Condition category
Infections and Infestations
Date applied
05/03/2009
Date assigned
13/03/2009
Last edited
13/03/2009
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Li-Min Huang

ORCID ID

Contact details

College of Medicine and College of Public Health
Division of Infectious Diseases
Department of Paediatrics
National Taiwan University Hospital
7 Chung-Shan South Road
Taipei
100
Taiwan

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Epstein-barr virus (EBV)-specific immune effector cell (EBV-IE) for pre-emptive/preventive and therapeutic treatment of EBV-related diseases such as lymphoproliferative disorder (LPD) and post-transplantation lymphoproliferative disorder (PTLD)

Acronym

Study hypothesis

Epstein-barr virus (EBV) is a common human pathogen. In healthy individuals, EBV infection is often self-resolved. However, in immune compromised individuals such as transplant patients, or young and elderly individuals, EBV-related diseases can be lethal. The development of an effective immune response is the best solution to treating EBV diseases. We hypothesise that EBV-specific immune effector cells can be used to prevent or cure EBV-associated disorders including lymphomas. Such immune effector cells can come from the patient's own blood, or human leukocyte antigen (HLA)-matched donors' blood. EBV-specific immune effector (IE) cells will be generated in ex-vivo culture and infused into patients. The safety of this approach, and virus titre and EBV-associated diseases will be closely monitored. The study will determine if EBV-specific IE cells can be used to prevent EBV infections and treat EBV-related diseases.

Ethics approval

The 144th meeting of Research Ethics Committee of the National Taiwan University Hospital approved on the 14th November 2008 (ref: 200809044D); approved duration: 05/12/2008 - 04/12/2009

Study design

Interventional phase I/II single-arm single-centre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

EBV-related diseases

Intervention

The pre-emptive/preventive arm of treatment is a phase I/II trial, non-blind, single site, single group (compared with historical database) study, and the subjects will be followed up for one year after treatment. Each subject will receive four infusions of EBV-specific immune effector cells, with seven follow-ups: one week after the last infusion, one month thereafter for three months, and every three months thereafter until the end of the trial. The data collected in this trial will be compared with historical data.

Intervention type

Drug

Phase

Phase I/II

Drug names

EBV-specific immune effector cells

Primary outcome measures

Patients' immediate clinical response after IE cell infusion, e.g., body temperature and symptoms related to GvHD. In addition, virus titre or DNA copy in blood or tissue biopsy will be monitored.

Outcomes are measured at 24 hours, day 2, day 3, day 4, day 5, day 6, day 7, week 2, week 4, month 2, month 3, month 6 and year 1.

Secondary outcome measures

To evaluate the rate of successful EBV-IE generation and ability of EBV-IE for anti-EBV efficacy and EBV reactivation prophylaxis:
1. Production: IE cell preparation success rate - the minimal IE cell number can be generated per subject
2. Efficacy:
2.1. Tracking EBV titre or copy number
2.2. EBV IE cell function analysis in vitro and its correlation with in vivo effect
2.3. Effect on PTLD - for subjects with EBV-PTLD
2.4. Effect on mononucleosis - body temperature and EBV titer will be monitored
2.5. Survival rate and the time required to recover completely from EBV-related diseases (LPD, PTLD)
3. Prevention: determine the time and frequency of EBV-related disease incidence in subjects after the first IE cell infusion, in comparison to historically-documented uninfused subjects
4. Safety:
4.1. Adverse effect documentation
4.2. National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or above response
4.3. Changes in biochemical parameters:
4.3.1. Complete blood count (CBC)
4.3.2. SGPT (aspartate aminotransferase [AST]), SGOT (alanine aminotransferase [ALT]), total bilirubin, gamma glutamyl transferase (g-GT)
4.3.3. Creatinine, blood urea nitrogen (BUN), uric acid
4.4. Physical response
4.5. Life sign changes:
4.5.1. Blood pressure
4.5.2. Pulse
4.5.3. Temperature

Outcomes are measured at 24 hours, day 2, day 3, day 4, day 5, day 6, day 7, week 2, week 4, month 2, month 3, month 6 and year 1.

Overall trial start date

01/05/2009

Overall trial end date

01/05/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. The participants should meet at least one of the following conditions:
1.1. Bone marrow transplant (BMT) or solid organ transplant (SOT) patient:
1.1.1. High-risk subject of developing LPD: donor is EBV sero-positive (EBV-VCA IgG+) while subject is EBV sero-negative (EBV-VCA IgG-)
1.1.2. The subject has history of EBV-LPD or EBV-related malignancy
1.1.3. The subject with EBV-LPD and is not adaptable for conventional treatment
1.1.4. The subject shows EBV DNA greater than or equal to 1000 genome copies/µg in the peripheral blood (with or without LPD) in two consecutive samplings (24 hours apart)
1.1.5. The subject with the symptoms of EBV reactivation (fever, diarrhoea or lymphadenopathy) and confirmed by biopsy examination, regardless of the EBV level
1.2. EBV-infected subjects without BMT/SOT:
1.2.1. Subject develops EBV-LPD and not suitable for conventional treatment
1.2.2. The subject shows EBV DNA greater than or equal to 1000 genome copies/µg in the peripheral blood (with or without LPD) in two consecutive samplings (24 hours apart)
1.2.3. The subject with the symptoms of EBV reactivation (fever, diarrhoea or lymphadenopathy) and confirmed by biopsy examination, regardless of the EBV level
2. Aged less than or equal to 65 years old
3. Subject blood:
3.1. White blood cell count (WBC) greater than or equal to 3500/µl
3.2. Blood lymphocytes greater than or equal to 750/µl
4. Liver and kidney function:
4.1. Creatinine less than or equal to 1.25 times of upper limit
4.2. Bilirubin less than or equal to 1.5 times of upper limit
4.3. Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 times of upper limit
4.4. Serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 times of upper limit
5. Donor condition:
5.1. No chemo- or radiotherapy within 4 weeks of blood collection; no steroid use within 1 week of blood collection
5.2. WBC greater than or equal to 3500/µl
5.3. Lymphocytes greater than or equal to 750/µl
6. Signed informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

12

Participant exclusion criteria

1. Donor or recipient is positive for hepatitis C virus (HCV) (HCV antibody), human immunodeficiency virus (HIV) (HIV antibody) or tuberculosis (TB) (TB culture)
2. Recipient develops grade IV graft-versus-host disease (GvHD)
3. Recipient is albumin-intolerant
4. Recipient life expectancy is less than 8 weeks
5. Recipient received alternative cell therapy within 30 days
6. Recipient is pregnant

Recruitment start date

01/05/2009

Recruitment end date

01/05/2011

Locations

Countries of recruitment

China

Trial participating centre

College of Medicine and College of Public Health
Taipei
100
Taiwan

Sponsor information

Organisation

Vectorite Biomedica Inc. (Taiwan)

Sponsor details

c/o Mr Mike Chen
WR-09
17th Fl.
3 Yuan Qu Street
Taipei
001
Taiwan

Sponsor type

Industry

Website

http://www.vectorite.com

Funders

Funder type

Industry

Funder name

Vectorite Biomedica Inc. (Taiwan)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes