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

Human herpes virus (HHV) specific immune effector (IE) cells for prevention and treatment of HHV-related diseases

Status

Active, not recruiting

Phases

Phase 1

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN44627941

Enrollment

300

Registered

2009-02-27

Start date

2007-06-25

Completion date

Unknown

Last updated

2020-09-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Human herpes virus (HHV) infections Infections and Infestations Herpesviral [herpes simplex] infections

Interventions

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, no

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 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

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
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.	—

Measure

Time frame

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.

—

Secondary

Measure	Time frame
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.	—

Measure

Time frame

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.

—

Countries

China

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026