccine | Number of participants who received at least one vaccination and experienced at least one grade 3-4 adverse event by CTCAE 2.0 that was attributed to protocol therapy. | Up to 5 years | 
| Prevention of Primary Epstein-Barr Virus (EBV) Infection | Number of participants who were EBV-seronegative at baseline, received at least one vaccination, subsequently received a solid organ transplant (not part of this protocol), and did not develop a primary EBV infection. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post-transplant lymphoproliferative disorder