Human herpes virus (HHV) specific immune effector (IE) cell therapy for HHV-related diseases

ISRCTN	ISRCTN44627941
DOI	https://doi.org/10.1186/ISRCTN44627941
Protocol serial number	N/A
Sponsor	America Yuva Biomed Inc. (China)
Funders	Current sources of funding as of 02/07/13:, America Yuva Biomed Inc. (China), Previous sources of funding:, Vectorite Biomedica Inc. (Taiwan)

Submission date: 05/02/2009
Registration date: 27/02/2009
Last edited: 01/09/2020

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 Daopei Lu
Scientific

Shanghai Dap-Pei Hospital
Minhang County
Shanghai
201100
China

Study information

Primary study design	Interventional
Study design	Phase I/II trial, non-blind, single-site, single-group (compared with historical database) study
Secondary study design	Non randomised controlled trial
Study type	Participant information sheet
Scientific title	Human herpes virus (HHV) specific immune effector (IE) cells for prevention and treatment of HHV-related diseases
Study objectives	Human herpes viruses, including Epstein-Barr virus (EBV), cytomegalovirus (CMV) and HHV type 6 (HHV6) are common pathogens in humans. In healthy individuals, HHV infection is often self-resolved. However, in immune compromised individuals such as transplant patients, or young and elderly individuals, HHV-related diseases can be lethal. The development of an effective immune response is the best solution to treating HHV diseases. We hypothesise that HHV-specific immune effector cells can be used to prevent or cure HHV infections including EBV-associated lymphomas. Such immune effector cells can come from the recipients own blood, or their allogeneic transplant donors' blood. HHV-specific immune effector (IE) cells will be generated in culture and infused into patients. The safety of this approach, and virus titre and HHV-associated diseases will be closely monitored. The study will determine if HHV-specific IE cells can be used to prevent HHV infections and treat HHV-related diseases.
Ethics approval(s)	Institutional Review Board of Shanghai Dao-Pei Hospital, Institute of Hematology, Fu Dan University gave approval on the 10/05/07 (ref: SHDP-2007-0510)
Health condition(s) or problem(s) studied	Human herpes virus (HHV) infections
Intervention	The trial enrols paediatric and adult patients with potential of developing HHV-related diseases to receive immune cell infusions. 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 HHV-specific immune effector cells after haematopoietic stem cell transplantation, 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 previous sponsor for this trial (up to 02/07/2013) was: Vectorite Biomedica Inc. WR-09, 17th Fl 3 Yuan Qu Street Taipei 001 Taiwan
Intervention type	Drug
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	EBV-specific immune effector cells
Primary outcome measure(s)	1. Patients' immediate clinical response after IE cell infusion, i.e. body temperature and symptoms related to GvHD 2. Virus titre or DNA copy in blood or tissue biopsy 3. HHV-associated diseases such as EBV-associated post-transplant lymphoproliferative disorder (PTLD) 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.
Key secondary outcome measure(s)	1. Production: IE cell preparation success rate - the minimal IE cell number can be generated per subject 2. Efficacy: 2.1. Tracking HHV titre or copy number 2.2. HHV 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 HHV titre will be monitored 2.5. Survival rate and the time required to recover completely from HHV diseases 3. Prevention: determine the time and frequency of HHV 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 respose 4.3. Changes in biochemical parameters 4.4. Complete blood count (CBC) 4.5. SGPT (aspartate aminotransferase [AST]), SGOT (alanine aminotransferase [ALT]), total bilirubin, gamma-glutamyl transferase (g-GT) 4.6. Creatinine, blood urea nitrogen (BUN), uric acid 4.7. Physical response 4.8. Life sign changes 4.9. Blood pressure 4.10. Pulse 4.11. 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.
Completion date	25/06/2015

Eligibility

Participant type(s)	Patient
Age group	Other
Sex	All
Target sample size at registration	300
Key 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 lymphoproliferative disease: e.g. donor is HHV sero-positive (human herpes virus viral capsid antigen immunoglobulin G positive [HHV VCA IgG+]) and recipient is HHV sero-negative (HHV VCA IgG-) at time of transplantation 1.1.2. The subject has history of human herpes virus-associated lymphoproliferative disorder (HHV-LPD) or HHV-related malignancy 1.1.3. The subject develops HHV diseases and not considered suitable for conventional treatment 1.1.4. The subject shows human herpes virus deoxyribonucleic acid (HHV 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. HHV reactivation 1.2. HHV-infected subjects: 1.2.1. Subject develops HHV LPD and not suitable for conventional treatment 1.2.2. The subject shows HHV 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. HHV reactivation 2. Aged less than or equal to 65 years, either sex 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 time of upper limit 4.2. Bilirubin less than or equal to 1.5 time of upper limit 4.3. Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 time of upper limit 4.4. Serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 time of upper limit 5. Donor condition: 5.1. No chemo- or radiation-therapy 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 criteria	1. Donor or recipient shows hepatitis C virus (HCV), human immunodeficiency virus (HIV) or tuberculosis (TB) positive 2. Recipient develops grade IV graft-versus-host disease (GvHD) 3. Recipient is albumin-intolerant 4. Recipient life expectancy less than 8 weeks 5. Recipient received alternative cell therapy within 30 days 6. Recipient is pregnant
Date of first enrolment	25/06/2007
Date of final enrolment	25/06/2015

Locations

Countries of recruitment

China

Study participating centre

Shanghai Dap-Pei Hospital

Shanghai
201100
China

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

01/09/2020: No publications found.