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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00278200
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 23
• Location: 1
• Arms: 2
• Actual Duration (Months): 115
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoproliferative Disorder	Biological: Inactivated EBV-infected vaccine	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Vaccination of Patients at High Risk for Post-Transplant Lymphoproliferative Disorder With a Photochemically Inactivated EBV-Infected B-Cell Vaccine
• Actual Study Start Date: Jan 1, 2003
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Richard F Ambinder, MD, PhD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00278200
• Other Study ID Numbers: J0216; P30CA006973; NA_00046066
• First Posted: Jan 18, 2006
• Last Update Posted: Feb 26, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: post-transplant lymphoproliferative disorder
• Additional relevant MeSH terms: Lymphoproliferative Disorders

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	EBV Seronegative	EBV Seropositive
Arm/Group Description	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 given at Week 0 and Week 4. This arm included all participants who were positive for Epstein-Barr Virus (EBV) at baseline.
Period Title: Overall Study
STARTED	2	12
COMPLETED	1	8
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	EBV Seronegative	EBV Seropositive	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	2	12	14
Age (Count of Participants)
<=18 years	0 0%	2 16.7%	2 14.3%
Between 18 and 65 years	2 100%	10 83.3%	12 85.7%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	38	54	54
Sex: Female, Male (Count of Participants)
Female	0 0%	8 66.7%	8 57.1%
Male	2 100%	4 33.3%	6 42.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	2 100%	12 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Efficacy of Vaccine as Assessed by T-cell Responses
Description	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

Outcome Measure Data

Analysis Population Description

T-cell responses were uninterpretable on lab analysis; therefore, data was not collected to assess this outcome measure.

Arm/Group Title	EBV Seronegative	EBV Seropositive
Arm/Group Description	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	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
Measure Participants	0	0

2. Secondary Outcome

Title	Adverse Events Associated With the Vaccine
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EBV Seronegative	EBV Seropositive
Arm/Group Description	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	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
Measure Participants	2	12
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Prevention of Primary Epstein-Barr Virus (EBV) Infection
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	EBV Seronegative
Arm/Group Description	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
Measure Participants	0

Adverse Events

Time Frame	Up to 5 years
Arm/Group Title	EBV Seronegative		EBV Seropositive
Arm/Group Description	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 given at Week 0 and Week 4. This arm included all participants who were positive for Epstein-Barr Virus (EBV) at baseline.
All Cause Mortality
	EBV Seronegative		EBV Seropositive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		4/12 (33.3%)
Serious Adverse Events
	EBV Seronegative		EBV Seropositive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		2/12 (16.7%)
Infections and infestations
Bacteremia	0/2 (0%)	0	1/12 (8.3%)	1
Peritonitis	0/2 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Acute lung injury	0/2 (0%)	0	1/12 (8.3%)	1
Respiratory distress	1/2 (50%)	1	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	EBV Seronegative		EBV Seropositive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		9/12 (75%)
Gastrointestinal disorders
Nausea	0/2 (0%)	0	1/12 (8.3%)	1
Pain - abdomen	1/2 (50%)	1	1/12 (8.3%)	1
Sore throat	0/2 (0%)	0	1/12 (8.3%)	1
Umbilical hernia	0/2 (0%)	0	2/12 (16.7%)	2
Vomiting	0/2 (0%)	0	1/12 (8.3%)	1
General disorders
Cough	0/2 (0%)	0	1/12 (8.3%)	1
Headache	0/2 (0%)	0	1/12 (8.3%)	2
Hypertension	0/2 (0%)	0	2/12 (16.7%)	2
Pain - unspecified	0/2 (0%)	0	1/12 (8.3%)	1
Hepatobiliary disorders
Ascites	0/2 (0%)	0	2/12 (16.7%)	2
Infections and infestations
Streptococcal pharyngitis	0/2 (0%)	0	1/12 (8.3%)	1
Investigations
Leukopenia	0/2 (0%)	0	1/12 (8.3%)	1
Thrombocytopenia	0/2 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
Diplopia	0/2 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Runny nose	0/2 (0%)	0	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Bruising	0/2 (0%)	0	1/12 (8.3%)	2
Injection site reaction	1/2 (50%)	4	5/12 (41.7%)	15
Pain - axilla	0/2 (0%)	0	1/12 (8.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.