Lymphoproliferative Disorder
Conditions
Keywords
post-transplant lymphoproliferative disorder
Brief summary
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
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.
Interventions
BIOLOGICALInactivated EBV-infected vaccine
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Vaccine as Assessed by T-cell Responses | Up to 67 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Associated With the Vaccine | Up to 5 years | 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. |
| Prevention of Primary Epstein-Barr Virus (EBV) Infection | Up to 5 years | 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. |
Countries
United States
Participant flow
Pre-assignment details
One subject on the EBV seronegative arm was a screen failure. One EBV seronegative subject was not assigned to intervention arm due to physician decision. Seven EBV seropositive subjects were not assigned to intervention arm: three due to physician decision; one due to loss of follow-up; one due to death; and two due to subject withdrawal.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Inactivated EBV-infected vaccine | 2 |
| 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.
Inactivated EBV-infected vaccine | 12 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 3 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | EBV Seropositive | Total | EBV Seronegative |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 12 Participants | 2 Participants |
| Age, Continuous | 54 years | 54 years | 38 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 12 Participants | 14 Participants | 2 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 4 / 12 |
| other Total, other adverse events | 1 / 2 | 9 / 12 |
| serious Total, serious adverse events | 1 / 2 | 2 / 12 |
Outcome results
Primary
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.
Time frame: Up to 67 days
Population: T-cell responses were uninterpretable on lab analysis; therefore, data was not collected to assess this outcome measure.
Secondary
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.
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EBV Seronegative | Adverse Events Associated With the Vaccine | 0 Participants |
| EBV Seropositive | Adverse Events Associated With the Vaccine | 0 Participants |
Secondary
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.
Time frame: Up to 5 years
Population: Only one participant met the criteria described in the outcome description. This participant was never tested post-transplant for EBV, so no data was collected for this outcome measure.