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

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

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.

Study Overview

• Status: Terminated
• Conditions: Lymphoproliferative Disorder
• Intervention / Treatment: Biological: Inactivated EBV-infected vaccine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EBV Seronegative; 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
Experimental: EBV Seropositive; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2003
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: January 16, 2006
• First Submitted That Met QC Criteria: January 16, 2006
• First Posted (Estimate): January 18, 2006

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: post-transplant lymphoproliferative disorder
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoproliferative Disorders
• Other Study ID Numbers: J0216; P30CA006973 (U.S. NIH Grant/Contract); NA_00046066 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO