Pre-emptive treatment of epstein-barr virus (EBV)-associated lymphoproliferative disorder (LPD) and post-transplantational lymphoproliferative disorder (PTLD) with EBV-specific immune effector cell (EBV-IE)

ISRCTN ISRCTN26640234
DOI https://doi.org/10.1186/ISRCTN26640234
Secondary identifying numbers N/A
Submission date
05/03/2009
Registration date
13/03/2009
Last edited
13/03/2009
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Li-Min Huang
Scientific

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

Study information

Study designInterventional phase I/II single-arm single-centre trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleEpstein-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)
Study objectivesEpstein-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(s)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
Health condition(s) or problem(s) studiedEBV-related diseases
InterventionThe 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 typeDrug
Pharmaceutical study type(s)
PhasePhase I/II
Drug / device / biological / vaccine name(s)EBV-specific immune effector cells
Primary outcome measurePatients' 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 measuresTo 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 study start date01/05/2009
Completion date01/05/2011

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants12
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment01/05/2009
Date of final enrolment01/05/2011

Locations

Countries of recruitment

  • China
  • Taiwan

Study participating centre

College of Medicine and College of Public Health
Taipei
100
Taiwan

Sponsor information

Vectorite Biomedica Inc. (Taiwan)
Industry

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

Website http://www.vectorite.com
ROR logo "ROR" https://ror.org/00mjfwd15

Funders

Funder type

Industry

Vectorite Biomedica Inc. (Taiwan)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan