EBV-related diseases Infections and Infestations Infectious mononucleosis
Conditions
Interventions
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 aft
Sponsors
Vectorite Biomedica Inc. (Taiwan)
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
China
Outcome results
None listed